Methods of dealkenylative amination and azidation

Abstract

The present disclosure relates to methods for dealkenylative amination. The present disclosure additionally relates to methods for dealkenylative azidation.

Description

Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO METHODS OF DEALKENYLATIVE AMINATION AND AZIDATION STATEMENT OF GOVERNMENT SUPPORT This invention was made with government support under GM141327 awarded by the National Institutes of Health. The government has certain rights in the invention. RELATED APPLICATIONS This application claims the benefit of priority to U.S. Provisional Patent Application No.63 / 534,466, filed August 24, 2023, the entire contents of which are incorporated herein by reference. BACKGROUND Great efforts have been directed toward alkene π-bond amination. In contrast, analogous functionalization of the adjacent C(sp2)–C(sp3) σ-bonds is much rarer. The increasing demand in medicinal research for more complex three-dimensional architectures and optically active amines has driven efforts to develop diverse practical methods for C(sp3)–N bond construction. Conventionally, the electron-rich nature of amino nitrogen atoms renders them strong nucleophiles that can attack the polarized chemical bonds of alkyl halides, alcohol derivatives, and carbonyls, thereby forging new C(sp3)–N bonds. Engaging ubiquitous and nonpolar C–C bonds in C(sp3)–N bond construction is an intriguing strategy because such transformations can be used to modify molecular skeletons directly and, thereby, access conventionally challenging or inaccessible aliphatic amines. Classical methods for C–C bond amination, including the Lossen, Hofmann, Curtius, Beckmann, and Schmidt rearrangements, which typically rely on 1,2-migration of an alkyl / aryl group from carbon to nitrogen, have demonstrated their utility in the syntheses of bioactive molecules and in industrial manufacturing. For example, 5.5 million metric tons of caprolactam, a precursor to Nylon 6, are produced annually through the Beckmann rearrangement of cyclohexanone oxime. Although these classical transformations are powerful methods for accessing nitrogen insertion products, the sources of the C–C bonds are limited mostly to ketones and carboxylic acids, and the sources of nitrogen atoms are limited to those that insert one N atom, leaving room for incorporation of alternative, perhaps more ubiquitous, chemical functionalities as the sources of both the C–C and C–N bonds. Thus, there is an ongoing unmet need for methods of aminating C(sp2)–C(sp3) σ-bonds.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO SUMMARY In some aspects, the present disclosure relates to methods of making a nitrogenous compound, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine or an azide, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine or the azide through a second single bond in place of the alkene. BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 shows mechanistic studies of dealkenylative amination. (A) Comparison of different copper complexes. (B) Kinetic studies. (C) Proposed mechanism. *MeCN / MeOH (9:1, v / v) was used because complex 87 does not dissolve in MeCN. †2 mol% of 89 was used. 2 mol% of (CuCl + Et4NCl) was used. FIG. 2 shows UV–Vis absorption spectra in MeCN at 23 °C of (A) a 1:1 mixture of CuCl + Phen (0.2 mM), (B) [(Phen)2Cu][CuCl2] (88) (0.1 mM), and (C) [(Phen)2Cu]BF4(89) (0.1 mM). Phen = phenanthroline. FIG.3 shows UV–Vis absorption spectra in MeCN at 23 °C of (A) a 1:1:1 mixture of CuCl + PhthH + TEACl (10.0 mM), (B) a 1:1 mixture of CuCl + TEACl (10.0 mM), (C) a 1:1 mixture of CuCl + PhthH (10.0 mM), (D) a 1:1 mixture of PhthH + TEACl (10.0 mM), (E) CuCl (10.0 mM), (F) PhthH (10.0 mM), (G) TEACl (10.0 mM). PhthH = phthalimide; TEACl = tetraethylammonium chloride. FIG.4 shows variable time normal analysis (VTNA) to determine the reaction order of (CuCl+ Phen) on 32b generation. FIG. 5 shows VTNA to determine the reaction order of (CuCl+ Phen) on MeOAc generation. FIG.6 shows VTNA to determine the reaction order of phthalimide on 32b generation. FIG. 7 shows VTNA to determine the reaction order of phthalimide on MeOAc generation. FIG.8 shows VTNA to determine the reaction order of peroxide on 32b generation. FIG.9 shows VTNA to determine the reaction order of peroxide on MeOAc generation.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO FIG.10 shows VTNA to determine the reaction order of complex 89 on 32b generation (from 0.5 mol % to 4.0 mol %) using 2.0 mol % of (CuCl + TEACl). FIG. 11 shows VTNA to determine the reaction order of complex 89 on MeOAc generation (from 0.5 to 4.0 mol %) using 2.0 mol % of (CuCl + TEACl). FIG.12 shows VTNA to determine the reaction order of complex 89 on 32b generation (from 0 to 0.5 mol %) using 2.0 mol % of (CuCl + TEACl). FIG. 13 shows VTNA to determine the reaction order of complex 89 on MeOAc generation (from 0 to 0.5 mol %) using 2.0 mol % of (CuCl + TEACl). FIG.14 shows VTNA to determine the reaction order of (CuCl + Et4NCl) (from 2.0 to 4.0 mol %) on 32b generation using 2.0 mol % of [(Phen)2Cu]BF4. FIG.15 shows VTNA to determine the reaction order of (CuCl + Et4NCl) (from 2.0 to 4.0 mol %) on MeOAc generation using 2.0 mol % of [(Phen)2Cu]BF4. FIG.16 shows VTNA to determine the reaction order of (CuCl + Et4NCl) (from 1.0 to 2.0 mol %) on 32b generation using 0.5 mol % of [(Phen)2Cu]BF4. FIG.17 shows VTNA to determine the reaction order of (CuCl + Et4NCl) (from 1.0 to 2.0 mol %) on MeOAc generation using 0.5 mol % of [(Phen)2Cu]BF4. FIG.18 shows VTNA to determine the reaction order of phenanthroline (from 2.0 to 4.0 mol %) on 32b generation using 4.0 mol % of CuCl. FIG.19 shows VTNA to determine the reaction order of phenanthroline (from 2.0 to 4.0 mol %) on MeOAc generation using 4.0 mol % of CuCl. FIG.20 shows VTNA to determine the reaction order of phenanthroline (from 4.0 to 8.0 mol %) on 32b generation using 4.0 mol % of CuCl. FIG.21 shows VTNA to determine the reaction order of phenanthroline (from 4.0 to 8.0 mol %) on MeOAc generation using 4.0 mol % of CuCl. FIG.22 shows the reaction profile using 4.0 mol % of complex 89 in the absence and presence of chloride anions. FIG.23 shows the proposed mechanism with known reaction constants. FIG.24 shows mass spectral evidence of the peroxide H at 4 mol% CuCl. FIG.25 shows mass spectral evidence of the peroxide H at 2 mol% CuCl. FIG.26 shows diastereoselectivity of the delakenylative amination reaction.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS In some aspects, the present disclosure relates to methods of making a nitrogenous compound, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine or an azide, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine or the azide through a second single bond in place of the alkene. In some preferred embodiments, the first single bond and the second single bond are located in the same position of the sp3-hybridized carbon. In certain preferred embodiments, the oxidant is ozone. In some embodiments, the SET reagent comprises a first-row transition metal salt and a ligand, preferably a bidentate ligand. In representative embodiments, the ligand is selected from 1,10-phenanthroline, bathophenanthroline, 4,7-dimethoxy-1,10- phenanthroline, 3,5,6,8-tetrabromo-1,10-phenanthroline, 1,10-phenanthroline-5,6-dione, 4,4’- di-tert-butyl-2,2’-bipyridine, (1S,2S)-N1,N2-dimethylcyclohexane-1,2-diamine, 3,4,7,8- tetramethylphenanthroline, triphenylphosphine, 4,7-di(pyrrolidin-1-yl)-1,10-phenanthroline, 4,7-dichloro-1,10-phenanthroline, 3,8-dibromo-1,10-phenanthroline, 2,9-dimethyl-1,10- phenanthroline, 3,8-dimesityl-1,10-phenanthroline, 2,2'-bipyridine, 4,4'-dimethoxy-2,2'- bipyridine, (2E,3E)-N2,N3-dimesitylbutane-2,3-diimine, (2E,3E)-N2,N3-diphenylbutane-2,3- diimine, 2,6-bis((R)-4-phenyl-4,5-dihydrooxazol-2-yl)pyridine, (4S,4'S)-2,2'-(propane-2,2- diyl)bis(4-phenyl-4,5-dihydrooxazole), (4R,4'R)-2,2'-(propane-2,2-diyl)bis(4-phenyl-4,5- dihydrooxazole), and 1,2-bis(diphenylphosphino)ethane. In certain especially preferred embodiments, the ligand is 1,10-phenanthroline. In certain embodiments, the first-row transition metal salt is selected from FeCl2, FeBr2, FeSO4, CuCl, CuBr, CuI, CuOAc, Cu(MeCN)4BF4, Cu(MeCN)4PF6, Cu₂O, CuOTf, CuCl2, CuBr2, CuSO₄, CuO, Cu(OAc)2, Cu(acac)2 and Cu(OTf)2. In some embodiments, the first-row transition metal salt is selected from FeCl2, FeBr2, FeSO4, CuCl, CuBr, CuI, CuOAc, Cu(MeCN)4BF4, CuCl2, Cu(OAc)2, and Cu(OTf)2. In some preferred embodiments, the first-row transition metal salt is CuCl. In certain embodiments, the SET reagent is a transition metal complex (e.g., a copper complex.)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO In some preferred embodiments, contacting the starting compound with the oxidant is performed in a primary alcohol (e.g., methanol) solvent. In certain embodiments, the SET reagent is present in a substoichiometric (e.g., catalytic) quantity (e.g., about 1-50 mol% relative to the starting compound). In some embodiments, the SET reagent is present at a concentration of about 1 mol%, about 2 mol%, about 5 mol%, about 10 mol%, about 15 mol%, about 20 mol%, about 25 mol%, about 30 mol%, about 35 mol%, about 40 mol%, about 45 mol%, or about 50 mol%. In some preferred embodiments, the SET reagent is present at a concentration of about 20 mol%. In certain embodiments, the method is performed under an inert atmosphere (e.g., N2 or Ar). In some embodiments, contacting the starting compound with the oxidant is performed at about -50 ℃, about -60 ℃, about -70 ℃, about -80 ℃, or about -90 ℃. In certain embodiments, contacting the oxidized starting compound with the SET reagent is performed at about 15 ℃, about 20 ℃, about 25 ℃, about 30 ℃, about 40 ℃, about 50 ℃, or about 60 ℃. In some preferred embodiments, contacting the oxidized starting compound with the SET reagent is performed at ambient temperature. In certain embodiments, the starting compound is represented by Formula Ia:Ia or a salt thereof, wherein RA is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1is H, alkyl, deuteroalkyl (e.g., deuteromethyl), aryl, or heteroaryl; or RAand R1combine to form a cycloalkyl; and R2 is H, alkyl, or hydroxyalkyl. In certain embodiments, the starting compound is represented by Formula I: I or a salt thereof, whereinAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO RAis alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1is H, alkyl, or deuteroalkyl (e.g., deuteromethyl); or RAand R1combine to form a cycloalkyl; and R2 is H or hydroxyalkyl. In some preferred embodiments, R1 is deuteromethyl. In certain embodiments, the starting compound is represented by Formula Ib:Ib or a salt thereof. In certain embodiments, the starting compound is represented by Formula Ic:Ic or a salt thereof, wherein RX is alkyl (e.g., methyl), hydroxyl, halo (e.g., chloro, bromo, or fluoro), cycloalkyl (e.g., cyclohexyl), aminoalkyl, or amidoalkyl; X1 is NRZ or C(RB)(RC); RB or RC are each independently H or alkyl; or RB and R4 combine to form a heterocyclyl (e.g., epoxyl); or Rcand R4combine to form a heterocyclyl (e.g., epoxyl); R4 is H; R3 is alkyl (e.g., methyl); RZis H, alkyl, aryl, ester (e.g., tert-butyloxycarbonyl), or sulfonyl (e.g., tosyl); m1 is 0, 1, 2, 3 or 4; and n1 is 0, 1, 2, 3, 4, 5, 6, 7, or 8. In certain embodiments, RZis tert-butyloxycarbonyl. In other embodiments, RZis tosyl. In some embodiments, R3is methyl. In certain embodiments, RBand R4combine to form a heterocyclyl (e.g., epoxyl). In some embodiments, Rc and R4 combine to form a heterocyclyl (e.g., epoxyl). In some embodiments, RX is methyl. In other embodiments, RX is hydroxyl.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO In certain embodiments, the starting compound is represented by Formula Id:Id or a salt thereof, wherein n2 is 0, 1, 2, 3, 4, 5, 6, 7, or 8. In some embodiments, the starting compound is a terpene. In some preferred embodiments, the starting compound is (+ / - / ±)-isopulegol, (+ / - / ±)-β-pinene, (+ / - / ±)-sabinene, (+ / - / ±)-β-citronellol, (+ / - / ±)-sclareol, (+ / - / ±)-dihydromyrcenol, (+ / - / ±)-carveol, (+ / - / ±)- nootkatone, cis-(+ / - / ±)-limonene oxide, α-methylstyrene, or α-trideuteromethylstyrene. In certain embodiments, the starting compound is selected from:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOthereof. Methods of dealkenylative amination In some embodiments, the methods disclosed herein comprise: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine through a second single bond in place of the alkene. In certain embodiments, the method is represented by Scheme IIa:Scheme IIa wherein A is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1and R2are each independently H, aryl (e.g., phenyl), heteroaryl, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl); or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XAis the oxidant; XB is the SET reagent; andAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO XCis the amine, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene. In certain embodiments, the method is represented by Scheme II:Scheme II wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1 and R2 are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XAis the oxidant; XB is the SET reagent; and XC is the amine, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1 and R2 is the alkene. In some preferred embodiments, the method is represented by Scheme II:Scheme II wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl), preferably alkyl, more preferably heterocycloalkyl, most preferably cycloalkyl; R1and R2are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XAis ozone;Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO XBis a copper complex, preferably [(Phen)2Cu]+; and XC is the amine, preferably a phthalimide, most preferably 2´,3´-O-isopropylideneadenosine; wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene. In some embodiments, contacting the oxidized starting compound with the SET reagent is performed in a polar aprotic first solvent. In certain embodiments, the polar aprotic first solvent is selected from acetone, dimethylformamide, acetonitrile, dichloromethane, benzene, methanol, dimethyl sulfoxide, and tetrahydrofuran, or a combination thereof. In some preferred embodiments, the polar aprotic first solvent is acetonitrile. In certain embodiments, the amine is a primary amine. In other embodiments, the amine is a secondary amine. In some embodiments, the amine is represented by Formula II:II or a salt thereof, wherein RBis aryl, hetaryl, heterocyclyl, heterocyclylalkyl, alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), cycloalkyl(heteralkyl), or cycloalkyl(aralkyl); and RYis H, alkyl, heteralkyl, cycloalkyl, or cycloalkyl(alkyl), ester (e.g., tert-butyloxycarbonyl), or sulfonyl (e.g., tosyl); In some embodiments, RY is tert-butyloxycarbonyl. In certain embodiments, RY is tosyl. In some embodiments, the amine is a nucleoside. In certain such embodiments, the amine is adenosine, guanosine, 5-methyluridine, uridine, cytidine, 2ʹ-deoxyadenosine, 2ʹ- deoxyguanosine, thymidine, 2ʹ-deoxyuridine, or 2ʹ-deoxycytidine. In certain embodiments, the amine is selected from:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOAtty Docket No. UCH-38225 [UCLA 2024-032-2] WOMethods of dealkenylative azidation In some embodiments, the methods disclosed herein comprise: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an azide, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the azide through a second single bond in place of the alkene. In certain embodiments, the method is represented by Scheme Ia:Scheme Ia whereinAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO A is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1and R2are each independently H, aryl (e.g., phenyl), heteroaryl, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl); or R1and A combine to form a cycloalkyl or heterocyclylalkyl; XA is the oxidant; XBis the SET reagent; and XD is the azide, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene. In certain embodiments, the method is represented by Scheme I:Scheme I wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1 and R2 are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1and A combine to form a cycloalkyl or heterocyclylalkyl; XAis the oxidant; XB is the SET reagent; and XD is the azide, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1 and R2 is the alkene. In some preferred embodiments, the method is represented by Scheme I:Scheme IAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl), preferably alkyl, more preferably heterocycloalkyl, most preferably cycloalkyl; R1 and R2 are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XAis ozone; XB is a copper complex, such as [(Phen)2Cu]+; and XD is trimethylsilyl azide, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene. In certain embodiments, the methods disclosed herein further comprise contacting the oxidized starting compound with a photocatalyst. In some embodiments, the methods disclosed herein further comprise irradiating the oxidized starting compound after contacting the oxidized starting compound with the photocatalyst. In certain embodiments, the irradiating is performed at a wavelength from about 250 nm to about 1000 nm. In some embodiments, the irradiating is performed at a wavelength from about 450 nm to 495 nm. In certain preferred embodiments, the irradiating is performed with blue light. In certain embodiments, the photocatalyst is a transition metal photocatalyst. In some embodiments, the photocatalyst is an organic photocatalyst. In some embodiments, the photocatalyst is selected from a ruthenium photocatalyst, an iridium photocatalyst, a titanium photocatalyst, a cobalt photocatalyst, a tungsten photocatalyst, and a copper photocatalyst. In certain embodiments, the photocatalyst is an iridium photocatalyst selected from (Ir[dF(CF3)ppy]2(dtbpy))PF6, [Ir(dtbbpy)(ppy)2]PF6, tris[2-phenylpyridinato- C2,N]iridium(III), [Ir(dF(Me)ppy)2(dtbbpy)]PF6, [Ir{dFCF3ppy}2(bpy)]PF6, Ir(dFppy)3, [Ir(dFCF3ppy)2-(5,5′-dCF3bpy)]PF6, Ir(p-CF3-ppy)3, [Ir(ppy)2(dtbpy)]PF6, dichlorotetrakis(2- (2-pyridinyl)phenyl)diiridium(III), [Ir(p-F(Me)ppy)2-(4,4′-dtbbpy)]PF6, [Ir(dFppy)2(dtbbpy)]PF6, Ir(p-F-ppy)3, Ir(p-tBu-ppy)3, (Ir[Me(Me)ppy]2(dtbpy))PF6, Ir[p- F(t-Bu)-ppy]3. Ir[dF(t-Bu)-ppy]3, Ir[FCF3(CF3)ppy]2(dtbbpy)PF6, and Ir[dFFppy]2-(4,4′- dCF3bpy)PF6. In some preferred embodiments, the photocatalyst is [Ir(ppy)2(dtbpy)]PF6. In certain embodiments, the photocatalyst is present in a substoichiometric (e.g., catalytic) quantity (e.g., about 1-50 mol% relative to the starting compound). In someAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO embodiments, the photocatalyst is present at a concentration of about 1 mol%, about 2 mol%, about 5 mol%, about 10 mol%, about 15 mol%, about 20 mol%, about 25 mol%, about 30 mol%, about 35 mol%, about 40 mol%, about 45 mol%, or about 50 mol%. In some preferred embodiments, the photocatalyst is present at a concentration of about 1 mol%. In certain embodiments, contacting the oxidized starting compound with the SET reagent is performed in a polar aprotic second solvent. In some embodiments, the polar aprotic second solvent is selected from acetone, dimethylformamide, acetonitrile, dichloromethane, benzene, methanol, dimethyl sulfoxide, and tetrahydrofuran, or a combination thereof. In some preferred embodiments, the polar aprotic second solvent is acetone. In other preferred embodiments, the polar aprotic second solvent is acetonitrile, methanol, or a combination thereof. In certain embodiments, the azide is represented by Formula IV: IV or a salt thereof, wherein RV is a leaving group. In some embodiments, RVis silyl (e.g., trimethylsilyl, tert-butyldimethylsilyl, triisopropylsilyl). In some preferred embodiments, RVis trimethylsilyl. In certain embodiments, the present disclosure relates to compounds formed by the methods disclosed herein. Great efforts have been directed toward alkene π-bond amination. In contrast, analogous functionalization of the adjacent C(sp2)–C(sp3) σ-bonds is much rarer. Herein it is reported how ozonolysis and copper catalysis under mild reaction conditions enable alkene C(sp3)–C(sp2) σ-bond–rupturing cross-coupling reactions for the construction of new C(sp3)– N bonds, including amines as well as azides. This unconventional transformation may be used for late-stage modification of hormones, pharmaceutical reagents, peptides, and nucleosides. The method enables coupling of abundantly available terpenes and terpenoids with nitrogen nucleophiles to access artificial terpenoid-alkaloids and complex chiral amines. In addition, a commodity chemical, α-methylstyrene, can be applied as a methylation reagent to prepare methylated nucleosides directly from canonical nucleosides in one synthetic step. A mechanistic investigation implicates an unusual copper ion-pair cooperative process.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO The importance of aliphatic amines and nitrogen-heterocycles is evidenced by their wide representation in natural products, pharmaceuticals, agrochemicals, and other bioactive compounds. The increasing demand in medicinal research for more complex three-dimensional architectures and optically active amines has driven efforts to develop diverse practical methods for C(sp3)–N bond construction. Conventionally, the electron-rich nature of amino nitrogen atoms renders them strong nucleophiles that can attack the polarized chemical bonds of alkyl halides, alcohol derivatives, and carbonyls, thereby forging new C(sp3)–N bonds. Engaging ubiquitous and nonpolar C–C bonds in C(sp3)–N bond construction is an intriguing strategy because such transformations can be used to modify molecular skeletons directly and, thereby, access conventionally challenging or inaccessible aliphatic amines. Classical methods for C–C bond amination, including the Lossen, Hofmann, Curtius, Beckmann, and Schmidt rearrangements, which typically rely on 1,2-migration of an alkyl / aryl group from carbon to nitrogen, have demonstrated their utility in the syntheses of bioactive molecules and in industrial manufacturing. For example, 5.5 million metric tons of caprolactam, a precursor to Nylon 6, are produced annually through the Beckmann rearrangement of cyclohexanone oxime. Although these classical transformations are powerful methods for accessing nitrogen insertion products, the sources of the C–C bonds are limited mostly to ketones and carboxylic acids, and the sources of nitrogen atoms are limited to those that insert one N atom, leaving room for incorporation of alternative, perhaps more ubiquitous, chemical functionalities as the sources of both the C–C and C–N bonds.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOScheme 1. Concept and development of dealkenylative C(sp3)–N bond coupling. (A) Classic strategies in C(sp3)–N bond construction from carbonyl compounds and recent advances. (B) C(sp3)–N formation from alkene π-bonds. (C) C(sp3)–N formation from alkene σ-bonds. (D) Applications of dealkenylative C(sp3)–N bond coupling. SET = Single Electron Transfer.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOScheme 2. Application of dealkenylative C(sp3)–N bond coupling in bioactive compound synthesis. (A) Syntheses of complex chiral amines and bioactive compounds. (B) Methylation of nucleosides. (C) Terpene-nucleoside synthesis. *No flash column chromatography purification was necessary.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO In the past five years, several important advances have sought to address those limitations in the sources of both the C–C bonds and nitrogen atoms in C–C amination. The Jiao group employed the C–C bonds of alkylarenes, styrenes, and alkynylarenes in a Schmidt- type reaction, although the products were limited to anilines with new C(sp2)–N bonds, due to the preferred migration of the aryl group (Scheme 1A, eq.3). Fu, Hu, MacMillan, and Martin disclosed deconstructive C(sp3)–N couplings of carboxylic acid and ketone derivatives that overcame the limitation of 1,2-migration chemistry, providing methods to construct C(sp3)–N bonds with various N-heteroarenes, amides, and anilines (Scheme 1A, eq. 4). Despite these advances, there remains a huge scope for new sources of C–C bonds, beyond carbonyl compounds, for amination. In particular, developing methods to exploit a starting material’sAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO skeletal complexity to access chiral amine architectures would be highly desirable.Scheme 3. Substrate scope of nitrogen nucleophiles. Reactions were performed on 0.2–2.0 mmol scale using 20 mol% CuCl and 20 mol% phenanthroline (Phen) at 23 °C in MeCN. All yields are isolated yields. Absolute configurations are indicated by wedged and dashed bonds. *3 equiv. of alkene was used. †30 mol% of CuCl and 30 mol% of Phen wereAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO used. 2.5 equiv. of alkene was used. §5.0 equiv. of alkene was used. ¶The reaction was performed at 60 °C Alkenes are versatile functional groups that are abundant in natural products and industrial chemicals. In fact, C=C double bonds are the second most frequently encountered functional group in natural products (39.9%), exceeding ketone (15.9%) and carboxylic acid (10.6%) functionalities. Because chiral centers are common within natural products, it was surmised that the alkene moieties in natural products might serve as ideal C–C bond amination precursors for constructing complex chiral amines from naturally occurring chiral-pool molecules. Most methods for installing nitrogen groups to alkene motifs have focused on addition across the C–C π-bond to produce peripheral amination products (Scheme 1B). Conversely, the adjacent C(sp3)–C(sp2) σ-bonds have received less attention for C–N bond construction (Scheme 1C, top). It was envisioned that a C–N bond coupling strategy involving unusual C–C bond disconnections would constitute a distinct paradigm for alkyl amine synthesis, with several implications. First, it could access artificial terpenoid alkaloids and complex chiral amine architectures by embedding nitrogen motifs into the natural product precursors (Scheme 1D, top left). Second, a commodity chemical, α-methylstyrene, could be applied as an N-methylation reagent (Scheme 1D, top right; for comparison with other N- methylation reagents, see the Examples section). Third, such a tool could facilitate the generation of useful value-added compounds that have been challenging to form or inaccessible from readily available starting materials. One such example is (1R,2R,5R)-5-amino-2- methylcyclohexan-1-ol hydrogen chloride, a precursor of a JNK inhibitor. The significant step economy and cost savings from previous approaches indicate the potential utility of this C(sp3)–C(sp2) amination strategy in bioactive reagent synthesis (Scheme 1D, bottom). To accomplish the conversion of alkene C(sp3)–C(sp2) σ-bonds to C(sp3)–N bonds, we had to address a fundamental challenge: cleavage of a stronger alkene C(sp3)–C(sp2) σ-bond [bond dissociation energy (BDE) = 102 kcal / mol for propene] in preference to an aliphatic alkyl C(sp3)–C(sp3) σ-bond (90 kcal / mol in ethane). To realize it, this strategy engaged ozone, widely applied in several industries, to activate alkenes and facilitate their C(sp3)–C(sp2) σ- bond cleavages. Ozonolysis of alkenes in alcoholic solvents affords α-alkoxyhydroperoxides via the Criegee intermediate. The weakness of the O–O bond (44–46 kcal / mol for alkyl hydroperoxides) of an α-alkoxyhydroperoxide can serve as the energetic driving force to promote fragmentation of the robust C–C bond. Previously, Fe(II) salts were demonstrated toAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO serve as single-electron reducing agents to instigate O–O scission. The resulting α- alkoxyalkoxyl radical undergoes β-scission to release an alkyl radical that can be captured by organic radicophiles to provide the functionalization products of seemingly inert C(sp3)–C(sp2) σ-bonds (Scheme 1C, bottom). Copper is a redox-active metal that has been used for single electron reduction of peroxide intermediates in both biological processes and synthetic chemistry. Recent studies have demonstrated that copper catalysts are efficient at trapping alkyl radicals to afford C(sp3)– N bonds as reductive elimination products. It was envisioned sequential reduction of the hydroperoxide intermediate by a copper(I) amido complex and trapping of the resultant alkyl radical by the copper(II) center to induce reductive elimination and, thereby, form the C(sp3)– N bond in an overall redox-neutral process (Scheme 1C, bottom). To implement this design, the impact of the copper salt, ligand, and solvent were investigated. It was discovered that the aminodealkenylation could be performed efficiently under mild reaction conditions when employing CuCl (20 mol%) and 1,10-phenathroline (20 mol%) in acetonitrile (MeCN) at room temperature (see the Examples section for details). After determining the reaction conditions, a diverse array of nitrogen nucleophiles were assessed for dealkenylative C–N coupling with (–)-isopulegol as the model alkene substrate (Scheme 3). This protocol could be employed to install functionalized indoles (1–7) into (–)-isopulegol in high yields, producing enantiomerically pure indole derivatives that are promising scaffolds for drug development. Two indole-based natural products, the sleep hormone melatonin (6) and a protected form of the amino acid tryptophan (7), were alkylated in high yields with exclusive regioselectivity in the presence of secondary amide N–H bonds. Other pharmaceutically important substituted heterocyclic compounds, including azaindoles (8–10), indazoles (11 and 12), carbazole (13), pyrazoles (14 and 15), and pyrrole (16), were successfully coupled with (–)-isopulegol in good yields. 6-Chloro-7-iodo-7-deazapurine (17), a privileged scaffold in antitumor and antiviral drugs, was also a competent alkylation substrate. High yields were obtained when coupling it with phthalimide (18), and this process could be scaled (50 mmol) with a slightly decreased yield. In addition to azacycles, it was found that 2-aminopyrimidine (19), substituted anilines (20 and 21), and 2-aminopyridine (22) also underwent the dealkenylative C–N coupling efficiently. Less-nucleophilic amide (23) and sulfonamide (24) substrates also provided their coupling products in good yields. Notably, aryl halides wereAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO unaffected under the reaction conditions and might be employed as functional handles for further derivatization.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Scheme 4. Substrate scope of alkenes. All yields are isolated yields. For the detailed reaction conditions of each substrate, see the Supplementary Materials. Absolute configurations are indicated by wedged or dashed bonds, unless otherwise specified. The diastereoisomers were separated by flash column chromatography; major diastereoisomers are shown. *Wedged and dashed bonds indicate the relative stereochemistry, because the racemic starting material was used. Beyond (–)-isopulegol, an array of terpenes, terpenoids, and their derivatives were subjected to the deconstructive C–N coupling protocol to afford various artificial terpenoid alkaloids (Scheme 4). Most of these substrates are single enantiomers derived from natural products or are natural products themselves. (+)-Nootkatone and a eudesmane-type sesquiterpenoid underwent fragmentative C–N couplings with 3-chloroindazole and phthalimide to give the products 31a / 31b and 32a / 32b, respectively, in good yields with excellent diastereoselectivities. The bridged cyclic ketoester 33 was obtained in moderate yield and diastereoselectivity from the synthetic intermediate leading to (+)-seychellene. While good yields could be obtained regardless of substrate, the diastereoselectivity varied widely, especially when engaging the monocyclic terpenoids (–)-limonene-1,2-diol, (+)- dihydrocarvone ethylene glycol acetal, cis-(+)-limonene oxide, (+)-dihydrocarveol, (–)- perillyl alcohol oxide, (–)-carveol oxide, and (–)-O-benzoyl isopulegol (34–40). The observed diastereoselectivities are consistent with stereoselectivity trends commonly encountered in reactions with cyclic radicals, in which the stereoselectivity of the addition is dictated by a combination of torsional and steric effects. All of the diastereoisomers [except two: the diastereoisomers of the minor regioisomers, 57a and 57b, from the aminodealkenylation of (–)-β-pinene] were separable through silica-column flash chromatography—a particularly relevant feature for lead compound discovery because diastereoisomers often exhibit dramatically different bioactivities. Simple cyclohexyl and 4- piperidinyl radicals worked well when applied to the functionalization of melatonin (41) and tryptophan (42), respectively. Substrates bearing gem-disubstituted olefins, beyond the isopropenyl group, were evaluated in the reaction and it was found that they provided primary alkyl-substituted amines in a facile manner (43–47). The epoxy indazole 43 was obtained in 83% yield from a (±)-α-ionone oxide derivative. A (–)-sclareol–derived alkene underwent smooth dealkenylative amination with 3-chloroindazole to afford the drimane meroterpenoid derivative 44 in 61% yield. Drimane meroterpenoids possess diverseAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO bioactivities and this protocol provides a strategy toward N-heterocycles substituted with these terpenoid analogues. (R)-2,4-dimethylpent-4-en-1-ol was used, which can be accessed readily from Evans’ auxiliary (ca. $3 / g for R- or S-enantiomer) and 2-methallyl chloride, to synthesize (R)-3-(3-chloroindazolyl)-2-methylpropanol O-acetate (45), a precursor of muscarinic agonists, in 74% yield. Enantiopure 3-indazolyl-2-methylpropanols were prepared from the corresponding (+)- and (–)-3-bromo-2-methyl-1-propanols (ca. $190 / g from Sigma– Aldrich), which have previously been prepared from camphor sulfonic acids in five synthetic steps. Primary alkyl radicals from functionalized alkenes underwent efficient amination (46 and 47). Mono-substituted alkenes were also competent substrates for our Cu-catalyzed dealkenylative C–N coupling (R = R´ = H); in contrast, these alkenes performed only moderately in Fe(II)-mediated dealkenylative radical couplings. In the event, a 73% isolated yield of the dealkenylative C–N coupling product 48 was obtained from (±)-dihydromyrcenol. Mono-substituted alkenes derived from (–)-β-citronellol and (+)-geraniol oxide O-acetate derivatives afforded the fragmented C–N coupling products 49a, 49b, and 50 in good yields. 1-Decene, which is produced from the Ziegler process or through cracking in the petroleum industry, worked well as a substrate to generate 3-chloro-1-octylindazole (51) in 67% yield. It was found that an alkyl bromide, which could serve as a radical precursor, was tolerated under the reaction conditions to produce N-(4-bromobutyl)phthalimide (52) in 55% yield. Additionally, the deconstructive C–N coupling protocol was applied to the modification of molecules of interest to materials science. The vinyl groups of chiral molecules used in liquid crystals were replaced by 3-chloroindazole in good yields (53 and 54). Another natural product, phytol, containing a trisubstituted alkene unit, underwent regioselective C(sp3)–C(sp2) σ-bond cleavage to afford the coupling products 55a and 55b in good yields. Compounds 55a and 55b could be considered azacycle analogues of vitamin E, where the benzopyran unit is substituted by chloroindazole and phthalimide moieties, respectively. Alkylidenecycloalkanes were also suitable substrates for the dealkenylative C–N coupling process. (–)-β-Pinene provided the synthetically valuable chiral cyclobutanes 56a / 57a and 56b / 57b as 1.7:1 and 2.9:1 mixtures of regioisomers, respectively. In contrast, (±)-sabinene afforded the cyclopropane 58 as a single regioisomer in 78% yield. Methyleneadamantane (59) provided the equatorial amination product 60 exclusively. The β-amino acid derivative 62 was formed smoothly from the corresponding 4-methylenepiperidine 61. The copper-catalyzedAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO amination also converted the trisubstituted alkene 63 into the corresponding dealkenylated C– N coupling product 64 in 88% yield. The ability to use aminodealkenylation to install phthalimide units into chiral-pool molecules provided an opportunity to synthesize chiral primary amines. For example, the primary amine 65 was prepared in 75% yield from the phytol-derived phthalimide 55b. Chiral amino alcohols are common in nature, and such bioactive compounds often serve as auxiliaries in organic synthesis. 1,2-Aminocyclohexanol is an important motif in organic synthesis and medicinal chemistry; its unusual 5-methylated analogue 66 was prepared in 79% yield upon hydrazine-mediated deprotection of the phthalimide 18. Similarly, the aminocyclohexandiol 67 was synthesized from the opposite enantiomer of 34b (major diastereoisomer). Although 5- amino-3-methylpentan-1-ol is a useful building block, no asymmetric synthesis has been reported previously and its racemic form costs $965.90 / g. We obtained (R)-68 upon deprotection of the phthalimide 49b derived from (–)-β-citronellol. The chiral amino acid ester 69 can be synthesized from (–)-β-pinene. The abundant functional groups in terpenoids also facilitated the synthesis of more-elaborate amino alcohols through diversification. For example, the amino alcohol 71 was prepared from cis-(–)-limonene oxide through aminodealkenylation, thiolation, and deprotection. The amino alcohol 73, bearing a nootkatol skeleton, was obtained through the Luche reduction of 31b, followed by deprotection. The artificial indole alkaloid 75 was obtained through sequential Fischer indolization of 32b with 4-methoxylphenylhydrazine and deprotection. (1R,2R,5R)-5-Amino-2-methylcyclohexanol (77) is a synthetic intermediate leading to a JNK inhibitor (Scheme 1D); previous routes to its synthesis have involved 12 steps from (–)-limonene and 11 steps from the Diels–Alder reaction of isoprene and methyl acrylate. Using the deconstructive C–N coupling strategy with commercially available (–)- dihydrocarveol ($3.1 / g) and phthalimide, followed by deprotection using hydrazine monohydrate, afforded 77 in two steps in 54% overall yield. Chiral 4-substituted-1- methylcyclohexenes are synthetically challenging molecules and serve as key intermediates in the syntheses of various pharmaceuticals and natural products. (S)-1-Methylcyclohexenyl-4- amine (79, $1930.5 / g) has been a precursor in the synthesis of a trichodiene synthase inhibitor. The previous route to 79 involved eight steps from chiral limonenes. The enantioenriched phthalimide 78 was prepared recently by Liu and co-workers in four steps, including an alkene desymmetrization strategy employing a chiral cobalt(II) complex catalyst, which was prepared in six steps from L-alaninol. This strategy engaged commercially available cis-(–)-limoneneAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO oxide for dealkenylative amination. In the event, the C–N coupling products were produced in 83% yield with 2.1:1 d.r., with the desired diastereoisomer (isolated in 56% yield), after subsequent deoxygenation, affording the chiral phthalimide 78 in 55% yield. The deprotection proceeded smoothly to afford the primary amine 79 in 85% yield (29% overall yield over three steps). Considering the capability of copper-catalyzed coupling with various nucleophiles, this strategy might provide facile access to chiral 4-substituted-1-methylcyclohexenes. α-Methylstyrene (AMS), a by-product of the cumene process, is produced in over 292k tons annually. Because of the relative stability of the methyl radical (BDE: 105.0 kcal / mol for Me–H) over the phenyl radical (BDE: 112.9 kcal / mol for Ph–H), it was surmised that the Criegee ozonolysis product of AMS, upon exposure to the Cu(I) complex, should produce methyl radicals and, thereby, methylated amines. Indeed, it was found that reactions with AMS readily generated 1-methyl-3-chloroindazole (80) and caffeine (from theophylline) under this protocol, in yields of 84 and 67%, respectively. Zidovudine, an anti-HIV drug, was methylated at the N3 atom of the thymidine moiety to afford 3-methylzidovudine, without protecting the 5´-hydroxyl group. Particularly useful methylations were those of canonical nucleosides. N6- Methyladenosine (m6A) is the most abundantly modified nucleoside in eukaryotic mRNAs; it plays a crucial role in controlling gene expression in cellular, developmental, and disease processes. When using this protocol, adenosine ($0.097 / g) can be methylated directly to m6A ($103.4 / g) in 72% isolated yield in a single step, compared with the two or three steps in previous reports. Another common RNA modification, m6,6A ($148 / g), was obtained in nearly quantitative yield when using an additional equivalent of AMS (cf. the two steps in a previous report). The reaction was also performed on a 5-gram scale, providing a pure sample without the need for silica-column purification. The deuterium-labeled α-trideuteromethylstyrene (81), obtained from acetophenone and deuterium oxide in two steps, was used to generate isotopically labeled D3-m6A ($7030 / g). Other common methylated nucleosides, namely m6dA ($510 / g), m4C ($420 / g), and m4dC ($16.7 / mg), were prepared from the corresponding canonical deoxyadenosine, cytidine, and deoxycytidine, respectively, in good yields, where multiple synthetic steps or low yields were previously necessary. Encouraged by the successful nucleoside methylation, aminodealkenylation was employed for the rapid construction of terpene nucleosides. Terpene nucleoside natural products are generated through the adenosine processing of sesquiterpenoids or diterpenoids. They are found in bacterial metabolites and exhibit significant biofunctionality andAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO bioactivity—for example, as an antacid signaling molecule or as a component in the cell wall of mycobacterium tuberculosis. Furthermore, an adenosine-processed eudesmane-type sesquiterpenoid isolated from the myxobacterium Sorangium cellulosum exhibited moderate antibacterial activity against a wide range of bacterial strains. Pleasingly, the eudesmane-type sesquiterpenoid (82), (+)-nootkatone (83), drimane sesquiterpenoid (84), and the monoterpene (–)-isopulegol (85) were used to prepare terpene nucleosides in moderate to good yields. Analogues of terpene nucleosides can be applied as chemical probes of biological function, while their innate bioactivity might also provide a platform for developing lead compounds in medicinal research. Several experiments were conducted to gain insight into the reaction mechanism. Copper halides and phenanthroline are known to form tight ion pairs [(Phen)2Cu]+[CuX2]–instead of neutral complexes [(Phen)CuX] in solution, and our UV–Vis spectroscopic measurements indicated that the ion pair complex [(Phen)2Cu]+[CuCl2]–was the dominant species in MeCN (see the Examples section for details). Previous mechanistic studies have suggested that the neutral complex is the active species in the C–N coupling reaction, due to inefficient oxidative addition of ionic copper complexes to aryl halides. In contrast to oxidative addition, single electron transfer (SET) between hydroperoxide and either [(Phen)2Cu]+or [CuCl2]–is rapid (k = ca.4 × 103M–1s–1) and can trigger peroxide fragmentation. In attempts to directly probe the nature of the reactive copper species, a series of copper complexes were prepared (FIG. 1A) and their performance compared in the aminodealkenylation between (–)-dihydrocarveol and phthalimide. When the prototypical mixture of 1:1 CuCl and phenanthroline was replaced with a neutral phthalimido copper complex [(Phen)Cu(phth)] (86) or [(Phen)Cu(phth)2] (87), which had been proposed previously as a reactive intermediate, both the product yields (45 and 25%, respectively) and diastereoisomeric ratios (d.r.; 1.8:1.0 and 1.5:1.0, respectively) deteriorated significantly when compared with those of the standard reaction (90% NMR yield, 2.9:1.0 d.r.) (entries 1–3). Using the ion pair [(Phen)2Cu]+[CuCl2]–(88) directly afforded a reaction similar to the prototypical aminodealkenylation (87% yield, 2.8:1.0 d.r.), indicating that the ion pair might have been the active catalytic species. Reactions employing either [(Phen)2Cu]+(89) or [CuCl2]–(CuCl + Et4NCl) were extremely sluggish (entries 5 and 6), while the combination of independently prepared [(Phen)2Cu]+and [CuCl2]–afforded a product similar to that from the parent reaction (entries 4 and 7), but with a slightly diminished yield.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO To gain further insight into the mechanism of the copper-catalyzed amination, kinetic studies were conducted through variable time normalization analysis (VTNA). Using ReactIR, the concentration–time profiles were collected for both the C–C scission product [methyl acetate (MeOAc)] and the C–N coupling product (32b). The formation of MeOAc displayed 0.3-, zero-, and 1.3-order dependences with respect to S32-peroxide, phthalimide, and the catalyst (CuCl + Phen), respectively, while the coupling product 32b displayed 0.3-, 0.3-, and 1.3-order dependences. The zero– and pseudo-zero–order dependences on both peroxide and the amine imply that there existed an off-cycle catalyst resting state. Because both [(Phen)2Cu]+and [CuCl2]–are readily oxidized by peroxide, it was surmised that the resting states of the catalyst were the corresponding copper(II) species 91 and 93 (FIG.1C, eqs.1–3). The kinetic order of 1.3 with respect to catalyst indicates a scenario in which two catalytic species were operating on-cycle (Fig.1C). To tease out the roles of the cation and anion complexes in the catalytic cycle, we the kinetics of [(Phen)2Cu]+(89) and [CuCl2]–(1:1 mixture of CuCl + Et4NCl) were investigated separately. Both the C–C scission and C–N coupling events exhibited a kinetic order of 1.3 in [CuCl2]–in the presence of 2 mol% 89 (Fig.1B) and a kinetic order of 2 in the presence of 0.5 mol% 89. Moreover, although [CuCl2]–alone could catalyze the generation of MeOAc (Fig. 1B, iii), the formation of 32b was sluggish in the absence of [(Phen)2Cu]+(Fig. 1B, iv; Fig. 1A, entry 6). In sum, the C–C scission and C–N coupling steps displayed zero- and first-order dependences on [(Phen)2Cu]+at low concentrations (0.1–0.5 mmol%, Figs.1B, iii and v) and saturation kinetics at higher concentrations (0.5–2.0 mol%), respectively, each in the presence of 2.0 mol% [CuCl2]–. The amount of 89 did not affect C–C scission, generating MeOAc even in its absence (Fig.1B, iii), while both the production rate and yield of 32b were dependent on the concentration of 89 (Fig. 1B, iv). Complex 89 alone, however, could not generate significant amounts of MeOAc and 32b, both of which were generated steadily upon addition of Et4NCl (Fig. 1B, vi). It was surmised that [(Phen)2Cu]2+(93) was a stable cation whose reduction back to Cu(I) species was sluggish. Therefore, once [(Phen)2Cu]+was oxidized, the reaction stalled (Fig. 1C, eq. 3). Nevertheless, the addition of chloride replenished some Cu(II)ClmLn species that could oxidize the peroxide A and the radical B and return to the Cu(I) species (Fig. 5C, eqs. 1 and 2). The disparate reaction kinetics of [CuCl2]–and [(Phen)2Cu]+indicate that [CuCl2]–was involved in hydroperoxide decomposition, while [(Phen)2Cu]+Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO participated in the C–N coupling. Because C–C scission occurred prior to C–N coupling, [CuCl2]–influenced both the C–C scission and C–N coupling processes. Taken together, the results suggest the involvement of [CuCl2]––[(Phen)2Cu]+cooperative catalysis (Fig. 1C). SET between complex 90 and the peroxide A affords the alkoxyl radical E, which undergoes β-scission to generate the alkyl radical B. The cationic Cu(I) complex 92 is oxidized by peroxide A to afford a copper(II) complex 93. Deprotonated phthalimide associates with complex 93, followed by dissociation of Phen, to afford the phthalimido copper(II) complex 94. Complex 94 traps the alkyl radical B to afford the C–N coupling product and the copper(I) complex 97 through either an outer sphere (95) or inner sphere (96) pathway. Ligand exchange on the Cu(I) complex 97 affords 92. Subsequent electron transfer between 91 and 92 regenerates 90 and 93, completing a catalytic cycle. Alternatively, electron transfer between 97 and 91 is also possible to regenerate 90. Deprotonated phthalimide associates with the resulting Cu(II) complex from 97 to regenerate 94, completing the catalytic cycle. Given the straightforward nature of the modular introduction of nitrogen moieties through the unusual disconnection of alkene skeletons, the copper-catalyzed dealkenylative C–N coupling will find applications in the preparation of complex bioactive three- dimensional molecules and optically active amines of great interest in organic synthesis and medicinal chemistry. In one aspect, the present disclosure provides method of making a nitrogenous compound, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine through a second single bond in place of the alkene. In certain embodiments, the method is represented by Scheme I:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOScheme I wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1and R2are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XAis the oxidant; XBis the SET reagent; and XC is the amine, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene. This disclosure also includes all suitable isotopic variations of a compound or reagent of the disclosure. An isotopic variation of a compound or reagent of the invention is defined as one in which at least one atom is replaced by an atom having the same atomic number but an atomic mass different from the atomic mass usually or predominantly found in nature. Examples of isotopes that can be incorporated into a compound of the invention include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as2H (deuterium),3H (tritium),11C,13C,14C,15N,17O,18O,32P,33P,33S,34S,35S,36S,18F,36Cl,82Br,123I,124I,129I and131I, respectively. Accordingly, recitation of “hydrogen” or “H” should be understood to encompass(protium),2H (deuterium), and3H (tritium) unless otherwise specified. Certain isotopic variations of a compound of the invention, for example, those in which one or more radioactive isotopes such as3H or14C are incorporated, are useful in drug and / or substrate tissue distribution studies. Tritiated and carbon-14, i.e.,14C, isotopes are particularly preferred for their ease of preparation and detectability. Further, substitution with isotopes such as deuterium may afford certain therapeutic advantages resulting from greater metabolic stability, for example, increased in vivo half-life or reduced dosage requirements and hence may be preferred in some circumstances. Such variants may also have advantageous optical properties arising, for example, from changes to vibrationalAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO modes due to the heavier isotope. Isotopic variations of a compound of the invention can generally be prepared by conventional procedures known by a person skilled in the art such as by the illustrative methods or by the preparations described in the examples hereafter using appropriate isotopic variations of suitable reagents. Definitions Unless otherwise defined herein, scientific and technical terms used in this application shall have the meanings that are commonly understood by those of ordinary skill in the art. Generally, nomenclature used in connection with, and techniques of, chemistry, cell and tissue culture, molecular biology, cell and cancer biology, neurobiology, neurochemistry, virology, immunology, microbiology, pharmacology, genetics and protein and nucleic acid chemistry, described herein, are those well-known and commonly used in the art. The methods and techniques of the present disclosure are generally performed, unless otherwise indicated, according to conventional methods well known in the art and as described in various general and more specific references that are cited and discussed throughout this specification. See, e.g. “Principles of Neural Science”, McGraw-Hill Medical, New York, N.Y. (2000); Motulsky, “Intuitive Biostatistics”, Oxford University Press, Inc. (1995); Lodish et al., “Molecular Cell Biology, 4th ed.”, W. H. Freeman & Co., New York (2000); Griffiths et al., “Introduction to Genetic Analysis, 7th ed.”, W. H. Freeman & Co., N.Y. (1999); and Gilbert et al., “Developmental Biology, 6th ed.”, Sinauer Associates, Inc., Sunderland, MA (2000). Chemistry terms used herein, unless otherwise defined herein, are used according to conventional usage in the art, as exemplified by “The McGraw-Hill Dictionary of Chemical Terms”, Parker S., Ed., McGraw-Hill, San Francisco, C.A. (1985). All of the above, and any other publications, patents and published patent applications referred to in this application are specifically incorporated by reference herein. In case of conflict, the present specification, including its specific definitions, will control. As used herein, the terms “optional” or “optionally” mean that the subsequently described event or circumstance may occur or may not occur, and that the description includes instances where the event or circumstance occurs as well as instances in which it does not. For example, “optionally substituted alkyl” refers to the alkyl may be substituted as well as where the alkyl is not substituted. It is understood that substituents and substitution patterns on the compounds of the present disclosure can be selected by one of ordinary skilled person in the art to resultAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO chemically stable compounds which can be readily synthesized by techniques known in the art, as well as those methods set forth below, from readily available starting materials. If a substituent is itself substituted with more than one group, it is understood that these multiple groups may be on the same carbon or on different carbons, so long as a stable structure results. As used herein, the term “optionally substituted” refers to the replacement of one to six hydrogen radicals in a given structure with the radical of a specified substituent including, but not limited to: hydroxyl, hydroxyalkyl, alkoxy (e.g. methoxyl), halogen (e.g. fluorine or chlorine), alkyl (e.g. methyl, trifluoromethyl, ethyl, or isopropyl), alkenyl, alkynyl, aralkyl, heteroaralkyl, nitro, silyl, acyl, acyloxy, aryl, heteroaryl, cycloalkyl, heterocyclyl, amino, aminoalkyl, cyano, haloalkyl, haloalkoxy, -OCO-CH2-O-alkyl, -OP(O)(O-alkyl)2or –CH2- OP(O)(O-alkyl)2. Preferably, “optionally substituted” refers to the replacement of one to five hydrogen radicals in a given structure with the substituents mentioned above. More preferably, one to two hydrogen radicals are replaced by the substituents as mentioned above. It is understood that the substituent can be further substituted. As used herein, "alkyl" refers to a straight-chain or branched-chain aliphatic saturated hydrocarbon group, and may be preferably an alkyl having 1 to 6 carbon atoms, and more preferably an alkyl having 1 to 4 carbon atoms. Examples of such alkyls include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1- ethylpropyl, hexyl, isohexyl, 1,1-dimethyl butyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, and 2- ethylbutyl. The “alkyl” group may be optionally substituted. Moreover, the term “alkyl” as used throughout the specification, examples, and claims is intended to include both unsubstituted and substituted alkyl groups, the latter of which refers to alkyl moieties having substituents replacing a hydrogen on one or more carbons of the hydrocarbon backbone, including haloalkyl groups such as trifluoromethyl and 2,2,2-trifluoroethyl, etc. The term “acyl” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)-, preferably alkylC(O)-. The term “acylamino” is art-recognized and refers to an amino group substituted with an acyl group and may be represented, for example, by the formula hydrocarbylC(O)NH-. The term “acyloxy” is art-recognized and refers to a group represented by the general formula hydrocarbylC(O)O-, preferably alkylC(O)O-.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO The term “alkoxy” refers to an alkyl group having an oxygen attached thereto. Representative alkoxy groups include methoxy, ethoxy, propoxy, tert-butoxy and the like. The term “alkoxyalkyl” refers to an alkyl group substituted with an alkoxy group and may be represented by the general formula alkyl-O-alkyl. The term “Cx-y” or “Cx-Cy”, when used in conjunction with a chemical moiety, such as, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy is meant to include groups that contain from x to y carbons in the chain. C0alkyl indicates a hydrogen where the group is in a terminal position, a bond if internal. A C1-6alkyl group, for example, contains from one to six carbon atoms in the chain. The term “alkylamino”, as used herein, refers to an amino group substituted with at least one alkyl group. The term “alkylthio”, as used herein, refers to a thiol group substituted with an alkyl group and may be represented by the general formula alkylS-. The term “amide”, as used herein, refers to a group O R9N R10, wherein R9and R10each independently represent a hydrogen or hydrocarbyl group, or R9and R10taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure. The terms “amine” and “amino” are art-recognized and refer to both unsubstituted and substituted amines and salts thereof, e.g., a moiety that can be represented by, wherein R9, R10, and R10’ each independently represent a hydrogen or a hydrocarbyl group, or R9and R10taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure. The term “aminoalkyl”, as used herein, refers to an alkyl group substituted with an amino group. As used herein, "aryl" refers to a carbocyclic aromatic group that may be further fused with a second 5- or 6-membered carbocyclic group that may be aromatic, saturated or unsaturated, and examples of aryl may include, but are not limited to, phenyl, indanyl, 1-Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO naphthyl, 2-naphthyl, tetrahydronapthyl, and the like. Aryl may be linked to other groups at appropriate positions on the aromatic ring. Preferably the ring is a 5- to 7-membered ring, more preferably a 6-membered ring. Aryl groups include benzene, naphthalene, phenanthrene, phenol, aniline, and the like. The term “carbamate” is art-recognized and refers to a group, wherein R9and R10each independently represent hydrogen or a hydrocarbyl group. The term “carbocyclylalkyl”, as used herein, refers to an alkyl group substituted with a carbocycle group. The term “carbocycle” includes 5-7 membered monocyclic and 8-12 membered bicyclic rings. Each ring of a bicyclic carbocycle may be selected from saturated, unsaturated and aromatic rings. Carbocycle includes bicyclic molecules in which one, two or three or more atoms are shared between the two rings. The term “fused carbocycle” refers to a bicyclic carbocycle in which each of the rings shares two adjacent atoms with the other ring. Each ring of a fused carbocycle may be selected from saturated, unsaturated and aromatic rings. In an exemplary embodiment, an aromatic ring, e.g., phenyl, may be fused to a saturated or unsaturated ring, e.g., cyclohexane, cyclopentane, or cyclohexene. Any combination of saturated, unsaturated and aromatic bicyclic rings, as valence permits, is included in the definition of carbocyclic. Exemplary “carbocycles” include cyclopentane, cyclohexane, bicyclo[2.2.1]heptane, 1,5-cyclooctadiene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]oct-3-ene, naphthalene and adamantane. Exemplary fused carbocycles include decalin, naphthalene, 1,2,3,4-tetrahydronaphthalene, bicyclo[4.2.0]octane, 4,5,6,7-tetrahydro- 1H-indene and bicyclo[4.1.0]hept-3-ene. “Carbocycles” may be substituted at any one or more positions capable of bearing a hydrogen atom. The term “carbocyclylalkyl”, as used herein, refers to an alkyl group substituted with a carbocycle group. The term “carbonate” is art-recognized and refers to a group -OCO2-. The term “carboxy”, as used herein, refers to a group represented by the formula -CO2H.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO The term “cycloalkyl” includes substituted or unsubstituted non-aromatic single ring structures, preferably 4- to 8-membered rings, more preferably 4- to 6-membered rings. The term “cycloalkyl” also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is cycloalkyl and the substituent (e.g., R100) is attached to the cycloalkyl ring, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, pyrimidine, denzodioxane, tetrahydroquinoline, and the like. The term “ester”, as used herein, refers to a group -C(O)OR9wherein R9represents a hydrocarbyl group. The term “ether”, as used herein, refers to a hydrocarbyl group linked through an oxygen to another hydrocarbyl group. Accordingly, an ether substituent of a hydrocarbyl group may be hydrocarbyl-O-. Ethers may be either symmetrical or unsymmetrical. Examples of ethers include, but are not limited to, heterocycle-O-heterocycle and aryl-O-heterocycle. Ethers include “alkoxyalkyl” groups, which may be represented by the general formula alkyl-O-alkyl. The terms “halo” and “halogen” as used herein means halogen and includes chloro, fluoro, bromo, and iodo. The terms “hetaralkyl” and “heteroaralkyl”, as used herein, refers to an alkyl group substituted with a hetaryl group. As used herein, "heteroaryl" refers to a heteroaromatic compound containing at least one heteroatom selected from the group consisting of N, O and S, unless otherwise specified, and preferably the heteroaryl group may include, but are not limited to, a pyridine group, a pyrazine group, a pyrimidine group, a pyridazine group, a pyrazole group, an imidazole group, a triazole group, an indole group, an oxadiazole group, a thiadiazole group, a quinoline group, an isoquinoline group, an isoxazole group, an oxazole group, a thiazole group, and pyrrole group. The terms “heteroaryl” and “hetaryl” also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heteroaromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. Heteroaryl groups include, for example, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO The term “heteroatom” as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are nitrogen, oxygen, and sulfur. The term “heterocyclylalkyl”, as used herein, refers to an alkyl group substituted with a heterocycle group. As used herein, "heterocycle" refers to an aromatic or non-aromatic ring containing a heteroatom selected from a nitrogen atom, a sulfur atom and an oxygen atom other than a carbon atom as a ring member atom, and preferably includes a 4- to 10-membered and more preferably a 5- to 9-membered aromatic or non-aromatic ring containing 1 to 4 of the above heteroatoms. Examples of such aromatic rings include thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, triazolyl, tetrazolyl, triazinyl, and benzothiazolyl. In addition, examples of such non-aromatic rings include tetrahydrothienyl, tetrahydrofuranyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, oxazolinyl, oxazolidinyl, pyrazolinyl, pyrazolidinyl, thiazolinyl, thiazolidinyl, tetrahydroisothiazolyl, tetrahydrooxazolyl, tetrahydroisoxazolyl, piperidinyl, piperazinyl, tetrahydropyridinyl, dihydropyridinyl, dihydrothiopyranyl, tetrahydropyrimidinyl, tetrahydropyridazinyl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, azepanyl, diazepanyl, and azepinyl. The terms “heterocyclyl” and “heterocyclic” also include polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings wherein at least one of the rings is heterocyclic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls. As used herein, "arylene" and “heteroarylene” refer to divalent radicals of an aromatic ring and a heteroaromatic ring. The term “hydrocarbyl”, as used herein, refers to a group that is bonded through a carbon atom that does not have a =O or =S substituent, and typically has at least one carbon- hydrogen bond and a primarily carbon backbone, but may optionally include heteroatoms. Thus, groups like methyl, ethoxyethyl, 2-pyridyl, and even trifluoromethyl are considered to be hydrocarbyl for the purposes of this application, but substituents such as acetyl (which has a =O substituent on the linking carbon) and ethoxy (which is linked through oxygen, not carbon) are not. Hydrocarbyl groups include, but are not limited to aryl, heteroaryl, carbocycle, heterocycle, alkyl, alkenyl, alkynyl, and combinations thereof.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO The term “hydroxyalkyl”, as used herein, refers to an alkyl group substituted with a hydroxy group. The term “lower” when used in conjunction with a chemical moiety, such as, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy is meant to include groups where there are ten or fewer atoms in the substituent, preferably six or fewer. A “lower alkyl”, for example, refers to an alkyl group that contains ten or fewer carbon atoms, preferably six or fewer. In certain embodiments, acyl, acyloxy, alkyl, alkenyl, alkynyl, or alkoxy substituents defined herein are respectively lower acyl, lower acyloxy, lower alkyl, lower alkenyl, lower alkynyl, or lower alkoxy, whether they appear alone or in combination with other substituents, such as in the recitations hydroxyalkyl and aralkyl (in which case, for example, the atoms within the aryl group are not counted when counting the carbon atoms in the alkyl substituent). The term “phosphoryl” is art-recognized and refers to the group represented by the general formulawherein R9and R10each independently represent a negative charge, hydrogen, or hydrocarbyl. The term “phosphoramidityl” is art-recognized and refers to the group represented by the general formulawherein R9represents a negative charge, hydrogen, or hydrocarbyl; and each R10independently represents hydrogen or hydrocarbyl. The term “phosphoramidatyl” is art-recognized and refers to the group represented by the general formulawherein each R9and R10independently represent hydrogen or hydrocarbyl. The terms “polycyclyl”, “polycycle”, and “polycyclic” refer to two or more rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls, heteroaryls, and / or heterocyclyls) in which two or more atoms are common to two adjoining rings, e.g., the rings are “fused rings”. EachAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO of the rings of the polycycle can be substituted or unsubstituted. In certain embodiments, each ring of the polycycle contains from 3 to 10 atoms in the ring, preferably from 5 to 7. The term “sulfate” is art-recognized and refers to the group –OSO3H, or a pharmaceutically acceptable salt thereof. The term “sulfonamide” is art-recognized and refers to the group represented by the general formulae, wherein each R9and R10independently represents hydrogen or hydrocarbyl. The term “sulfoxide” is art-recognized and refers to the group–S(O)-. The term “sulfonate” is art-recognized and refers to the group SO3H, or a pharmaceutically acceptable salt thereof. The term “sulfone” is art-recognized and refers to the group –S(O)2-. The term “iminosulfanonyl” is art-recognized and refers to the group represented by the general formulawherein R9and R10each independently represents hydrogen or hydrocarbyl. In certain embodiments, as used herein, "substituent" includes a halogen group, a cyano group, a nitro group, a substituted or unsubstituted amino group including a substituted or unsubstituted alkyl group and a substituted or unsubstituted carboxyl group, a substituted or unsubstituted hydrocarbon group, substituted or unsubstituted heterocyclic group, acyl group, substituted or unsubstituted amino group, substituted or unsubstituted carbamoyl group, substituted or unsubstituted thiocarbamoyl group, substituted or unsubstituted sulfamoyl group, substituted or unsubstituted hydroxy group, a substituted or unsubstituted sulfonyl(SH) group, and a substituted or unsubstituted silyl group. The term “substituted” refers to moieties having substituents replacing a hydrogen on one or more carbons of the backbone. It will be understood that “substitution” or “substituted with” includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stableAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc. As used herein, the term “substituted” is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and non-aromatic substituents of organic compounds. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and / or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. Substituents can include any substituents described herein, for example, a halogen, a hydroxyl, a carbonyl (such as a carboxyl, an alkoxycarbonyl, a formyl, or an acyl), a thiocarbonyl (such as a thioester, a thioacetate, or a thioformate), an alkoxyl, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, a heterocyclyl, an aralkyl, or an aromatic or heteroaromatic moiety. It will be understood by those skilled in the art that the moieties substituted on the hydrocarbon chain can themselves be substituted, if appropriate. The term “thioalkyl”, as used herein, refers to an alkyl group substituted with a thiol group. The term “thioester”, as used herein, refers to a group -C(O)SR9or –SC(O)R9wherein R9represents a hydrocarbyl. The term “thioether”, as used herein, is equivalent to an ether, wherein the oxygen is replaced with a sulfur. The term “urea” is art-recognized and may be represented by the general formulaR9 R9, wherein R9and R10each independently represent hydrogen or a hydrocarbyl. Many of the compounds useful in the methods and compositions of this disclosure have at least one stereogenic center in their structure. This stereogenic center may be present in a R or a S configuration, said R and S notation is used in correspondence with the rules described in Pure Appl. Chem. (1976), 45, 11-30. The disclosure contemplates all stereoisomeric forms such as enantiomeric and diastereoisomeric forms of the compounds,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO salts, prodrugs or mixtures thereof (including all possible mixtures of stereoisomers). See, e.g., WO 01 / 062726. The term “silyl” is art-recognized and, as used herein, refers to a group having the general formula: wherein each R9independently represents H or hydrocarbyl, preferably alkyl or aryl. Illustrative examples of silyl groups include trimethylsilyl, tert-butyldimethylsilyl, and triisopropylsilyl. Furthermore, certain compounds which contain alkenyl groups may exist as Z (zusammen) or E (entgegen) isomers. In each instance, the disclosure includes both mixture and separate individual isomers. Some of the compounds may also exist in tautomeric forms. Such forms, although not explicitly indicated in the formulae described herein, are intended to be included within the scope of the present disclosure. The term “leaving group” is art-recognized and, as used herein, refers to an atom or group (charged or uncharged) that is detached from an atom in the residual or main part of the substrate during a reaction (e.g., a chemical reaction). For example, in the heterolytic solvolysis of benzyl bromide in excess acetic acid, the leaving group is Br-. Other illustrative examples of leaving groups include halides, tosylate (TsO-), mesylate (MsO-), and / or water. EXAMPLES The invention now being generally described, it will be more readily understood by reference to the following examples which are included merely for purposes of illustration of certain aspects and embodiments of the present disclosure and are not intended to limit the invention. Example 1: Preparation of Exemplary compounds Materials and Methods Unless otherwise stated, reactions were performed in flame-dried glassware fitted with rubber septa, under an argon atmosphere, and stirred with Teflon-coated magnetic stirring bars. Liquid reagents and solvents were transferred via syringe using standardAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO Schlenk techniques. Methanol (MeOH) was distilled over magnesium under an argon atmosphere. Dichloromethane (DCM), acetonitrile (MeCN), and triethylamine were distilled over calcium hydride under an argon atmosphere. Tetrahydrofuran (THF), benzene, toluene, and diethyl ether were distilled over sodium / benzophenone ketyl under an argon atmosphere. All other solvents and reagents were used as received from commercial sources, unless otherwise noted. Reaction temperatures above 23 °C refer to oil bath temperatures. Thin layer chromatography (TLC) was performed using SiliCycle silica gel 60 F-254 precoated plates (0.25 mm) and visualized under UV irradiation, with a cerium ammonium molybdate (CAM) stain or a potassium permanganate (KMnO4) stain. SiliCycle Silica-P silica gel (particle size 40–63 µm) was used for flash column chromatography (FCC).1H and13C NMR spectra were recorded using Bruker AV-500, AV-400, and AV-300 MHz spectrometers, with13C NMR spectroscopic operating frequencies of 125, 100, and 75 MHz, respectively. Chemical shifts (δ) are reported in parts per million (ppm) relative to the residual protonated solvent signal: CDCl3(δ = 7.26 for1H NMR; δ = 77.16 for13C NMR), CD3OD (δ = 3.31 for1H NMR; δ = 49.00 for13C NMR), DMSO-d6(δ = 2.50 for1H NMR; δ = 39.52 for13C NMR), CD2Cl2(δ = 5.32 for1H NMR; (δ = 53.84 for13C NMR), (CD3)2CO (δ = 2.05 for1H NMR; δ = 206.26, 29.84 for13C NMR), and CD3CN (δ = 1.94 for1H NMR; δ = 118.26, 1.32 for13C NMR). Data for1H NMR spectra are reported as follows: chemical shift, multiplicity, coupling constant(s) (Hz), and number of hydrogen atoms. Data for13C NMR spectra are reported in terms of chemical shift. The following abbreviations are used to describe the multiplicities: s = singlet; d = doublet; t = triplet; q = quartet; quint = quintet; m = multiplet; br = broad. Melting points (MP) are uncorrected and were recorded using an Electrothermal® capillary melting point apparatus. IR spectra were recorded using a Jasco FTIR4100 spectrometer with an ATR attachment; the selected signals are reported in unitsOptical rotations were recorded using an Autopol IV polarimeter and a 100-mm cell, at concentrations close to 1 g / 100 mL. HRMS (ESI) was performed using a Waters LCT Premier spectrometer equipped with an ACQUITY UPLC system and autosampler. HRMS (DART) was performed using a Thermo Fisher Scientific Exactive Plus spectrometer equipped with an IonSense ID-CUBE DART source. Ozonolysis was performed using a Globalozone GO-D3G (3 g / h) ozone generator (2.0 L / min, 50% power, O2feed gas). In situ FTIR spectroscopic reaction monitoring was performed using a Mettler Toledo ReactIR 702L apparatus, and the data were analyzed using iC IR 7.1 software.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Caution: Ozone is an extremely toxic and reactive oxidant that can react with some compounds to form explosive and shock-sensitive products. Reactions with ozone should be performed only by properly trained individuals in a well-ventilated fume hood (use of a blast- shield is also recommended, especially for reactions performed on larger scales). Exemplary Substrate Preparation The alkenes (–)-isopulegol, nootkatone, S36, S37, S48, S51, S52, S53, S54, phytol, (– )-β-pinene, and (±)-sabinene in Scheme S1, and the amines in Figs.2 and 3 and Figs.4B and 4C, were commercially available and used as received. Compounds S25 (59), S26 (60), S29 (61), S30 (61), S32 (62), S33 (63), S34 (64), S35 (65), S38 (66), S39 (67), S41 (68), S42 (69), S43 (70), S44 (70), S45 (71), S46 (72), S47 (72), S49 (73), S50 (73, 74), S59 (75), S61 (76), and S81 (77, 78) were synthesized according to the previously reported procedures (Scheme S1).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOScheme S1. Substrates used in aminodealkenylation reactions. Compounds S40 and 63 were prepared according to the following procedures.Benzoyl chloride (11.6 mL, 100 mmol, 1.25 equiv) was added slowly to a cooled (0 °C) mixture of (–)-isopulegol (12.3 g, 80.0 mmol, 1.0 equiv), triethylamine (13.2 mL, 100 mmol, 1.25 equiv), and N,N-dimethylpyridin-4-amine (0.980 g, 8.00 mmol, 0.1 equiv) in DCM (1 L). The resulting mixture was stirred at 0 °C for 30 min, then at room temperature overnight. ThisAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO mixture was washed with sat. aqueous NaHCO3(2 × 300 mL), sat. aqueous NH4Cl (2 × 300 mL), and brine (300 mL). The organic layer was dried (Na2SO4) and filtered. Evaporation of all volatiles under reduced pressure and purification through FCC (Rf= 0.83; hexanes / EtOAc, 9:1) yielded the benzoate S40 as a colorless oil (11.9 g, 53% yield). 1H NMR (400 MHz, CDCl3) δ 8.03–7.97 (m, 2H), 7.56–7.49 (m, 1H), 7.44–7.37 (m, 2H), 5.02 (td, J = 10.9, 4.4 Hz, 1H), 4.82–4.77 (m, 1H), 4.72 (p, J = 1.5 Hz, 1H), 2.35–2.25 (m, 1H), 2.21–2.11 (m, 1H), 1.81–1.70 (m, 2H), 1.70–1.68 (m, 3H), 1.68–1.57 (m, 1H), 1.53– 1.40 (m, 1H), 1.20–1.09 (m, 1H), 1.09–0.98 (m, 1H), 0.96 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 166.01, 146.16, 132.61, 130.89, 129.55, 128.23, 111.94, 74.32, 50.92, 40.51, 34.20, 31.45, 30.51, 22.07, 19.51. IR (neat, ATR): νmax3073, 2951, 2926, 2868, 1714, 1647, 1451, 1313, 1287, 1271, 1175, 1110, 1069, 1026, 975, 966, 890, 709 cm–1. HRMS (DART): [M+H]+calcd for [C17H23O2]+m / z 259.1693, found 259.1693. Optical Rotation:[α]25 D = –28.38 (c 0.39, CHCl3)The alkene 63 was synthesized according to the literature procedure (79). Methyl or ethyl diethylphosphonoacetate (1.23 g, 5.50 mmol, 1.1 equiv) was added to a cooled (0 °C) suspension of NaH (240 mg, 60 wt% in mineral oil, 6.00 mmol, 1.2 equiv) in THF (0.1 M). The resulting mixture was stirred at 0 °C for 30 min. A solution of 4,4-difluorocyclohexan-1- one (671 mg, 5.00 mmol, 1.0 equiv) in THF (10 mL) was added to the mixture, which was then stirred at room temperature until full conversion of the ketone was detected (TLC). The reaction was quenched through the addition of sat. aqueous NaHCO3 (100 mL) and then the aqueous phase was extracted with Et2O (2 × 100 mL). The combined organic layers were washed with brine, dried (Na2SO4), and filtered. Evaporation of all volatiles under reduced pressure and purification through FCC (Rf = 0.49; hexane / EtOAc, 20:1) yielded the enone product as a colorless oil (956 mg, 94% yield). DIBAL-H (1.2 M in toluene, 10 mL, 12 mmol) was added to a cooled (–78 °C) solution of the unsaturated ester (956 mg, 4.7 mmol) in THF (50 mL). When the reduction was complete (TLC), the reaction was quenched through the addition of water (2 mL) and sat. potassiumAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO sodium tartrate (10 mL) and stirring overnight. The suspension was filtered off and extracted with EtOAc (3 × 30 mL). The combined organic layers were dried (Na2SO4) and concentrated under reduced pressure. The crude material was purified through FCC on silica gel to afford 63 (Rf = 0.57; hexanes / EtOAc, 1:1) as a white solid (720 mg, 95% yield). 1H NMR (400 MHz, CDCl3) δ 5.48 (t, J = 6.9 Hz, 1H), 4.14 (d, J = 7.0 Hz, 2H), 2.39– 2.32 (m, 2H), 2.32–2.23 (m, 2H), 2.02–1.86 (m, 4H), 1.65 (brs, 1H). 13C NMR (100 MHz, CDCl3) δ 138.50, 123.57, 123.14 (t, J = 239.5Hz), 58.58, 34.79 (t, J = 23.6 Hz), 34.25 (t, J = 24.0 Hz), 32.09 (t, J = 5.3 Hz), 23.99 (t, J = 5.4 Hz). IR (neat, ATR): νmax 3343 (br), 2970, 2945, 2917, 2888, 2856, 1675, 1440, 1362, 1276, 1267, 1113, 1105, 1070, 1002, 965, 951, 931, 740, 678 cm–1. HRMS (DART): [M+Na]+calcd for [C8H12F2NaO]+m / z 185.0748, found 185.0721. M.p.: 32–35 °C. Reaction Optimization An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with phthalimide (44.1 mg, 0.300 mmol, 1.5 equiv), Cu(MeCN)4PF6(14.9 mg, 0.0400 mmol, 20 mol %), and 3,4,7,8-tetramethyl-1,10-phenanthroline L1 (14.2 mg, 0.0600 mmol, 30 mol %). The tube was purged with argon three times and then dry MeCN (2 mL) was added. This mixture was stirred at room temperature for 10 min. Another 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-O-benzoylisopulegol (S40, 258 mg, 1.00 mmol, 1.0 equiv) and MeOH (20 mL, 0.05 M), then cooled to –78 °C in a dry-ice / acetone bath. Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature and the MeOH evaporated in vacuo. The residue was dissolved in benzene (10 mL) and the solution concentrated in vacuo to remove the water. The residue was dissolved in MeOH (4.8 mL) to form a 0.2 M solution. A portion (1.0 mL) of this MeOH solution was transferred into the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 12 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.2 mmol, 1.0 equiv) as an internal standard. The reaction mixture concentrated in vacuo. The residue was passed through a short plug of silica gel to remove the copper salts and then the filtrate was concentrated in vacuo. The crude material was analyzed using NMR spectroscopy.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Scheme S2. Preliminary results and side products of copper-catalyzed aminodealkenylationAfter 12 h, the desired C–N coupling product 40 was obtained in 24% yield. Most of S40 had been consumed, with 16% recovery. Major byproducts were the ketone S40b, the alkane S40c, and the alkene S40d.1H NMR (400 MHz, CDCl3) δ 8.02–7.86 (m, 2H), 7.63–7.50 (m, 1H), 7.41 (t, J = 7.7 Hz, 2H), 5.23 (td, J = 11.0, 4.5 Hz, 1H), 2.74 (ddd, J = 12.6, 10.7, 3.8 Hz, 1H), 2.32–2.21 (m, 1H), 2.17 (s, 3H), 1.96 (dq, J = 13.4, 3.5 Hz, 1H), 1.87–1.72 (m, 1H), 1.71–1.63 (m, 1H), 1.49 (qd, J = 13.2, 3.7 Hz, 1H), 1.14–0.98 (m, 2H), 0.96 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 209.86, 165.57, 132.92, 130.29, 129.52, 128.33, 74.06, 55.82, 39.56, 33.42, 30.95, 29.03, 27.88, 21.86. HRMS (DART): [M+Na]+calcd for [C16H20NaO3]+m / z 283.1305, found 283.1305. IR (neat, ATR): νmax 3021, 2955, 2928, 2871, 2856, 1715, 1451, 1355, 1314, 1284, 1274, 1216, 1110, 1096 cm–1Optical Rotation:[α]25 D = –34.44 (c 0.3, CHCl3)1H NMR (400 MHz, CDCl3) δ 8.06–7.99 (m, 2H), 7.58–7.49 (m, 1H), 7.47–7.37 (m, 2H), 5.00–4.88 (m, 1H), 2.14–2.02 (m, 2H), 1.88–1.78 (m, 1H), 1.71–1.63 (m, 1H), 1.63–1.49Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO (m, 1H), 1.48–1.29 (m, 2H), 1.13 (q, J = 12.1 Hz, 1H), 0.96 (d, J = 6.6 Hz, 3H), 0.88 (qd, J = 12.7, 3.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 166.07, 132.66, 130.96, 129.52, 128.24, 73.87, 40.59, 34.08, 31.62, 31.40, 24.02, 22.33. IR (neat, ATR): νmax 2949, 2931, 2862, 1714, 1451, 1315, 1275, 1255, 1174, 1112, 1069, 1040, 1026, 972, 710 cm–1. HRMS (DART): [M+Na]+calcd for [C14H18NaO2]+m / z 241.1190, found 241.1190. Optical Rotation:[α]24 D = –4.05 (c 0.2, CHCl3)1H NMR (400 MHz, CDCl3) δ 8.15–7.97 (m, 2H), 7.60–7.49 (m, 1H), 7.48–7.37 (m, 2H), 5.89 (ddt, J = 9.5, 4.7, 2.1 Hz, 1H), 5.77–5.69 (m, 1H), 5.64 (dddq, J = 10.0, 5.8, 4.1, 2.1 Hz, 1H), 2.27–2.04 (m, 2H), 1.89 (dttt, J = 11.5, 9.2, 5.0, 2.7 Hz, 1H), 1.74 (dddd, J = 16.3, 10.2, 6.0, 2.8 Hz, 1H), 1.42 (td, J = 12.2, 9.8 Hz, 1H), 1.03 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 166.31, 132.79, 130.70, 129.60, 128.28, 126.90, 71.29, 36.83, 33.55, 27.86, 21.88. IR (neat, ATR): νmax3064, 3034, 2952, 2926, 2908, 2879, 2872, 2830, 1714, 1451, 1274, 1112, 1069, 1026, 953, 710 cm–1. HRMS (DART): [M+H]+calcd for [C14H17O2]+m / z 217.1223, found 217.1223. Optical Rotation:[α]24 D = 48.76 (c 0.43, CHCl3) A preliminary mechanistic explanation for the formation of the byproducts is provided below (Scheme S3). It was proposed that S40a was reduced by Cu(I) through single electron transfer (SET) to generate Int-A. Int-A is reduced again through another SET process to form Int-B. The ketone byproduct S40b is formed by the release of methoxide from Int-B. Int-A can also abstract a hydrogen atom to form Int-C, with subsequent hydrolysis affording S40b. Another possible pathway to the byproduct S40b is direct hydrolysis of S40a aided by Cu(I) and Cu(II) complexes as mild Lewis acids. It was proposed that the alkyl radical Int-D, generated from the alkoxyl radical Int-B through C–C bond scission, is trapped by a hydrogen atom donor to afford the alkane byproduct S40c. This alkyl radical (Int-D) can also be trapped by a Cu(II) species. Instead of C–N coupling, β-H elimination occurs to give then alkene S40d.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOScheme S3. Preliminary mechanistic explanation for the formation of the byproducts 3.2 Condition optimization Table 1. Survey of the reaction solventsEntry Solvent 12 (%) 1 MeCN / MeOH (2:1) 23 2 acetone / MeOH (2:1) 22 3 DMF / MeOH (2:1) 18 4 DMSO / MeOH (2:1) 23 5 THF / MeOH (2:1) 17 6 MeOH 18 7 MeCN 27 8 DMF < 5 9 DMSO < 5Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Procedure: An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with 3-chloroindazole (S12, 30.5 mg, 0.200 mmol, 1.0 equiv), tetrakis(MeCN)copper(I) tetrafluoroborate (12.6 mg, 0.0400 mmol, 20 mol %), and 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %). The tube was purged with argon three times and then a dry solvent (2 mL) was added to make Solution A. This mixture was stirred at room temperature for 10 min. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-isopulegol (154.3 mg, 1.0 mmol) and MeOH (5 mL, 0.2 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. For the experiments indicated in Table S1, entries 1–5, this solution was used directly: by transferring a portion (1.0 mL) of this hydroperoxide solution into Solution A in the Schlenk tube via syringe. For entries 6–9, the hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and concentrated in vacuo to remove adventitious water. The residue was dissolved in the corresponding solvents (4.8 mL) to give a 0.2 M solution of the hydroperoxide. A portion (1.0 mL) of this hydroperoxide solution was transferred into Solution A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 12 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv) as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 1: Screening was started by adding a MeOH solution of the peroxide directly into Solution A—an easier way to set up the reaction. It was found, however, that all of the reactions performed similarly, with poor yields (entries 1 to 5). Single solvents were then screened, and it was found that the reaction worked best in MeCN (entry 7). Although the product could be obtained when using DMF or DMSO as a co-solvent with MeOH, the single solvents afforded poor results. MeOH was the best solvent for the methylation of nucleosides.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Table 2. Survey of the copper saltsEntry Cu salt 12 (%)2 CuBr 46 3 CuI 44 4 CuOAc 49 5 Cu(MeCN)4BF427 6 CuCl228 7 Cu(OAc)2 30 8 Cu(OTf)2 trace Procedure: An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with 3-chloroindazole (S12, 30.5 mg, 0.200 mmol, 1.0 equiv), a copper salt (0.0400 mmol, 20 mol %), and 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %). The tube was purged with argon three times and then dry MeCN (2 mL) was added to make Solution A. This mixture was stirred at room temperature for 10 min. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-isopulegol (154.3 mg, 1.0 mmol) and MeOH (5 mL, 0.2 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. The hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and the solution concentrated in vacuo to remove adventitious water. The residue was dissolved in MeCN (4.8 mL) to form a 0.2 M solution of the hydroperoxide. A portion (1.0 mL) of this hydroperoxide solution was transferred into Solution A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 12 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 2: It was found that Cu(I) species needed an anionic ligand to neutralize the Lewis acidity. A cationic Cu(I) species [e.g., Cu(MeCN)4BF4] might afford a lower yield because it might promote hydrolysis of the hydroperoxide intermediate. A stronger Lewis acid [e.g., a Cu(II) species] also lowered the yield, and the use of Cu(OTf)2afforded the ketone byproduct in 90% yield. When using Cu(I), the reaction was very fast. For example, the reaction was finished within 1 min when using CuCl. In contrast, when using CuCl2, the reaction was slow (12 h, entry 6). Table 3. Survey of the ligandsAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO 7 L7 13 8 L8 52 9*L9 24 10*,†L10 7 11*L11 30 * Reaction was run for 12 h. † 0.08 mmol; 40 mol % ligand. Procedure: An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with 3-chloroindazole (S12, 30.5 mg, 0.2 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), and a ligand (0.0400 mmol, 20 mol %). The tube was purged with argon three times and then dry MeCN (2 mL) was added to make Solution A. This mixture was stirred at room temperature for 10 min. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-isopulegol (154.3 mg, 1.0 mmol) and MeOH (5 mL, 0.2 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. The hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and the solution concentrated in vacuo to remove adventitious water. The residue was dissolved in MeCN (4.8 mL) to form a 0.2 M solution of the hydroperoxide. A portion (1.0 mL) of this hydroperoxide solution was transferred into Solution A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 1 or 12 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv) as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 3: Phenanthroline, bipyridine, diamine, and phosphine ligands were tested. Phenanthroline and bipyridine ligands (L1, L2, L5, L8) worked well. The phenanthroline ligands bearing moderately electron-donating substituents (L1, L2, L5) afforded the best yields. Lower yields were obtained when using electron-rich or -poor phenanthroline ligands (L3, L4, L6, L7). The reactions were sluggish when using diamineAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO and phosphine ligands (entries 9–11). Although L1, L2, L5, and L8 exhibited similar reactivities for the coupling reactions between (–)-isopulegol and S12, their behaviors were different in the coupling reactions between (–)-dihydrocarveol and phthalimide (S18) (see Table S6). The simplest and least expensive ligand, 1,10-phenanthroline (L5), worked well in both reactions. Table 4. Survey of the alkene-to-amine ratiosEntry x Ratio 12 (%) (–)-isopulegol / S12 1 0.24 1.2 / 1 63 2 0.3 1.5 / 1 78 3 0.4 2 / 1 98 (92%isolated) 4*0.2 1 / 1.5 53 * 0.3 mmol of S12 was used. Procedure: An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with 3-chloroindazole (S12, 30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), and 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %). The tube was purged with argon three times before dry MeCN [2.8 mL (entry 1), 2.5 mL (entry 2), 2.0 mL (entry 3), or 3.0 mL (entry 4)] was added to make Solution A. This mixture was stirred at room temperature for 10 min. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-isopulegol (154.3 mg, 1.0 mmol) and MeOH (5 mL, 0.2 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. The hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and then the solution was concentrated in vacuo to remove adventitious water. The residue was dissolved in MeCN (4.8 mL) to form a 0.2 M solution ofAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO the hydroperoxide. A portion [1.2 mL (entry 1), 1.5 mL (entry 2), 2.0 (entry 3) mL, or 1.0 mL (entry 4)] of this hydroperoxide solution was transferred into Solution A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 1 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv) as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 4: The product yield increased upon increasing the amount of peroxide, while the amount of indazole had little effect. Table 5. Relationship between the Criegee ozonolysis and the overall product yieldHydroperoxide C–N coupling product Entry Alkene intermediates (%) (%) 1 1-decene 90 30 2 (–)-isopulegol 92 52 (–)-O-benzoyl 3 89 57 isopulegol Procedure: An oven-dried 25-mL round bottom flask equipped with a magnetic stirrer bar was charged with 3-chloroindazole (S12, 71.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (8.00 mg, 0.0800 mmol, 20 mol %), and 1,10-phenanthroline (14.40 mg, 0.0800 mmol, 20 mol %). The flask was purged with argon three times and then dry MeCN (4 mL) was added to make Solution A. This mixture was stirred at room temperature for 10 min.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with alkene (1.0 mmol) and MeOH (10 mL, 0.1 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. The hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and then the solution was concentrated in vacuo to remove adventitious water. The residue was dissolved in MeCN (9.8 mL) of form a 0.1 M solution of the hydroperoxide. A portion (4.0 mL) of this hydroperoxide solution was transferred into Suspension A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 1 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 0.5 equiv) as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 5: It was found that the regioselectivity for the Criegee ozonolysis of 1-decene was better than 4:1, providing the corresponding α-methoxyhydroperoxide in 90% yield. The yield of the C(sp3)–N coupling product was 30% when we used a 1:1 mixture of 1- decene and 3-chloroindazole. The yields for the α-methoxyhydroperoxides from (–)-isopulegol and (–)-O-benzoylisopulegol were 92 and 89%, respectively, while the C–N coupling yields using 3-chloroindazole were 52 and 57%, respectively. These results indicate that the yields of the C–N coupling products were not proportional to the observed amounts of the α- methoxyhydroperoxides. Also note that the typical reaction conditions employed 2 equiv of the alkene to consume all of the amine. In the experiments described above, limiting amounts of the alkene were employed to better gauge its influence on the overall yield of the reaction.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Table 6. Impact of ligands on diastereoselectivityEntry Ligand 72 (%) d.r. 1 L1 65 5.9:1 2 L2 85 3.0:1 3 L3 26 4.4:1 4 L5 90 2.9:1 5 L12 <5 N.D. 6 L13 86 2.7:1 7 L14 78 2.0:1 8 L15 87 2.8:1 9 L16 86 2.8:1 10 L17 44 2.7:1 11 L8 47 3.7:1 12 L18 37 6.8:1Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13 L19 <5 N.D. 14 L20 <5 N.D. 15 L21 <5 N.D. 16 L22 <5 N.D. 17 L23 <5 N.D. 18*L5 91 2.7:1 19*L1 74 5.4:1 * 20 mL of MeCN was used Procedure: An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with phthalimide (S18, 29.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), and a ligand (0.0400 mmol, 20 mol %). The tube was purged with argon three times and then dry MeCN (2 mL) was added to make Suspension A. This mixture was stirred at room temperature for 10 min. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-dihydrocarveol (154 mg, 1.0 mmol) and MeOH (5 mL, 0.2 M), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature. The hydroperoxide solution was concentrated in vacuo. The residue was dissolved in benzene (10 mL) and then the solution was concentrated in vacuo to remove adventitious water. The residue was dissolved in MeCN (4.8 mL) of form a 0.2 M solution of the hydroperoxide. A portion (2.0 mL) of this hydroperoxide solution was transferred into Suspension A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 1 h, followed by the addition of 1-chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv) as an internal standard. The reaction mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts and then the filtrate was concentrated in vacuo. The crude materials were analyzed using NMR spectroscopy. Summary of Table 6: All of the phenanthroline ligands afforded good yields (entries 1–9), except for the 1,8-dimethoxy– and 1,8-dipyrrolidinyl–substituted phenanthrolines (entries 3 and 5). The bipyridine ligands provided moderate yields. Yields of less than 5% were obtained when using diimine (entries 10–12) and bisoxazoline (entries 13–17) ligands.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Slightly better diastereoselectivities were obtained when using electron-rich phenanthrolines, compared with electron-poor phenanthrolines (L1 and L3 vs L13 and L14), but the yields diminished when using the electron-rich ones. As a result, although L5 afforded a lower d.r., the yield of the major diastereoisomer was the highest. Experimental Procedures and Characterization DataGeneral procedure A: An oven-dried 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with an N-nucleophile (0.20 mmol, 1.0 equiv), copper(I) chloride (4.0 mg, 0.040 mmol, 20 mol %), and 1,10-phenanthroline (7.2 mg, 0.040 mmol, 20 mol %). The flask was purged with argon three times and then dry MeCN (2.0 mL) was added. This mixture was stirred at room temperature for 10 min to make a Solution A or Suspension A. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with an alkene (0.40 mmol, 2.0 equiv) and MeOH (15 mL), then cooled to –78 °C in a dry- ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). If the alkene did not dissolve completely in MeOH, DCM / MeOH (ranging from 1:1 to 10:1) was used to dissolve the alkene at –78 °C. Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone, the reaction mixture was warmed to room temperature, and the MeOH was evaporated in vacuo. The residue was dissolved or suspended in benzene (10 mL) and then the solvent was evaporated in vacuo to remove adventitious water. The residue was redissolved in MeCN (1.0 mL) and transferred and kept in a syringe. The round-bottom flask was washed with MeCN (2 × 0.5 mL) and then the solutions were transferred, and kept, in the syringe to make Solution B. This MeCN solution of the hydroperoxide (Solution B) was added into the copper mixture (Solution A) via syringe. The reaction vessel was stirred at room temperature for a period of time ranging from 10 min to 12 h. Upon completion of the reaction (TLC), the reaction mixture was concentrated in vacuo. The residue was redissolved in DCM (5 mL) and silica gel (ca.4 g) was added. The mixtureAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO was carefully concentrated and then purified directly through silica gel column chromatography via dry load to afford the desired product. Note: This procedure was applied when the hydroperoxide displayed good solubility in MeCN. General procedure B: An oven-dried 10-mL round-bottom flask equipped with a magnetic stirrer bar was charged with an N-nucleophile (0.20 mmol, 1.0 equiv), copper(I) chloride (4.0 mg, 0.040 mmol, 20 mol %), and 1,10-phenanthroline (7.2 mg, 0.040 mmol, 20 mol %). The flask was purged with argon three times and then dry MeCN (2.0 mL) was added. This mixture was stirred at room temperature for 10 min to give Solution A. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with an alkene (2.0 equiv) and MeOH (15 mL), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). If the alkene did not dissolve completely in MeOH, DCM / MeOH (ranging from 1:1 to 10:1) was used to dissolve the alkene at –78 °C. Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved or suspended in benzene (10 mL) and then the solvent was evaporated in vacuo to remove adventitious water, followed by a purge with argon (three times). Acetonitrile (2 mL) was added to this residue to form a suspension (Suspension B). The MeCN solution of copper, ligand, and N-nucleophile (Solution A) was transferred into the hydroperoxide suspension (Suspension B) via syringe and washed with MeCN (2 × 0.5 mL). The reaction vessel was stirred at room temperature for 1–12 h. Upon completion of the reaction (TLC), the reaction mixture was concentrated in vacuo. The residue was redissolved in DCM (5 mL) and silica gel (ca.4 g) was added. The mixture was carefully concentrated and then purified directly through silica gel column chromatography via dry load to afford the desired product. Note: This procedure was applied when hydroperoxide did not fully dissolve in MeCN. Some greasy alkene substrates may need the use of DCM and MeOH as a co-solvent for ozonolysis and benzene as a co-solvent to prepare Suspension B. General procedure C: An oven-dried 10-mL round-bottom flask equipped with a magnetic stirrer bar was charged with copper(I) chloride (4.0 mg, 0.040 mmol, 20 mol %) andAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1,10-phenanthroline (7.2 mg, 0.040 mmol, 20 mol %). The flask was purged with argon three times and then dry MeCN (2 mL) was added. This mixture was stirred at room temperature for 10 min to give Solution C. Another 25-mL round-bottom flask equipped with a magnetic stirrer bar was charged with an alkene (2.0 equiv) and MeOH (15 mL), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). If the alkene did not dissolve completely in MeOH, DCM / MeOH (ranging from 1:1 to 10:1) was used to dissolve the alkene at –78 °C. Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the reaction mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved or suspended in benzene (10 mL) and then the solvent was evaporated in vacuo to remove adventitious water. The N-nucleophile (1.0 equiv) was added to this crude hydroperoxide residue. The flask was purged with argon three times and then dry MeCN (2 mL) was added (Suspension C). The MeCN solution of copper and ligand (Solution C) was added into this mixture of hydroperoxide and N-nucleophile (Suspension C) via syringe and washed with MeCN (2 × 0.5 mL). The reaction vessel was stirred at room temperature for 1–12 h. Upon completion of the reaction (TLC), the reaction mixture was concentrated in vacuo. The residue was redissolved in DCM (5 mL) and silica gel (ca.4 g) was added. The mixture was carefully concentrated and then purified directly through silica gel column chromatography via dry load to afford the desired product. Note: This procedure was applied when both the hydroperoxide and the N-nucleophile did not fully dissolve in MeCN. Catalyst loading: It was found that the optimal catalyst loading varied depending on both the nature of the alkene and amine starting materials. For example, while 30 mol% of catalyst was essential to obtain a high yield for the coupling reaction between isopulegol and lamivudine (compound 29), a mere 2 mol% of catalyst afforded a 73% yield of the product 32b when coupling the eudesmane-type sesquiterpenoid with phthalimide. It was found, in general, that a catalyst loading of 20 mol% was good for most of the substrates. Furthermore, 20 mol% of catalyst (4.0 mg of CuCl and 7.2 mg of phenanthroline) could be weighed more accuratelyAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO than 5 mol% (1.0 mg of CuCl). Consequently, 20 mol% of copper chloride and phenanthroline was adopted as the general amination condition. Procedures for a 50 mmol-Scale ReactionProcedure: An oven-dried 2-L round-bottom flask equipped with a magnetic stirrer bar was charged with phthalimide (7.36 g, 50.0 mmol, 1.0 equiv), copper(I) chloride (990 mg, 10.0 mmol, 20 mol %), and 1,10-phenanthroline (1.80 g, 20.0 mmol, 20 mol %). The flask was purged with argon three times and then dry MeCN (600 mL) was added. This mixture was stirred at room temperature for 10 min to give Solution A. Another 500-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-isopulegol (17.0 g, 110 mmol, 2.2 equiv) and MeOH (300 mL), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 10 min to expel excess ozone and then the reaction mixture was warmed to room temperature and the MeOH was evaporated in vacuo until approximately 70– 80 mL was left (for safety concerns, the concentration of the hydroperoxide solution should be less than 1.5 M). MeCN (230 mL) was added to the residue, followed by evaporation in vacuo until approximately 70–80 mL was left. Acetonitrile was added to the residue to make Solution B (330 mL). This MeCN solution of hydroperoxide (Solution B) was transferred into the copper mixture (Solution A) via cannula and rinsed with MeCN (2 × 35 mL). The reaction vessel was stirred at room temperature for 1.5 h. Upon completion of the reaction (TLC), the reaction mixture was concentrated in vacuo. The residue was redissolved in DCM (100 mL) and silica gel (ca.50 g) was added. The mixture was carefully concentrated and purified directly through silica gel column chromatography via dry load to afford the desired product (7.88 g, 61% yield) as a white solid. Details and Characterization Data of Substrates Shown in Scheme 1 and Scheme 4.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Prepared following General procedure A using 6-fluoro-1H-indole (27.0 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 1 (Rf = 0.38; hexanes / EtOAc, 4:1) as a white solid (45.8 mg, 93% yield). 1H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 8.7, 5.4 Hz, 1H), 7.14–7.10 (m, 2H), 6.88 (ddd, J = 9.5, 8.6, 2.3 Hz, 1H), 6.51 (d, J = 3.2 Hz, 1H), 3.99–3.78 (m, 2H), 2.10 (ddd, J = 12.8, 5.9, 4.0 Hz, 1H), 2.00 (ddt, J = 10.6, 4.2, 2.6 Hz, 1H), 1.87–1.79 (m, 2H), 1.72–1.60 (m, 1H), 1.30–1.10 (m, 2H), 1.03 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 159.79 (d, J = 236 Hz), 136.86 (d, J = 12 Hz), 124.81, 124.34 (d, J = 3 Hz), 121.59 (d, J = 10 Hz), 108.45 (d, J = 24 Hz), 102.51, 96.42 (d, J = 26 Hz), 73.03, 62.08, 42.10, 33.84, 31.15, 31.03, 21.83. HRMS (ESI-TOF): [M+H]+calcd for [C15H19FNO]+m / z 248.1445, found 248.1447. IR (neat, ATR): νmax 3425 (br), 3070, 2979, 2950, 2937, 2928, 2910, 2887, 2859, 1622, 1514, 1488, 1458, 1332, 1222, 1198, 1177, 1093, 1052, 1006, 933, 852, 803, 754, 716, 624, 529 cm–1. Optical Rotation: [α]27 D = 4.96 (c 1.0, CHCl3). M.p.: 170–171 °C.Prepared following General procedure A using 5-chloro-1H-indole (30.3 mg, 0.299 mmol, 1.0 equiv), copper(I) chloride (4.09 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 2 (Rf = 0.37; hexanes / EtOAc, 3:1) as a white solid (43.9 mg, 83% yield). 1H NMR (500 MHz, CDCl3) δ 7.57 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.18– 7.12 (m, 2H), 6.46 (d, J = 3.0 Hz, 1H), 3.97 (ddd, J = 12.0, 9.7, 4.2 Hz, 1H), 3.77 (ddd, J = 11.0, 9.7, 4.5 Hz, 1H), 2.09–2.02 (m, 1H), 2.02–1.95 (m, 1H), 1.86–1.78 (m, 2H), 1.76 (s, 1H), 1.70–1.60 (m, 1H), 1.25–1.11 (m, 2H), 1.02 (d, J = 6.6 Hz, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (125 MHz, CDCl3) δ 135.28, 129.31, 125.23, 121.90, 120.26, 110.93, 101.93, 73.22, 61.95, 42.08, 33.83, 31.13, 31.10, 21.83. HRMS (ESI-TOF): [M+H]+calcd for [C15H19ClNO]+m / z 264.1150, found 264.1161. IR (neat, ATR): νmax3397 (br), 2949, 2926, 2867, 2851, 1505, 1456, 1335, 1307, 1270, 1203, 1099, 1065, 1049, 1007, 937, 907, 868, 793, 753, 718 cm–1. Optical Rotation: [α]26 D = 8.57 (c 1.0, CHCl3) M.p.: 153–154 °C.Prepared following General procedure A using 7-chloro-1H-indole (30.3 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 3 (Rf= 0.36; hexanes / EtOAc, 4:1) as a colorless oil (25.5 mg, 48% yield). 1H NMR (400 MHz, CDCl3) δ 7.51 (dd, J = 7.8, 1.1 Hz, 1H), 7.26 (d, J = 3.0 Hz, 1H), 7.17 (dd, J = 7.6, 1.1 Hz, 1H), 7.00 (t, J = 7.7 Hz, 1H), 6.59 (d, J = 3.3 Hz, 1H), 5.30 (ddd, J = 12.1, 9.8, 4.0 Hz, 1H), 3.91 (td, J = 10.4, 4.4 Hz, 1H), 2.16 (ddt, J = 14.5, 7.1, 3.7 Hz, 2H), 1.79 (ddt, J = 12.9, 6.2, 3.4 Hz, 2H), 1.72–1.58 (m, 2H), 1.33–1.15 (m, 3H), 1.03 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 132.18, 131.57, 124.83, 124.25, 120.13, 119.89, 116.54, 103.44, 72.96, 61.82, 42.69, 33.71, 32.96, 31.26, 21.82. HRMS (DART): [M+H]+calcd for [C15H19ClNO]+m / z 264.1150, found 264.1150. IR (neat, ATR): νmax3623 (br), 3020, 2945, 1633, 1444, 1375, 1039, 919, 759 cm–1. Optical Rotation: [α]24 D = –21.67 (c 0.1, CHCl3)Prepared following General procedure A using 5-iodo-1H-indole (48.6 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthrolineAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 4 (Rf= 0.35; 15% EtOAc in hexanes) as a yellow solid (63.0 mg, 89% yield). 1H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 1.5 Hz, 1H), 7.44 (dd, J = 8.7, 1.7 Hz, 1H), 7.24 (t, J = 8.6, 1H), 7.13 (d, J = 3.2 Hz, 1H), 6.48 (d, J = 3.2 Hz, 1H), 3.99 (ddd, J = 12.0, 9.8, 4.3 Hz, 1H), 3.84 (td, J = 10.4, 4.4 Hz, 1H), 2.15–2.06 (m, 1H), 2.05–1.96 (m, 1H), 1.89–1.77 (m, 2H), 1.74–1.61 (m, 2H), 1.37–1.10 (m, 2H), 1.03 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 136.01, 130.94, 129.87, 129.76, 124.72, 111.92, 101.66, 82.98, 73.23, 61.92, 42.13, 33.84, 31.14, 31.09, 21.84. HRMS (ESI-TOF): [M+H]+calcd for [C15H19INO]+m / z 356.0506, found 356.0515. IR (neat, ATR): νmax 3393 (br), 2947, 2925, 2864, 2849, 1461, 1453, 1327, 1305, 1271, 1220, 1207, 1099, 1048, 1007, 937, 793, 773, 756, 753, 720, 485 cm–1Optical Rotation: [α]25 D = 9.83 (c 0.2, CHCl3) M.p.: 171–172 °C.Prepared following General procedure A using 5-(benzyloxy)-1H-indole-3- carbaldehyde (50.3 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. After 1 h, additional (–)-isopulegol (30.9 mg, 0.200 mmol, 1.0 equiv) was used to prepare Solution B and added into the reaction mixture. The crude product was purified through FCC to give 5 (Rf= 0.40; hexanes / EtOAc, 2:3) as a pale-yellow solid (68.2 mg, 94% yield). 1H NMR (500 MHz, CDCl3) δ 9.57 (s, 1H), 7.70 (d, J = 2.5 Hz, 1H), 7.65 (s, 1H), 7.50–7.44 (m, 2H), 7.42–7.35 (m, 3H), 7.35–7.29 (m, 1H), 7.00 (dd, J = 9.0, 2.6 Hz, 1H), 5.07 (s, 2H), 4.02 (ddd, J = 11.9, 9.7, 4.1 Hz, 1H), 3.94 (td, J = 10.4, 4.4 Hz, 1H), 2.84 (brs, 1H), 2.16–2.12 (m, 1H), 2.10–2.01 (m, 1H), 1.91–1.78 (m, 2H), 1.73–1.63 (m, 1H), 1.27 (td, J = 12.6, 10.7 Hz, 1H), 1.18 (qd, J = 12.0, 10.7, 5.3 Hz, 1H), 1.04 (d, J = 6.5 Hz, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (125 MHz, CDCl3) δ 184.34, 155.72, 137.25, 136.20, 133.03, 128.53, 127.86, 127.66, 125.88, 118.12, 114.91, 111.73, 104.51, 72.72, 70.41, 63.10, 42.67, 33.64, 31.25, 31.18, 21.76 HRMS (ESI-TOF): [M+H]+calcd for [C23H26NO3]+m / z 364.1907, found 364.1915. IR (neat, ATR): νmax 3373 (br), 3111, 3016, 2956, 2921, 2861, 1644, 1617, 1525, 1463, 1417, 1257, 1218, 1262, 1173, 1039, 1011, 748, 724, 696, 636 cm–1. Optical Rotation:[α]= –12.87 (c 0.5, CHCl3) M.p.: 88–89 °C.Prepared following General procedure A using melatonin (46.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 6 (Rf = 0.53; DCM / toluene / MeOH, 2:2:1) as a white solid (58.9 mg, 85% yield). 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J = 8.9 Hz, 1H), 6.99 (d, J = 2.7 Hz, 2H), 6.85 (dd, J = 8.9, 2.4 Hz, 1H), 5.91 (s, 1H), 3.96–3.84 (m, 5H), 3.59–3.45 (m, 2H), 2.89 (t, J = 6.7 Hz, 2H), 2.09 (d, J = 11.5 Hz, 1H), 2.00–1.96 (m, 1H), 1.90–1.70 (m, 5H), 1.68–1.61 (m, 1H), 1.26–1.09 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.41, 153.91, 132.49, 128.11, 122.78, 112.05, 111.96, 110.79, 100.61, 72.94, 61.89, 56.00, 42.32, 39.86, 33.92, 31.27, 31.18, 25.39, 23.21, 21.87. HRMS (ESI-TOF): [M+H]+calcd for [C20H29N2O3]+m / z 345.2173, found 345.2177. IR (neat, ATR): νmax3300 (br), 2926, 2869, 1649, 1552, 1485, 1454, 1372, 1235, 1218, 1179, 1097, 1049, 757 cm–1. Optical Rotation:[α]= 0.80 (c 0.5, CHCl3) M.p.: 68–70 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using methyl (tert-butoxycarbonyl)-L- tryptophanate (63.7 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 7 (Rf = 0.34; DCM / EtOAc, 9:1) as an off-white solid (77.3 mg, 90% yield). 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.20 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.10 (td, J = 7.4, 6.9, 0.9 Hz, 1H), 6.99 (s, 1H), 5.08 (d, J = 8.4 Hz, 1H), 4.70–4.54 (m, 1H), 4.00 (ddd, J = 12.0, 9.6, 4.2 Hz, 1H), 3.88 (td, J = 10.3, 4.3 Hz, 1H), 3.67 (s, 3H), 3.34–2.98 (m, 2H), 2.12 (d, J = 12.5 Hz, 1H), 2.07–1.90 (m, 2H), 1.82 (d, J = 12.7 Hz, 2H), 1.73–1.63(m, 1H), 1.41 (s, 9H), 1.30–1.11 (m, 3H), 1.03 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.82, 155.18, 137.04, 128.27, 122.78, 121.84, 119.45, 118.96, 110.17, 110.00, 79.81, 77.28, 72.96, 61.88, 54.42, 52.24, 42.10, 33.91, 31.19 (overlap), 28.34, 21.89. HRMS (ESI-TOF): [M+Na]+calcd for [C24H34N2NaO5]+m / z 453.2360, found 453.2366. IR (neat, ATR): νmax3409 (br), 2949, 2936, 2867, 1740, 1704, 1505, 1462, 1439, 1366, 1278, 1249, 1222, 1261, 1166, 1053, 1015, 752, 740 cm–1. Optical Rotation: [α]25 D = 15.87 (c 1.0, CHCl3) M.p.: 94–96 °C.Prepared following General procedure A using methyl 1H-pyrrolo[2,3-b]pyridine (23.6 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO was used to make Solution B. The crude product was purified through FCC to give 8 (Rf= 0.65; hexanes / EtOAc, 1:2) as a white solid (30.9 mg, 67% yield). 1H NMR (400 MHz, CDCl3) δ 8.26 (dd, J = 4.4, 1.2 Hz, 1H), 7.89 (dd, J = 7.8, 1.6 Hz, 1H), 7.28 (d, J = 3.6 Hz, 1H), 7.04 (dd, J = 7.8, 4.8 Hz, 1H), 6.48 (d, J = 3.6 Hz, 1H), 4.59 (ddd, J = 12.3, 9.9, 4.3 Hz, 1H), 3.94 (td, J = 10.6, 4.5 Hz, 1H), 2.72 (brs, 1H), 2.19–2.08 (m, 1H), 2.04 (dq, J = 12.8, 3.8 Hz, 1H), 1.92 (qd, J = 12.8, 3.7 Hz, 1H), 1.81 (dp, J = 13.0, 3.4 Hz, 1H), 1.73–1.61 (m, 1H), 1.35–1.15 (m, 2H), 1.01 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 148.26, 142.48, 129.09, 125.01, 120.90, 115.93, 100.29, 73.39, 59.98, 43.10, 33.76, 31.20, 31.19, 21.86. HRMS (ESI-TOF): [M+H]+calcd for [C14H19N2O]+m / z 231.1492, found 231.1494. IR (neat, ATR): νmax3324 (br), 3113, 3095, 3049, 3017, 2947, 2909, 2865, 2848, 1595, 1573, 1511, 1459, 1429, 1416, 1354, 1306, 1272, 1215, 1119, 1098, 1054, 937, 897, 795, 770, 753, 725 cm–1. M.p.: 173–174 °C. Optical Rotation:[α]= 18.47 (c 1.0, CHCl3)Prepared following General procedure A using methyl 1H-pyrrolo[3,2-c]pyridine (118 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (29.7 mg, 0.300 mmol, 30 mol %), 1,10- phenanthroline (54.0 mg, 0.300 mmol, 30 mol %), and MeCN (10 mL) to make Solution A. (–)-Isopulegol (462.8 mg, 3.00 mmol, 3.0 equiv) was used for ozonolysis and MeCN (15 mL) was used to make Solution B. The crude product was purified through FCC to give 9 (Rf = 0.38; DCM / toluene / MeOH, 2:2:1) as a pale-yellow solid (204.0 mg, 89% yield). 1H NMR (500 MHz, CD3OD) δ 7.62 (s, 1H), 6.85–6.60 (m, 1H), 4.17 (q, J = 9.3 Hz, 1H), 3.94 (td, J = 10.6, 4.4 Hz, 1H), 2.13–2.05 (m, 1H), 2.03–1.91 (m, 2H), 1.86–1.78 (m, 1H), 1.78–1.66 (m, 1H), 1.31–1.19 (m, 2H), 1.03 (d, J = 6.5 Hz, 3H). 13C NMR (125 MHz, CD3OD) δ 140.83 (br), 137.32 (br), 127.67, 102.33 (br), 78.08, 71.85, 61.66, 43.12, 33.33, 31.00, 30.88, 20.83. HRMS (ESI-TOF): [M+H]+calcd for [C14H19N2O]+m / z 231.1492, found 231.1495. IR (neat, ATR): νmax3277 (br), 2948, 2926, 2867, 1604, 1473, 1450, 1320, 1208, 1055, 897, 772, 751, 728 cm–1.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Optical Rotation:[α]24 D = 20.33 (c 1.0, CHCl3) M.p.: 193–195 °C. Note: Some of the1H and13C NMR spectral signals of compound 9 were not evident. We characterized the O-acetate–protected product to confirm its structure.A 10-mL vial equipped with a magnetic stirrer bar was charged with 9 (30 mg, 0.13 mmol), pyridine (1 mL), and acetic anhydride (0.3 mL). The mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with EtOAc (10 mL) and washed with aqueous 1 M HCl (2 × 5 mL), sat. aqueous NaHCO3 (5 mL), and brine (5 mL). The organic layer was dried (Na2SO4) and concentrated. The residue was purified through silica gel column chromatography to afford 9-Ac (Rf = 0.47; EtOAc / Et3N / MeOH, 100:3:5) as a pale-yellow oil (20.5 mg, 58% yield). 1H NMR (400 MHz, CD3OD) δ 8.72 (s, 1H), 8.14 (d, J = 6.0 Hz, 1H), 7.56 (d, J = 6.1 Hz, 1H), 7.48 (d, J = 3.4 Hz, 1H), 6.65 (d, J = 3.4 Hz, 1H), 5.13 (td, J = 11.0, 4.6 Hz, 1H), 4.44 (ddd, J = 12.0, 10.4, 4.6 Hz, 1H), 2.20–2.01 (m, 3H), 1.85 (ddt, J = 15.6, 6.1, 2.5 Hz, 1H), 1.82–1.70 (m, 1H), 1.45 (s, 3H), 1.40–1.23 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CD3OD) δ 169.81, 142.17, 140.77, 138.36, 126.65, 125.35, 105.75, 101.55, 74.52, 58.05, 39.30, 32.99, 30.68, 30.31, 20.60, 19.04. HRMS (ESI-TOF): [M+H]+calcd for [C16H21N2O2]+m / z 273.1598, found 273.1597. IR (neat, ATR): νmax 2952, 2930, 2869, 1737, 1602, 1471, 1457, 1374, 1320, 1243, 1213, 1041, 1029, 892, 729 cm–1. Optical Rotation: [α]25 D = 51.50 (c 0.2, CH2Cl2)Prepared following General procedure A using methyl 1H-pyrrolo[3,2-b]pyridine (118 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (29.7 mg, 0.300 mmol, 30 mol %), 1,10- phenanthroline (54.0 mg, 0.300 mmol, 30 mol %), and MeCN (10 mL) to make Solution A. (–)-Isopulegol (462.8 mg, 3.00 mmol, 3.0 equiv) was used for ozonolysis and MeCN (15 mL)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO was used to make Solution B. The crude product was purified through FCC to give 10 (Rf= 0.41; EtOAc / Et3N / MeOH, 10:1:1) as a light-yellow solid (214.0 mg, 93% yield). 1H NMR (500 MHz, CDCl3) δ 8.32 (brs, 1H), 7.72 (d, J = 7.0 Hz, 1H), 7.29 (s, 1H), 7.04 (brs, 1H), 6.44 (brs, 1H), 4.03–3.83 (m, 2H), 3.28 (brs, 1H), 2.13 (d, J = 11.8 Hz, 1H), 2.03–1.93 (m, 1H), 1.93–1.78 (m, 2H), 1.74–1.59 (m, 1H), 1.25 (q, J = 12.2 Hz, 1H), 1.16 (qd, J = 13.1, 3.3 Hz, 1H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 127.92, 117.44, 102.73, 72.70, 62.63, 42.58, 33.82, 31.21, 30.97, 21.84. HRMS (ESI-TOF): [M+H]+calcd for [C14H19N2O]+m / z 231.1492, found 231.1491. IR (neat, ATR): νmax3139 (br), 2950, 2926, 2863, 1605, 1507, 1449, 1419, 1287, 1220, 1103, 1053, 937, 771, 743 cm–1. Optical Rotation:[α]24 D = 15.53 (c 0.5, CHCl3) M.p.: 165–167 °C. Note: Some of the1H and13C NMR spectral signals of compound 10 were not evident. The O-acetate–protected product was characterized to confirm its structure.A 10-mL vial equipped with a magnetic stirrer bar was charged with 10 (30 mg, 0.13 mmol), pyridine (1 mL), and acetic anhydride (0.3 mL). The mixture was stirred at room temperature for 12 h. The reaction mixture was diluted with EtOAc (10 mL) and washed with aqueous 1 M HCl (2 × 5 mL), sat. aqueous NaHCO3(5 mL), and brine (5 mL). The organic layer was dried (Na2SO4) and concentrated. The residue was purified through silica gel column chromatography to afford 10-Ac (Rf= 0.47; EtOAc / Et3N, 50:1) as a pale-yellow oil (27.3 mg, 78% yield). 1H NMR (400 MHz, CD3OD) δ 8.26 (dd, J = 4.7, 1.2 Hz, 1H), 7.97 (dt, J = 8.3, 0.9 Hz, 1H), 7.65 (d, J = 3.4 Hz, 1H), 7.16 (dd, J = 8.4, 4.7 Hz, 1H), 6.64–6.52 (m, 1H), 5.12 (td, J = 11.0, 4.6 Hz, 1H), 4.41 (ddd, J = 12.1, 10.4, 4.6 Hz, 1H), 2.19–1.99 (m, 3H), 1.85 (dh, J = 12.5, 3.5, 3.1 Hz, 1H), 1.76 (dddt, J = 15.1, 9.8, 6.5, 3.1 Hz, 1H), 1.45 (s, 3H), 1.39–1.21 (m, 2H), 1.01 (d, J = 6.5 Hz, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (100 MHz, CD3OD) δ 169.80, 145.52, 141.60, 130.29, 128.75, 118.19, 115.86, 101.29, 74.63, 58.10, 39.35, 33.05, 30.68, 30.29, 20.61, 19.08. HRMS (ESI-TOF): [M+H]+calcd for [C16H21N2O2]+m / z 273.1598, found 273.1600. IR (neat, ATR): νmax2952, 2929, 2669, 2854, 1738, 1507, 1417, 1373, 1287, 1243, 1234, 1046, 1030, 775 cm–1. Optical Rotation: [α]25 D = 55.17 (c 0.2, CH2Cl2)Prepared following General procedure A using methyl 1H-indazole (23.6 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10-phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (92.6 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (3 mL) was used to make Solution B. The crude product was purified through FCC to give 11 (Rf= 0.45; hexanes / EtOAc, 3:1) as a white solid (34.5 mg, 75% yield). 1H NMR (400 MHz, CDCl3) δ 8.03 (s, 1H), 7.73 (dt, J = 8.1, 1.0 Hz, 1H), 7.48 (dd, J = 8.6, 0.8 Hz, 1H), 7.41–7.34 (m, 1H), 7.15 (ddd, J = 7.9, 6.8, 0.9 Hz, 1H), 4.36 (ddd, J = 11.2, 9.5, 4.4 Hz, 1H), 4.22 (ddd, J = 11.9, 9.5, 4.4 Hz, 1H), 2.23–2.13 (m, 1H), 2.10–2.02 (m, 2H), 1.96 (tdd, J = 13.3, 12.0, 3.7 Hz, 1H), 1.83 (dp, J = 12.9, 3.5 Hz, 1H), 1.78–1.66 (m, 1H), 1.34– 1.24 (m, 1H), 1.24–1.13 (m, 1H), 1.04 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 140.18, 133.39, 126.35, 123.93, 121.13, 120.80, 109.31, 71.75, 64.30, 41.91, 33.63, 31.07, 30.57, 21.94. HRMS (ESI-TOF): [M+H]+calcd for [C14H19N2O]+m / z 231.1492, found 231.1494. IR (neat, ATR): νmax3369 (br), 3055, 2948, 2922, 2856, 1615, 1498, 1453, 1423, 1320, 1183, 1088, 1051, 1007, 942, 832, 742 cm–1. Optical Rotation:[α]= –35.13 (c 0.25, CHCl3) M.p.: 160–163 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Prepared following General procedure A using methyl 3-chloro-1H-indazole (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 12 (Rf = 0.39; hexanes / EtOAc, 4:1) as a white solid (48.9 mg, 92% yield). 1H NMR (500 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.47–7.37 (m, 2H), 7.19 (t, J = 7.3 Hz, 1H), 4.27 (td, 10.5, 4.5 Hz, 1H), 4.19–4.11 (m, 1H), 2.18–2.10 (m, 1H), 2.04 (brs, 1H), 1.99 (q, J = 6.4 Hz, 2H), 1.82 (dt, J = 13.6, 3.2 Hz, 1H), 1.73–1.65 (m, 1H), 1.25 (q, J = 12.1 Hz, 1H), 1.21–1.09 (m, 1H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 141.64, 133.27, 127.49, 121.41, 120.96, 119.75, 109.64, 71.68, 64.59, 42.03, 33.55, 30.96, 30.53, 21.89. HRMS (ESI-TOF): [M+H]+calcd for [C14H18ClN2O]+m / z 265.1102, found 265.1105. IR (neat, ATR): νmax3326 (br), 3061, 2952, 2944, 2926, 2917, 2862, 1617, 1494, 1467, 1455, 1339, 1196, 1009, 745 cm–1. Optical Rotation:[α]= –24.50 (c 1.0, CHCl3) M.p.: 155–156 °C.Prepared following General procedure A using methyl 4-(oxiran-2-ylmethoxy)-9H- carbazole (47.9 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (92.6 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (3 mL) was used to make Solution B. The crude product was purified through FCC to give 13 (Rf= 0.50; hexanes / EtOAc, 2:1) as a white solid (45.0 mg, 64% yield). 1H NMR (400 MHz, CDCl3) δ 8.42 (dd, J = 14.7, 7.5 Hz, 1H), 7.56 (d, J = 8.0 Hz, 0.5×1H, one of the rotamer), 7.51–7.42 (m, 1H), 7.41–7.33 (m, 2H), 7.33–7.23 (m, 1.5 H, overlap with one of the rotamer), 7.21 (d, J = 8.3 Hz, 0.5×1H), 7.14 (d, J = 8.4 Hz, 0.5×1H), 6.66 (d, J = 7.9 Hz, 1H), 4.57–4.40 (m, 2H), 4.40–4.19 (m, 2H), 3.56–3.51 (m, 1H), 2.98 (t, JAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO = 4.8 Hz, 1H), 2.87 (dd, J = 4.9, 2.7 Hz, 1H), 2.56–2.35 (m, 1H), 2.24–2.10 (m, 1H), 1.98–1.83 (m, 3H), 1.81–1.74 (m, 1H), 1.33–1.18 (m, 2H), 1.07 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 155.34, 155.02, 143.39, 141.10, 139.99, 137.80, 128.36, 126.47, 125.99, 125.13, 124.52, 123.75, 123.55, 123.28, 122.08, 119.53, 119.40, 113.63, 112.22, 111.00, 108.62, 105.09, 102.70, 101.13, 101.09, 69.61, 69.61, 69.53, 69.52, 68.89, 68.88, 68.85, 62.41, 62.11, 50.37, 44.87, 42.44, 34.24, 31.33, 28.20, 28.16, 22.02. HRMS (ESI-TOF): [M+H]+calcd for [C22H26NO3]+m / z 352.1907, found 352.1912. IR (neat, ATR): νmax 3416 (br), 3056, 3007, 2951, 2926, 2873, 1623, 1595, 1581, 1502, 1484, 1453, 1439, 1337, 1268, 1157, 1111, 1052, 783, 751, 718 cm–1. Optical Rotation: [α]24 D = 17.50 (c 1.0, CHCl3) M.p.: 78–81 °C.Prepared following General procedure A using 3-(trifluoromethyl)-1H-pyrazole (27.2 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 14 (Rf = 0.22; hexanes / EtOAc, 4:1) as a white solid (42.1 mg, 85% yield). 1H NMR (500 MHz, CDCl3) δ 7.49 (s, 1H), 6.52 (d, J = 2.3 Hz, 1H), 3.97 (td, J = 10.5, 4.4 Hz, 1H), 3.89 (ddd, J = 13.6, 9.6, 4.2 Hz, 1H), 2.76 (s, 1H), 2.11–2.07 (m, 2H), 1.89 (qd, J = 13.2, 3.8 Hz, 1H), 1.81 (ddd, J = 13.5, 5.8, 3.0 Hz, 1H), 1.68–1.58 (m, 1H), 1.21–1.03 (m, 2H), 0.99 (d, J = 6.6 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 142.33 (q, J = 37.9 Hz), 130.21, 121.27 (q, J = 266.7 Hz), 103.99 (q, J = 1.9 Hz), 72.09, 67.84, 41.95, 33.11, 30.77, 30.71, 21.68. HRMS (ESI-TOF): [M+H]+calcd for [C11H16F3N2O]+m / z 249.1209, found 249.1211. IR (neat, ATR): νmax 3370 (brs), 2953, 2932, 2871, 2855, 1491, 1390, 1372, 1237, 1167, 1130, 1055, 1009, 967, 770 cm–1. Optical Rotation: [α]26 D = –10.83 (c 0.2, CHCl3) M.p.: 56–57 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using 3-phenyl-1H-pyrazole (28.8 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 15 (Rf = 0.29; hexanes / EtOAc, 4:1) as a white solid (42.0 mg, 82% yield). 1H NMR (400 MHz, CDCl3) δ 7.81–7.79 (m, 2H), 7.49 (d, J = 2.4 Hz, 1H), 7.44–7.34 (m, 2H), 7.34–7.27 (m, 1H), 6.58 (d, J = 2.4 Hz, 1H), 4.00–3.85 (m, 2H), 2.24–2.17 (m, 1H), 2.16–2.06 (m, 1H), 1.94–1.79 (m, 2H), 1.57–1.70 (m, 1H), 1.26–1.08 (m, 2H), 1.01 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 151.28, 133.22, 129.25, 128.61, 127.74, 125.62, 102.49, 72.89, 66.41, 41.55, 33.23, 30.70, 30.15, 21.80. HRMS (ESI-TOF): [M+H]+calcd for [C16H21N2O]+m / z 257.1648, found 257.1656. IR (neat, ATR): νmax3365 (br), 2948, 2924, 2867, 2854, 1605, 1498, 1455, 1359, 1226, 1099, 1074, 1049, 1024, 1009, 938, 749, 693 cm–1. Optical Rotation: [α]26 D = 7.26 (c 1.0, CHCl3) M.p.: 100–101 °C.Prepared following General procedure A using 1,5,6,7-tetrahydro-4H-indol-4-one (27.0 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 16 (Rf= 0.32; EtOAc) as a white solid (40.6 mg, 82% yield). 1H NMR (400 MHz, CDCl3) δ 6.62 (d, J = 3.2 Hz, 1H), 6.51 (d, J = 3.2 Hz, 1H), 3.75 (td, J = 10.2, 4.5 Hz, 1H), 3.64 (ddd, J = 13.6, 9.6, 4.1 Hz, 1H), 2.84 (dt, J = 16.2, 6.4 Hz, 1H),Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 2.68 (dt, J = 16.3, 6.0 Hz, 2H), 2.43–2.28 (m, 2H), 2.11–2.04 (m, 3H), 1.99–1.89 (m, 1H), 1.85–1.55 (m, 3H), 1.23–1.03 (m, 2H), 0.99 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 194.59, 144.90, 120.26, 118.27, 106.39, 72.85, 62.18, 42.50, 37.68, 33.61, 31.42, 31.15, 23.57, 22.12, 21.79. HRMS (ESI-TOF): [M+H]+calcd for [C15H22NO2]+m / z 248.1645, found 248.1648. IR (neat, ATR): νmax 3369 (br), 2948, 2928, 2866, 1631, 1501, 1471, 1417, 1384, 1255, 1228, 1190, 1111, 1054, 936, 753, 705 cm–1. Optical Rotation: [α]26 D = –4.93 (c 1.0, CHCl3) M.p.: 160–163 °C.Prepared following General procedure A using 4-chloro-5-iodo-7H-pyrrolo[2,3- d]pyrimidine (55.9 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 17 (Rf = 0.52; DCM / MeOH, 10:1) as a white solid (62.0 mg, 79% yield). 1H NMR (400 MHz, CDCl3) δ 8.52 (s, 1H), 7.45 (s, 1H), 4.49 (ddd, J = 12.1, 10.2, 4.4 Hz, 1H), 3.96 (td, J = 10.7, 4.5 Hz, 1H), 2.17–2.10 (m, 1H), 2.05–1.99 (m, 1H), 1.95 (td, J = 12.7, 3.7 Hz, 1H), 1.87–1.81 (m, 1H), 1.75–1.62 (m, 1H), 1.31–1.12 (m, 2H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 152.66, 151.30, 150.47, 132.49, 117.10, 72.50, 61.64, 51.29, 43.32, 33.46, 31.16, 30.97, 21.71. HRMS (ESI-TOF): [M+H]+calcd for [C13H16ClIN3O]+m / z 392.0021, found 392.0020. IR (neat, ATR): νmax 3369 (br), 2948, 2928, 2866, 1631, 1501, 1471, 1417, 1384, 1255, 1228, 1190, 1111, 1054, 936, 753, 705 cm–1. Optical Rotation: [α]26 D = –3.67 (c 0.2, CHCl3) M.p.: 160 °C (decomposition)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using phthalimide (147 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (19.8 mg, 0.200 mmol, 20 mol %), 1,10-phenanthroline (36.0 mg, 0.200 mmol, 20 mol %), and MeCN (10 mL) to make Solution A. (–)-Isopulegol (386 mg, 2.50 mmol, 2.5 equiv) was used for ozonolysis and MeCN (12.5 mL) was used to make Solution B. The crude product was purified through FCC to give 18 (Rf= 0.27; hexanes / EtOAc, 2:1) as a white solid (211.0 mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.78 (dd, J = 5.4, 3.1 Hz, 2H), 7.67 (dd, J = 5.4, 3.1 Hz, 2H), 4.32 (td, J = 10.7, 4.5 Hz, 1H), 3.92 (ddd, J = 12.6, 10.2, 4.0 Hz, 1H), 2.21 (qd, J = 12.4, 3.5 Hz, 1H), 2.14–2.03 (m, 1H), 1.80–1.71 (m, 2H), 1.71–1.60 (m, 1H), 1.15–1.00 (m, 2H), 0.97 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.87, 133.83, 131.97, 123.11, 69.07, 57.32, 43.88, 33.77, 31.12, 28.13, 21.88. HRMS (DART): [M+H]+calcd for [C15H18NO3]+m / z 260.1281, found 260.1281. IR (neat, ATR): νmax3523 (br), 2947, 2928, 2871, 2850, 1763, 1700, 1393, 1379, 1074, 1028, 1008, 887, 717 cm–1. Optical Rotation: [α]26 D = –15.23 (c 1.0, CHCl3) M.p.: 171–174 °C.Prepared following General procedure A using pyrimidin-2-amine (19.0 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10- phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (92.6 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (3 mL) was used to make Solution B. The crude product was purified through FCC to give 19 (Rf = 0.21; DCM / toluene / MeOH, 5:5:1) as a colorless oil (21.1 mg, 51% yield). 1H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 4.4 Hz, 2H), 6.53 (t, J = 4.8 Hz, 1H), 5.44 (d, J = 5.4 Hz, 1H), 3.64 (dtd, J = 13.9, 6.6, 3.3 Hz, 1H), 3.47 (ddd, J = 10.9, 9.6, 4.5 Hz, 1H),Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 2.06–1.98 (m, 2H), 1.68 (dp, J = 12.9, 3.4 Hz, 1H), 1.56–1.43 (m, 1H), 1.32 (qd, J = 13.0, 3.8 Hz, 1H), 1.17–0.98 (m, 2H), 0.94 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 162.73, 157.91, 110.92, 75.88, 57.17, 43.11, 33.38, 31.56, 30.77, 21.82. HRMS (ESI-TOF): [M+H]+calcd for [C11H18N3O]+m / z 208.1444, found 208.1451. IR (neat, ATR): νmax 3274 (br), 2948, 2925, 2853, 1589, 1530, 1452, 1417, 1361, 1240, 1051, 800, 776 cm–1. Optical Rotation: [α]= 13.77 (c 1.0, CHCl3)Prepared following General procedure A using 2-amino-4-chlorobenzonitrile (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10- phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. (–)- Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 20 (Rf = 0.24; toluene / EtOAc, 15:1) as a pale-yellow solid (81.5 mg, 77% yield). 1H NMR (400 MHz, CDCl3) δ 7.27 (d, J = 8.3 Hz, 1H), 6.82 (d, J = 1.8 Hz, 1H), 6.63 (dd, J = 8.3, 1.8 Hz, 1H), 3.51 (ddd, J = 11.0, 9.3, 4.4 Hz, 1H), 3.18 (ddd, J = 11.6, 9.3, 4.2 Hz, 1H), 2.04 (dq, J = 13.0, 3.2 Hz, 2H), 1.72 (dp, J = 12.8, 3.3 Hz, 1H), 1.63–1.50 (m, 1H), 1.31– 1.00 (m, 3H), 0.97 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 151.19, 140.87, 133.73, 117.41, 117.28, 111.84, 94.80, 73.98, 59.21, 42.28, 33.24, 31.07, 31.00, 21.81. HRMS (ESI-TOF): [M+H]+calcd for [C14H18ClN2O]+m / z 265.1102, found 265.1108. IR (neat, ATR): νmax3386 (br), 2948, 2926, 2868, 2215, 1601, 1571, 1507, 1434, 1282, 1105, 1048, 912 cm–1. Optical Rotation: [α]24 D = –2.10 (c 1.0, CHCl3) M.p.: 114–117 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using 3-fluoro-4-(trifluoromethyl)aniline (71.6 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10- phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. (–)- Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 21 (Rf = 0.16; toluene / EtOAc, 15:1) as a white solid (62.9 mg, 54% yield). 1H NMR (400 MHz, CDCl3) δ 7.30 (t, J = 8.3 Hz, 1H), 6.44 (s, 1H), 6.41 (s, 1H), 3.43 (ddd, J = 10.9, 9.5, 4.4 Hz, 1H), 3.15–3.05 (m, 1H), 2.11–2.00 (m, 2H), 1.71 (dp, J = 12.6, 3.3, 2.9 Hz, 1H), 1.61–1.49 (m, 1H), 1.21–1.01 (m, 3H), 0.97 (d, J = 6.6 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 161.21 (dq, J = 252.4, 2.0 Hz), 152.65 (d, J = 11.2 Hz), 127.92 (p, J = 4.3 Hz), 123.33 (qd, J = 268.33, 0.75 Hz), 108.65 (d, J = 2.3 Hz), 106.68 (qd, J = 33.3, 13.0 Hz), 100.50 (d, J = 24.5 Hz).74.21, 59.47, 42.19, 33.25, 31.10, 30.93, 21.79. HRMS (ESI-TOF): [M+H]+calcd for [C14H18F4NO]+m / z 292.1319, found 292.1317. IR (neat, ATR): νmax3385, 2952, 2928, 2871, 2858, 1632, 1587, 1534, 1352, 1323, 1194, 1158, 1121, 1045 cm–1. Optical Rotation: [α]26 D = –17.17 (c 0.2, CHCl3) M.p.: 113–115 °C.Prepared following General procedure A using 5-bromopyridin-2-amine (69.2 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10- phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. (–)-Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 22 (Rf= 0.35; toluene / EtOAc, 3:1) as a white solid (75.1 mg, 66% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 2.4 Hz, 1H), 7.44 (dd, J = 8.8, 2.5 Hz, 1H), 6.38 (d, J = 8.9 Hz, 1H), 4.42 (d, J = 5.6 Hz, 1H), 3.53–3.35 (m, 2H), 2.04 (dq, J = 12.7, 3.6 Hz, 1H), 1.98 (dq, J = 12.7, 3.6 Hz, 1H), 1.69 (dp, J = 12.8, 3.3 Hz, 1H), 1.57–1.42 (m, 1H), 1.35–1.22 (m, 1H), 1.18–0.98 (m, 2H), 0.95 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 157.56, 147.72, 140.01, 110.23, 107.31, 75.91, 57.95, 42.96, 33.45, 31.72, 30.80, 21.81. HRMS (ESI-TOF): [M+H]+calcd for [C12H18BrN2O]+m / z 285.0597, found 285.0595. IR (neat, ATR): νmax 3329, 2951, 2924, 2868, 2832, 1596, 1505, 1581, 1456, 1390, 1377, 1049 cm–1. Optical Rotation: [α]25 D = 22.00 (c 0.1, CHCl3). M.p.: 66–69 °C.Prepared following General procedure A using 2-iodobenzamide (49.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10-phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (3 mL) to make Solution A. (–)-Isopulegol (92.6 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (3 mL) was used to make Solution B. The crude product was purified through FCC to give 23 (Rf= 0.38; toluene / EtOAc, 1:1) as a white solid (51.6 mg, 72% yield). 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 8.0, 1.1 Hz, 1H), 7.47–7.33 (m, 2H), 7.10 (td, J = 7.6, 1.9 Hz, 1H), 5.80 (d, J = 6.2 Hz, 1H), 3.82 (dddd, J = 11.9, 9.8, 7.7, 4.4 Hz, 1H), 3.48 (td, J = 10.6, 4.4 Hz, 1H), 2.46 (brs, 2H), 2.13 (dq, J = 12.6, 3.5 Hz, 1H), 2.06 (ddd, J = 12.8, 6.0, 4.3 Hz, 1H), 1.77–1.66 (m, 1H), 1.56–1.44 (m, 1H), 1.33 (qd, J = 12.9, 3.7 Hz, 1H), 1.20–1.02 (m, 2H), 0.97 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.85, 141.95, 139.81, 131.30, 128.49, 128.28, 92.45, 74.68, 56.44, 42.92, 33.12, 30.89, 30.85, 21.75. HRMS (ESI-TOF): [M+H]+calcd for [C14H19INO2]+m / z 360.0455, found 360.04561. IR (neat, ATR): νmax3250, 2945, 2921, 2865, 2847, 1633, 1541, 1452, 1336, 1060, 1050, 1015, 851, 769, 732, 686 cm–1. Optical Rotation: [α]24 D = –28.27 (c 1.0, CHCl3).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO M.p.: 215–218 °C.Prepared following General procedure A using 3-bromobenzenesulfonamide (47.2 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10- phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (61.7 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 24 (Rf= 0.24; hexanes / EtOAc, 2:1) as a pale-yellow oil (44.6 mg, 64% yield). 1H NMR (400 MHz, CDCl3) δ 8.06 (t, J = 1.8 Hz, 1H), 7.84 (ddd, J = 7.9, 1.8, 1.0 Hz, 1H), 7.70 (ddd, J = 8.0, 1.8, 0.9 Hz, 1H), 7.40 (t, J = 7.9 Hz, 1H), 5.29 (d, J = 6.7 Hz, 1H), 3.36 (ddd, J = 11.1, 9.6, 4.4 Hz, 1H), 2.92–2.84 (m, 1H), 1.97 (ddd, J = 12.6, 6.5, 4.1 Hz, 1H), 1.75 (dq, J = 13.0, 3.5 Hz, 1H), 1.56 (dp, J = 12.8, 3.2 Hz, 1H), 1.51–1.38 (m, 1H), 1.19 (qd, J = 13.8, 4.3 Hz, 1H), 1.05–0.94 (m, 1H), 0.93–0.79 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 142.53, 135.77, 130.69, 130.01, 125.63, 123.04, 72.81, 59.85, 42.13, 33.10, 31.41, 30.76, 21.66. HRMS (ESI-TOF): [M+Na]+calcd for [C13H18BrNNaO3S]+m / z 370.0083, found 370.0081. IR (neat, ATR): νmax3496 (br), 3274 (br), 2949, 2926, 2868, 1571, 1459, 1407, 1328, 1295, 1160, 1100, 1070, 1052, 904, 786, 768, 679, 658, 605, 576 cm–1. Optical Rotation: [α]29 D = –4.83 (c 1.0, CHCl3).Prepared following General procedure A using (S)-1-tosylpyrrolidine-2-carboxamide (107 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10- phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. (–)- Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 25 (Rf= 0.43; DCM / MeOH, 20:1) as a white solid (118.2 mg, 78% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.77–7.65 (m, 2H), 7.34 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 7.0 Hz, 1H), 4.02 (dd, J = 8.8, 3.1 Hz, 1H), 3.65–3.52 (m, 2H), 3.46–3.35 (m, 1H), 3.16 (td, J = 9.8, 6.5 Hz, 1H), 2.44 (s, 3H), 2.16 (ddt, J = 12.1, 6.3, 2.9 Hz, 1H), 2.08–1.92 (m, 2H), 1.83–1.65 (m, 2H), 1.64–1.53 (m, 2H), 1.49 (dddd, J = 11.9, 8.5, 6.5, 3.3 Hz, 1H), 1.39 (qd, J = 13.1, 3.8 Hz, 1H), 1.13–0.96 (m, 2H), 0.94 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 173.19, 144.55, 132.54, 130.04, 127.90, 74.84, 62.68, 56.14, 50.09, 43.13, 33.15, 30.86, 30.56, 30.44, 24.30, 21.76, 21.60. HRMS (DART): [M+H]+calcd for [C19H29N2O4S]+m / z 381.1843 found 381.1842. IR (neat, ATR): νmax 3519 (br), 3393 (br), 2950, 2926, 2869, 1651, 1531, 1344, 1159, 1093, 1052, 754, 664 cm–1. Optical Rotation: [α]24 D = –55.00 (c 0.34, CHCl3). M.p.: 169–172 °C.Prepared following General procedure A using (S)-2-(4-isobutylphenyl)propanamide (82.1 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10- phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. (–)- Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 26 (Rf = 0.29; Et2O) as a white solid (39.9 mg) and also as an impure material. The fractions containing the impure material were concentrated and subjected again to FCC to give another 43.9 mg of 26. Combined, 83.8 mg of 26 was obtained, giving an isolated yield of 66%. 1H NMR (400 MHz, CDCl3) δ 7.21–7.13 (m, 2H), 7.13–7.05 (m, 2H), 5.41 (d, J = 7.0 Hz, 1H), 3.63 (brs, 1H)3.61–3.39 (m, 2H), 3.34–3.19 (m, 1H), 2.44 (d, J = 7.2 Hz, 2H), 2.06– 1.93 (m, 1H), 1.84 (dp, J = 13.6, 6.8 Hz, 1H), 1.74 (ddd, J = 11.7, 7.2, 3.0 Hz, 1H), 1.58 (dp, J = 12.5, 2.9 Hz, 1H), 1.49 (d, J = 7.2 Hz, 3H), 1.38 (dddq, J = 15.0, 9.7, 6.4, 3.2 Hz, 1H), 1.11– 0.99 (m, 2H), 0.99–0.92 (m, 1H), 0.92–0.85 (m, 9H). 13C NMR (100 MHz, CDCl3) δ 176.64, 140.80, 138.38, 129.67, 127.26, 75.04, 55.83, 46.62, 45.01, 43.07, 33.04, 30.75, 30.69, 30.16, 22.38, 22.37, 21.70, 18.57. HRMS (DART): [M+H]+calcd for [C20H32NO2]+m / z 318.2428, found 318.2428.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax3325, 3298, 2960, 2944, 2932, 2906, 2866, 2846, 1646, 1547, 1459, 1048 cm–1. Optical Rotation: [α]24 D = 11.17 (c 0.1, CHCl3).Prepared following General procedure A using celecoxib (153 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. (–)-Isopulegol (123 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) was used to make Solution B. The crude product was purified through FCC to give 27 (Rf = 0.26; hexanes / EtOAc, 3:2) as a white solid (155.9 mg, 79% yield). 1H NMR (400 MHz, CDCl3) δ 7.94–7.85 (m, 2H), 7.51–7.41 (m, 2H), 7.15 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.2 Hz, 2H), 6.74 (s, 1H), 5.34 (d, J = 6.9 Hz, 1H), 3.33 (td, J = 10.9, 4.4 Hz, 1H), 2.83 (tdd, J = 13.9, 7.9, 3.3 Hz, 2H), 2.36 (s, 3H), 2.01–1.89 (m, 1H), 1.70 (dq, J = 12.8, 3.4 Hz, 1H), 1.60–1.51 (m, 1H), 1.49–1.37 (m, 1H), 1.17 (qd, J = 13.1, 3.7 Hz, 1H), 0.96 (q, J = 12.1 Hz, 1H), 0.88 (d, J = 6.5 Hz, 3H), 0.81 (td, J = 13.3, 12.6, 3.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 145.36, 144.05 (q, J = 38.6 Hz), 142.42, 140.14, 139.80, 129.73, 128.72, 128.16, 125.67, 125.64, 121.06 (q, J = 269.1 Hz), 106.25 (q, J = 2.0 Hz), 72.72, 59.84, 42.13, 33.14, 31.29, 30.75, 21.66, 21.32. HRMS (ESI-TOF): [M+H]+calcd for [C24H27F3N3O3S]+m / z 494.1720, found 494.1720. IR (neat, ATR): νmax3487 (br), 3269 (br), 2950, 2927, 2871, 1598, 1472, 1450, 1374, 1332, 1272, 1237, 1161, 1136, 1096, 976, 843, 760, 633 cm–1. Optical Rotation: [α]25 D = –4.50 (c 0.4, CHCl3). M.p.: 171–181 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using lamivudine (91.7 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10-phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), MeCN (4 mL), and MeOH (4 mL) to make Solution A. (–)-Isopulegol (185 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 28 (Rf = 0.41; DCM / MeOH, 4:1) as a yellow solid (133.8 mg, 98% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 7.5 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 6.16 (t, J = 5.2 Hz, 1H), 5.73 (d, J = 7.5 Hz, 1H), 5.26 (t, J = 5.8 Hz, 1H), 5.12 (t, J = 4.6 Hz, 1H), 4.64 (d, J = 4.5 Hz, 1H), 3.68 (h, J = 7.1 Hz, 2H), 3.62–3.54 (m, 1H), 3.35 (dd, J = 11.6, 5.5 Hz, 1H), 3.27–3.23 (m, 1H), 2.98 (dd, J = 11.6, 5.0 Hz, 1H), 1.92–1.74 (m, 2H), 1.54 (d, J = 12.7 Hz, 1H), 1.44–1.32 (m, 1H), 1.06 (qd, J = 13.0, 3.1 Hz, 1H), 0.99–0.77 (m, 5H). 13C NMR (100 MHz, DMSO-d6) δ 163.91, 155.09, 139.85, 95.54, 87.01, 86.16, 71.81, 63.37, 55.76, 43.95, 36.66, 33.39, 31.13, 30.92, 22.38. HRMS (ESI-TOF): [M+Na]+calcd for [C15H23N3NaO4S]+m / z 364.1301, found 364.1307. IR (neat, ATR): νmax3277 (br), 3134, 2950, 2925, 2862, 1643, 1579, 1502, 1337, 1269, 1051, 755 cm–1. Optical Rotation: [α]25 D = –10.50 (c 0.2, CHCl3). M.p.: 131–134 °C.Prepared following General procedure A using the peptide S29 (113 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10-phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (2 mL) to make Solution A. (–)-Isopulegol (92.6 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (3 mL) was used to make SolutionAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO B. The crude product was purified through FCC to give 29 (Rf= 0.47; EtOAc / hexanes, 2:1) as a pale-yellow solid (113.1 mg, 84% yield). 1H NMR (400 MHz, CDCl3) δ 7.46 (d, J = 7.8 Hz, 1H), 7.40 (d, J = 8.3 Hz, 1H), 7.25– 7.08 (m, 6H), 7.08–7.00 (m, 2H), 6.87–6.10 (m, 2H), 4.64 (q, J = 6.7 Hz, 1H), 4.52 (br, 1H), 3.99 (tt, J = 12.9, 7.8 Hz, 2H), 3.73 (m, 4H), 3.34 (dd, J = 14.8, 5.1 Hz, 1H), 3.29–2.97 (m, 4H), 2.86 (s, 1H), 2.13 (d, J = 12.5 Hz, 1H), 1.96 (dt, J = 11.0, 3.6 Hz, 1H), 1.90–1.76 (m, 3H), 1.76–1.55 (m, 4H), 1.29 (s, 9H), 1.21–1.80 (m, 3H), 1.02 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 172.40, 172.02, 170.46, 155.64, 137.32, 136.62, 129.17, 128.50, 127.73, 126.85, 123.28, 121.56, 119.13, 118.55, 110.04, 109.13, 80.79, 72.44, 61.81, 60.30, 53.40, 52.86, 52.37, 46.93, 42.49, 36.68, 34.00, 31.36, 31.20, 30.29, 28.66, 28.21, 27.55, 27.03, 24.29, 23.20, 21.96. HRMS (DART): [M+H]+calcd for [C38H51N4O7]+m / z 675.3752, found 675.3763. IR (neat, ATR): νmax3310 (br), 2952, 2926, 2853, 1743, 1670, 1522, 1463, 1401, 1366, 1248, 1215, 1163, 1128, 756 cm–1. Optical Rotation: [α]25 D = –20.39 (c 0.2, CHCl3). M.p.: 101–132 °C.Prepared following General procedure A using the peptide S30 (165 mg, 0.200 mmol, 1.0 equiv), tetrakis(acetonitrile)copper(I) tetrafluoroborate (18.9 mg, 0.0600 mmol, 30 mol %), 1,10-phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (5 mL) to make Solution A and (–)-isopulegol (154 mg, 1.00 mmol, 5.0 equiv) and MeCN (5 mL) to make Solution B. The crude product was purified through FCC to give 30 (Rf = 0.46; EtOAc / hexanes, 7:3) as a fine white solid (149.5 mg, 80% yield). 1H NMR (400 MHz, CD3OD) δ 7.63–7.48 (m, 1H), 7.45–7.35 (m, 1H), 7.29–6.93 (m, 12H), 4.69–4.32 (m, 4H), 4.12–3.90 (m, 2H), 3.67–3.47 (m, 4H), 3.27–2.88 (m, 5H), 2.87– 2.55 (m, 2H), 2.16–1.57 (m, 9H), 1.54–1.40 (m, 11H), 1.39–1.11 (m, 11H), 1.01 (d, J = 6.0 Hz, 3H). 13C NMR (125 MHz, CD3OD) δ 173.79, 173.65, 173.33, 173.18, 173.11, 172.89, 157.65, 157.45, 153.39, 151.77, 151.37, 138.77, 138.67, 137.91, 137.86, 135.84, 134.98,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 131.61, 130.34, 130.31, 129.49, 129.48, 129.25, 127.88, 124.75, 124.55, 122.69, 122.34, 122.13, 120.09, 119.89, 119.53, 111.08, 110.97, 110.92, 110.75, 84.28, 84.14, 80.77, 80.65, 73.28, 62.49, 62.33, 61.66, 61.44, 56.77, 55.42, 55.34, 55.24, 55.01, 52.69, 44.48, 44.20, 39.18, 38.75, 38.48, 37.94, 35.01, 34.95, 32.87, 32.66, 32.52, 30.01, 29.04, 28.83, 28.68, 27.91, 25.93, 22.44, 22.38, 22.31. HRMS (DART): [M–Boc+2H]+calcd for [C47H60N5O9]+m / z 838.4386, found 838.4356. IR (neat, ATR): νmax 3347 (br), 2952, 2933, 2861, 1757, 1651, 1512, 1449, 1368, 1273, 1256, 1150cm–1. Optical Rotation: [α]26 D = –10.00 (c 0.2, MeOH). M.p.: 119–130 °C.Prepared following General procedure B using 3-chloro-1H-indazole (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (+)-Nootkatone (87.3 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Suspension B. The crude product was purified through FCC to give 31a (Rf= 0.34; hexanes / EtOAc, 2:1) as a colorless oil (54.4 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 3.5 Hz, 2H), 7.34 (s, 1H), 7.21 (dt, J = 7.9, 3.9 Hz, 1H), 5.85 (d, J = 1.4 Hz, 1H), 4.87–4.69 (m, 1H), 2.76–2.67 (m, 1H), 2.55 (dt, J = 15.5, 3.4 Hz, 1H), 2.32–2.17 (m, 5H), 2.16–2.08 (m, 1H), 2.01 (t, J = 12.8 Hz, 1H), 1.26 (s, 3H), 0.93 (d, J = 6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.05, 167.03, 140.10, 132.92, 128.33, 127.46, 125.56, 121.44, 121.15, 120.04, 109.04, 54.15, 43.59, 41.66, 40.25, 39.76, 31.83, 31.81, 16.99, 14.89. HRMS (ESI-TOF): [M+H]+calcd for [C19H22ClN2O]+m / z 329.1415, found 329.1425. IR (neat, ATR): νmax 2966, 2942, 2876, 1664, 1617, 1494, 1465, 1337, 1206, 983, 765, 745 Optical Rotation: [α]25 D = 48.1 (c 1.0, CHCl3).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using phthalimide (368 mg, 2.50 mmol, 1.0 equiv), copper(I) chloride (49.5 mg, 0.500 mmol, 20 mol %), 1,10-phenanthroline (90.1 mg, 0.500 mmol, 20 mol %), and MeCN (25 mL) to make Solution A. (+)-Nootkatone (1.09 g, 5.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (50 mL) was used to make Solution B. The crude product was purified through FCC to give 31b (Rf = 0.34; toluene / Et2O, 3:1) as a yellow oil (638 mg, 79% yield). 1H NMR (600 MHz, CDCl3) δ 7.94–7.76 (m, 2H), 7.76–7.60 (m, 2H), 5.83 (s, 1H), 4.58 (tt, J = 12.6, 3.4 Hz, 1H), 3.57–3.41 (m, 1H), 2.63 (td, J = 14.7, 4.4 Hz, 1H), 2.55–2.40 (m, 2H), 2.32–2.18 (m, 3H), 2.18–2.09 (m, 1H), 1.98–1.86 (m, 2H), 1.24–1.15 (m, 4H), 0.94 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.11, 168.23, 167.49, 134.04, 131.84, 125.41, 123.19, 46.66, 41.67, 40.84, 40.25, 39.83, 32.19, 29.16, 16.67, 14.84. HRMS (DART): [M+H]+calcd for [C20H22NO3]+m / z 324.1594, found 324.1588. IR (neat, ATR): νmax2965, 2940, 2881, 1768, 1708, 1664, 1615, 1375, 1288, 1081, 979, 722 cm–1. Optical Rotation: [α]25 D = 46.50 (c 0.2, CH2Cl2).Prepared following General procedure A using 3-chloro-1H-indazole (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S32 (94.5 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 32a (Rf= 0.28; hexanes / EtOAc, 2:1) as a white solid (50.8 mg, 73% yield). 1H NMR (400 MHz, CDCl3) δ 7.64 (dt, J = 8.2, 1.0 Hz, 1H), 7.45–7.31 (m, 2H), 7.17 (ddd, J = 8.0, 6.1, 1.6 Hz, 1H), 4.79 (dddd, J = 12.1, 10.6, 6.1, 4.5 Hz, 1H), 2.81 (q, J = 6.6 Hz,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H), 2.67–2.51 (m, 1H), 2.46–2.32 (m, 2H), 2.27 (td, J = 12.9, 3.9 Hz, 1H), 2.11 (td, J = 14.0, 4.0 Hz, 1H), 1.92–1.80 (m, 3H), 1.50–1.59 (m, 2H), 1.30 (s, 3H), 1.00 (d, J = 6.7 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 209.31, 140.15, 132.66, 127.19, 121.21, 120.93, 119.81, 109.21, 78.72, 54.07, 51.94, 37.50, 34.58, 34.52, 31.32, 26.89, 21.32, 6.57. HRMS (ESI-TOF): [M+H]+calcd for [C19H24ClN2O2]+m / z 347.1521, found 347.1532. IR (neat, ATR): νmax 3432(br), 2990, 2976, 2958, 2949, 2929, 2912, 1709, 1619, 1496, 1462, 1338, 1202, 1190, 1146, 1054, 988, 772, 766, 743 cm–1. Optical Rotation: [α]25 D = 15.70 (c 1.0, CHCl3). M.p.: 207 °C (decomposition)Prepared following General procedure A using phthalimide (147 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (19.8 mg, 0.200 mmol, 20 mol %), 1,10-phenanthroline (36.0 mg, 0.200 mmol, 20 mol %), and MeCN (10 mL) to make Solution A. The alkene S32 (473 mg, 2.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (10 mL) was used to make Solution B. The crude product was purified through FCC to give 32b (Rf = 0.27; hexanes / EtOAc, 2:1) as a white solid (290.2 mg, 85% yield). 1H NMR (400 MHz, CDCl3) δ 7.82–7.73 (m, 2H), 7.73–7.63 (m, 2H), 4.53 (tt, J = 12.7, 4.6 Hz, 1H), 2.83 (q, J = 6.6 Hz, 1H), 2.65–2.32 (m, 4H), 2.19–1.98 (m, 2H), 1.91 (s, 1H), 1.63–1.41 (m, 4H), 1.26 (s, 3H), 1.00 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 209.80, 168.32, 133.91, 131.92, 123.10, 78.37, 51.87, 46.36, 37.51, 37.31, 34.49, 31.88, 31.23, 23.68, 21.22, 6.56. HRMS (DART): [M+H]+calcd for [C20H24NO4]+m / z 342.1700, found 342.1708. IR (neat, ATR): νmax3531 (brs), 2934, 2926, 2878, 2857, 1769, 1705, 1467, 1397, 1376, 1096, 991, 882, cm–1. Optical Rotation: [α]24 D = 14.50 (c 0.1, CHCl3). M.p.: 232–234 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using 3-chloro-1H-indazole (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (11.9 mg, 0.120 mmol, 30 mol %), 1,10-phenanthroline (21.6 mg, 0.120 mmol, 30 mol %), and MeCN (4 mL) to make Solution A. The alkene S33 (300 mg, 1.20 mmol, 3 equiv) was used for ozonolysis and MeCN (6 mL) was used to make Solution B. The crude product was purified through FCC to give 33-major (Rf = 0.55; hexanes / Et2O, 1:4) as a white solid (58.2 mg, 40% yield) and 33-minor (Rf= 0.50; hexanes / Et2O, 1:4) as a colorless oil (11.6 mg, 8.0% yield). Note: 35-minor arose from impure S33. The alkene S33 could not be prepared in pure form.1H NMR (400 MHz, CDCl3) δ 7.63 (d, J = 8.2 Hz, 1H), 7.40 (ddd, J = 8.0, 6.9, 0.9 Hz, 1H), 7.31 (d, J = 8.5 Hz, 1H), 7.23–7.14 (m, 1H), 4.89 (ddd, J = 10.6, 6.5, 2.2 Hz, 1H), 3.73 (s, 3H), 2.86 (qd, J = 7.3, 2.0 Hz, 1H), 2.81–2.73 (m, 2H), 2.54 (dt, J = 3.5, 2.3 Hz, 1H), 2.33– 2.17 (m, 2H), 1.96 (ddd, J = 14.2, 10.7, 2.2 Hz, 1H), 1.33 (d, J = 7.4 Hz, 3H), 1.06 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 213.50, 174.76, 140.39, 133.20, 127.45, 121.77, 121.54, 120.15, 108.77, 56.28, 51.88, 48.20, 46.63, 45.67, 38.38, 34.88, 26.35, 22.10, 9.52. HRMS (DART): [M+H]+calcd for [C19H22ClN2O3]+m / z 361.1313, found 361.1314. IR (neat, ATR): νmax 2947, 2879, 1616, 1466, 1365, 1337, 1169, 1061,1033, 765, 747 cm–1. Optical Rotation: [α]24 D = –1.00 (c 0.2, CHCl3). M.p.: 142–144 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO1H NMR (400 MHz, CDCl3) δ 7.65 (dt, J = 8.2, 0.9 Hz, 1H), 7.42 (ddd, J = 8.4, 6.8, 1.1 Hz, 1H), 7.34 (d, J = 8.6 Hz, 1H), 7.20 (ddd, J = 7.8, 6.8, 0.9 Hz, 1H), 4.93 (ddd, J = 10.9, 4.8, 2.7 Hz, 1H), 3.73 (s, 3H), 2.74 (q, J = 7.5 Hz, 1H), 2.65 (q, J = 2.9 Hz, 1H), 2.63–2.59 (m, 1H), 2.55 (ddd, J = 14.4, 6.7, 2.9 Hz, 1H), 2.48 (dd, J = 14.3, 4.9 Hz, 1H), 2.31 (dd, J = 14.2, 10.9 Hz, 1H), 2.20 (ddd, J = 14.0, 10.3, 3.3 Hz, 1H), 1.27 (s, 3H), 1.15 (d, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 212.78, 174.31, 140.50, 133.44, 127.57, 121.62, 121.57, 120.16, 108.75, 54.84, 51.98, 51.48, 47.91, 44.53, 43.82, 39.80, 26.93, 23.01, 10.41. HRMS (DART): [M+H]+calcd for [C19H22ClN2O3]+m / z 361.1313, found 361.1313. IR (neat, ATR): νmax 2950, 1731, 1616, 1494, 1465, 1339, 1203, 1176, 1021, 761, 748 cm–1. Optical Rotation: [α]25 D = 1.00 (c 0.1, CHCl3).Prepared following General procedure A using 3-chloro-1H-indazole (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S34 (68.1 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) was used to make Solution B. The crude product was purified through FCC to give 34a-major (Rf= 0.68; EtOAc) with impurity and 34a-minor (Rf = 0.29; EtOAc) as a white solid (14.4 mg, 26% yield). The impure material of 34a-major was purified again through FCC to give pure 34a-major (Rf = 0.51; DCM / MeOH, 50:3) as a white solid (26.0 mg, 46% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.69–7.61 (m, 1H), 7.47 (d, J = 8.6 Hz, 1H), 7.42–7.35 (m, 1H), 7.21–7.14 (m, 1H), 4.84 (tt, J = 11.4, 4.1 Hz, 1H), 3.92 (s, 1H), 2.74 (ddd, J = 14.1, 11.6, 2.8 Hz, 1H), 2.37 (qd, J = 12.9, 4.1 Hz, 1H), 2.11 (brs, 1H), 2.08–1.94 (m, 4H), 1.91– 1.80 (m, 1H), 1.74 (ddd, J = 11.2, 3.8, 1.9 Hz, 1H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 140.21, 132.36, 127.18, 121.20, 120.99, 119.79, 109.58, 77.35, 77.03, 76.72, 74.11, 70.76, 52.62, 34.80, 32.80, 27.22, 26.37. HRMS (DART): [M+H]+calcd for [C14H18ClN2O2]+m / z 281.1051, found 281.1051. IR (neat, ATR): νmax 3401 (br), 2965, 2932, 1618, 1496, 1466, 1340, 1198, 1046, 1033, 871, 766, 743 cm–1. Optical Rotation: [α]24 D = –4.33 (c 0.1, CHCl3). M.p.: 158–160 °C.1H NMR (400 MHz, CDCl3) δ 7.67 (d, J = 8.2 Hz, 1H), 7.49–7.34 (m, 2H), 7.20 (ddd, J = 7.8, 6.4, 1.2 Hz, 1H), 4.56 (tt, J = 10.2, 4.7 Hz, 1H), 3.73 (dd, J = 10.6, 4.6 Hz, 1H), 2.41 (brs, 2H), 2.29 (dt, J = 12.8, 3.8 Hz, 1H), 2.25–2.15 (m, 1H), 2.15–1.97 (m, 2H), 1.92 (dt, J = 13.5, 4.2 Hz, 1H), 1.61 (td, J = 13.0, 4.4 Hz, 1H), 1.38 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 140.05, 132.65, 127.51, 121.42, 121.07, 119.98, 109.19, 75.01, 73.27, 55.58, 35.83, 35.29, 28.88, 20.35. HRMS (ESI-TOF): [M+H]+calcd for [C14H18ClN2O2]+m / z 281.1051, found 281.1051. IR (neat, ATR): νmax3393 (br), 2978, 2943, 2871, 1618, 1494, 1465, 1338, 1196, 1143, 1130, 1093, 1071, 994, 767, 743 cm–1. Optical Rotation: [α]24 D = –3.00 (c 0.1, CHCl3). M.p.: 164–166 °C.Prepared following General procedure A using phthalimide (147 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (19.8 mg, 0.200 mmol, 20 mol %), 1,10-phenanthroline (36.0 mg,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 0.200 mmol, 20 mol %), and MeCN (10 mL) to make Solution A. The alkene S34 (681 mg, 4.00 mmol, 4.0 equiv) was used for ozonolysis and MeCN (10 mL) was used to make Solution B. The crude product was purified through FCC (1% MeOH / DCM) to remove most of the impurity. The mixture was purified again through FCC to afford 34b-major (Rf= 0.56; EtOAc / hexanes, 1:1) as a white solid (136.0 mg, 53% yield) and 34b-minor (Rf = 0.23; EtOAc / hexanes, 1:1) as a white solid (61.8 mg, 23% yield).1H NMR (500 MHz, CDCl3) δ 7.85–7.78 (m, 2H), 7.73–7.66 (m, 2H), 4.56 (tt, J = 12.6, 4.1 Hz, 1H), 3.77 (s, 1H), 2.95 (td, J = 13.3, 2.7 Hz, 1H), 2.61–2.45 (m, 1H), 1.96 (td, J = 13.8, 4.0 Hz, 1H), 1.74–1.65 (m, 2H), 1.65–1.55 (m, 3H), 1.32 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.43, 133.83, 132.02, 123.08, 74.16, 70.28, 44.57, 32.73, 32.25, 27.02, 24.46. HRMS (DART): [M+H]+calcd for [C15H18NO4]+m / z 276.1230, found 276.1232. IR (neat, ATR): νmax3441 (br), 2956, 2926, 2852, 1768, 1707, 1398,1377, 1088, 884, 718 Optical Rotation: [α]26 D = –14.00 (c 0.2, MeOH). M.p.: 231–234 °C.1H NMR (500 MHz, CDCl3) δ 7.86–7.78 (m, 2H), 7.76–7.67 (m, 2H), 4.29 (tt, J = 12.6, 4.6 Hz, 1H), 3.62 (dd, J = 12.0, 4.5 Hz, 1H), 2.46–2.28 (m, 2H), 2.17 (s, 1H), 2.20–1.89 (m, 2H), 1.85 (dt, J = 13.2, 3.5 Hz, 1H), 1.66 (dtd, J = 13.4, 4.3, 2.2 Hz, 1H), 1.55 (td, J = 13.6, 4.1 Hz, 1H), 1.37 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.14, 134.02, 131.85, 123.22, 75.74, 73.38, 47.85, 36.63, 33.65, 26.40, 18.83. HRMS (DART): [M+H]+calcd for [C15H18NO4]+m / z 276.1230, found 276.1233.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax3405 (brs), 2925, 2852, 1762, 1709, 1467, 1379, 1113, 1974, 1045, 719 cm–1. Optical Rotation: [α]25 D = –0.94 (c 0.2, CHCl3) M.p.: 232–234 °C.Prepared following General procedure A using 3-chloro-1H-indazole (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S35 (157 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) was used to make Solution B. The crude product was purified through FCC to give 35a-major (Rf= 0.46; hexanes / Et2O, 5:1) as a white solid (69.8 mg, 57% yield) and 35a-minor (Rf = 0.38; hexanes / Et2O, 5:1) as a colorless oil (33.5 mg, 27% yield).1H NMR (400 MHz, CDCl3) δ 7.65 (dt, J = 8.2, 1.0 Hz, 1H), 7.41 (tdd, J = 8.6, 6.8, 1.0 Hz, 2H), 7.22–7.13 (m, 1H), 4.66–4.54 (m, 1H), 4.05–3.91 (m, 4H), 2.22 (t, J = 12.4 Hz, 1H), 2.16–2.08 (m, 1H), 2.08–1.97 (m, 2H), 1.94–1.77 (m, 2H), 1.60–1.46 (m, 1H), 0.94 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 140.07, 132.54, 127.17, 121.18, 120.95, 119.79, 110.17, 109.31, 65.51, 65.09, 56.12, 41.17, 39.00, 31.64, 30.09, 13.55. HRMS (DART): [M+H]+calcd for [C16H20ClN2O2]+m / z 307.1208 found 307.1208. IR (neat, ATR): νmax2975, 2963, 2934, 2884, 1616, 1494, 1466, 1337, 1173, 1161, 1094, 1023, 987, 944, 925, 767, 744 cm–1. Optical Rotation: [α]24 D = –3.00 (c 0.2, CHCl3) M.p.: 107–110 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.49–7.36 (m, 2H), 7.18 (ddd, J = 7.9, 6.5, 1.1 Hz, 1H), 4.64 (tt, J = 12.3, 4.1 Hz, 1H), 4.05–3.88 (m, 4H), 2.46 (t, J = 12.6 Hz, 1H), 2.19 (qd, J = 12.9, 4.0 Hz, 1H), 2.05–1.85 (m, 3H), 1.85–1.75 (m, 1H), 1.71–1.63 (m, 1H), 1.16 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 140.09, 132.52, 127.14, 121.16, 120.96, 119.78, 111.23, 109.33, 64.47, 64.46, 56.15, 35.94, 35.63, 27.84, 25.73, 14.58. HRMS (DART): [M+H]+calcd for [C16H20ClN2O2]+m / z 307.1208 found 307.1208. IR (neat, ATR): νmax2965, 2935, 2878, 1616, 1495, 1466, 1339, 1195, 1171, 1153, 1098, 1032, 1006, 957, 846, 766, 744 cm–1. Optical Rotation: [α]25 D = –6.48 (c 0.1, CHCl3)Prepared following General procedure A using phthalimide (294 mg, 2.00 mmol, 1.0 equiv), copper(I) chloride (39.6 mg, 0.400 mmol, 20 mol %), 1,10-phenanthroline (72.1 mg, 0.400 mmol, 20 mol %), and MeCN (20 mL) to make Solution A. The alkene S35 (785 mg, 4.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (20 mL) to make Solution B. The crude product was purified through FCC to give 35b-major (Rf= 0.24; hexanes / EtOAc, 4:1) as a white solid (531.4 mg, 88% yield, 4.1:1 d.r. determined by NMR). Pure 35b-major was obtained through recrystallization (DCM / hexanes). The mother liquor was concentrated in vacuo. Repeating the recrystallization afforded another fraction of pure 35b-major. This mother liquor was concentrated in vacuo to afford a 1:1 mixture of 35b-major and 35b-minor.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CD3CN) δ 7.82–7.67 (m, 4H), 4.24 (tt, J = 12.7, 3.9 Hz, 1H), 3.99–3.83 (m, 4H), 2.26 (t, J = 12.7 Hz, 1H), 2.21–2.10 (m, 1H), 1.88 (ddd, J = 12.5, 3.9, 2.0 Hz, 1H), 1.83–1.66 (m, 3H), 1.43–1.29 (m, 1H), 0.86 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CD3CN) δ 169.17, 135.02, 133.02, 123.65, 110.72, 66.20, 65.79, 49.27, 39.87, 39.28, 31.18, 29.64, 13.93. HRMS (DART): [M+H]+calcd for [C17H20NO4]+m / z 302.1387 found 302.1384. IR (neat, ATR): νmax2976, 2920, 2881, 1710, 1376, 1236, 1089, 1887 cm–1. Optical Rotation: [α]25 D = –3.00 (c 0.2, CH2Cl2). M.p.: 157–159 °C.1H NMR (500 MHz, CDCl3) δ 7.87–7.76 (m, 0.5×2H),7.74–7.61 (m, 0.5×2H), 4.47– 4.34 (m, 0.5×1H), 4.05–3.86 (m, 0.5×4H), 2.69 (t, J = 12.7 Hz, 0.5×1H), 2.37 (qd, J = 13.0, 4.2 Hz, 0.5×1H), 1.94–1.80 (m, 0.5×2H), 1.63–1.55 (m, 0.5×2H), 1.16 (d, J = 7.2 Hz, 0.5×3H). 13C NMR (125 MHz, CDCl3) δ 168.32, 133.92, 132.07, 123.13, 111.17, 64.47, 64.46, 48.32, 35.67, 32.96, 27.96, 22.77, 14.51. HRMS (DART): [M+H]+calcd for [C17H20NO4]+m / z 302.1387 found 302.1386. IR (neat, ATR): νmax2975, 2940, 2881, 1709, 1372, 1173, 1118, 1030 cm–1. Optical Rotation: [α]27 D = –0.65 (c 0.31, CH2Cl2).Prepared following General procedure A using 3-chloro-1H-indazole (76.3 mg, 0.500 mmol, 1.0 equiv), copper(I) chloride (9.90 mg, 0.100 mmol, 20 mol %), 1,10-phenanthroline (18.0 mg, 0.100 mmol, 20 mol %), and MeCN (5 mL) to make Solution A. The alkene S36 (152 mg, 1.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (5 mL) to make Solution B. The crude product was purified through FCC to give 36a-major (Rf= 0.57; CHCl3) as a white solid (88.1 mg, 67% yield) and 36a-minor (Rf = 0.40; CHCl3) as a white solid (22.0 mg, 17 % yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.44–7.32 (m, 2H), 7.18 (ddd, J = 7.9, 5.6, 2.1 Hz, 1H), 4.63 (dddd, J = 9.8, 8.3, 5.2, 2.8 Hz, 1H), 3.26 (s, 1H), 2.57 (ddd, J = 14.9, 8.6, 2.5 Hz, 1H), 2.46 (dd, J = 14.8, 5.2 Hz, 1H), 2.10–1.91 (m, 2H), 1.91–1.82 (m, 1H), 1.82–1.74 (m, 1H), 1.38 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 140.29, 132.52, 127.27, 121.27, 121.06, 119.78, 109.30, 60.50, 57.41, 51.41, 30.91, 27.76, 26.91, 23.85. HRMS (ESI-TOF): [M+H]+calcd for [C14H16ClN2O]+m / z 263.0946, found 263.0950. IR (neat, ATR): νmax3062, 2978, 2956, 2924, 2861, 1616, 1493, 1465, 1379, 1336, 1210, 1192, 1174, 1128, 1971, 1040, 1033, 1018, 1006, 985, 961, 849, 832, 743 cm–1. Optical Rotation: [α]23 D = –7.33 (c 0.1, CHCl3) M.p.: 75–77 °C.1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.45–7.32 (m, 2H), 7.18 (ddd, J = 8.0, 5.4, 2.3 Hz, 1H), 4.47–4.31 (m, 1H), 3.07 (d, J = 5.1 Hz, 1H), 2.56 (dd, J = 15.3, 11.2 Hz, 1H), 2.37 (dddd, J = 15.2, 6.9, 5.2, 1.7 Hz, 1H), 2.33–2.17 (m, 2H), 2.01–1.89 (m, 1H), 1.74–1.65 (m, 1H), 1.40 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.92, 132.59, 127.21, 121.38, 121.23, 119.97, 109.42, 58.14, 57.21, 54.79, 29.96, 29.94, 25.45, 22.75. HRMS (ESI-TOF): [M+H]+calcd for [C14H16ClN2O]+m / z 263.0946, found 263.0945. IR (neat, ATR): νmax3059, 2978, 2960, 2923, 2862, 1616, 1494, 1466, 1435, 1380, 1337, 1233, 1212, 1194, 1129, 1023, 1006, 985, 839, 769, 744 cm–1. Optical Rotation: [α]24 D = –11.00 (c 0.2, CHCl3) M.p.: 82–84 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using phthalimide (368 mg, 2.50 mmol, 1.0 equiv), copper(I) chloride (49.5 mg, 0.500 mmol, 20 mol %), 1,10-phenanthroline (90.1 mg, 0.500 mmol, 20 mol %), and MeCN (25 mL) to make Solution A. The alkene (+)-S36 (761 mg, 5.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (25 mL) to make Solution B. The crude product was purified through FCC to give (–)-36b-major (Rf = 0.55; EtOAc / hexanes, 1:2) as a white solid (357.2 mg, 55% yield) and (–)-36b-minor (Rf= 0.51; EtOAc / hexanes, 1:2) as a white solid (175.9 mg, 27 % yield).1H NMR (400 MHz, CDCl3) δ 7.88–7.75 (m, 2H), 7.75–7.63 (m, 2H), 4.48–4.29 (m, 1H), 3.17 (s, 1H), 2.67 (ddd, J = 14.5, 9.8, 2.3 Hz, 1H), 2.26–2.18 (m, 1H), 2.18–1.98 (m, 2H), 1.97–1.86 (m, 1H), 1.61–1.48 (m, 1H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.43, 133.91, 131.95, 123.10, 60.77, 57.08, 44.19, 28.23, 28.13, 25.01, 24.01. HRMS (DART): [M+H]+calcd for [C15H16NO3]+m / z 258.1125, found 258.1126. IR (neat, ATR): νmax 2926, 2856, 1772, 1719, 1701, 1400, 1376, 1102, 879 cm–1. Optical Rotation: [α]25 D = –2.00 (c 0.2, CHCl3) M.p.: 146–149 °C.1H NMR (400 MHz, CDCl3) δ 7.89–7.76 (m, 2H), 7.74–7.65 (m, 2H), 4.10 (dddd, J = 12.8, 11.9, 6.6, 3.0 Hz, 1H), 3.05–2.92 (m, 1H), 2.60–2.39 (m, 2H), 2.20–2.04 (m, 2H), 1.87 (ddd, J = 14.8, 12.8, 5.0 Hz, 1H), 1.44–1.36 (m, 1H), 1.35 (s, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (100 MHz, CDCl3) δ 168.08, 133.91, 131.94, 123.14, 58.39, 56.97, 46.40, 30.42, 27.92, 23.43, 22.83. HRMS (DART): [M+H]+calcd for [C15H16NO3]+m / z 258.1125, found 258.1126. IR (neat, ATR): νmax2925, 2857, 1701, 11396, 1377, 1075 cm–1. Optical Rotation: [α]25 D = –15.30 (c 0.2, CHCl3) M.p.: 187–190 °C.Prepared following General procedure A using 3-chloro-1H-indazole (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S37 (123 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 37-major (Rf= 0.32; CHCl3 / MeOH, 100:1) as a pale-yellow oil (44.7 mg, 42%) and 37-minor (Rf = 0.47; CHCl3 / MeOH, 100:1) as a pale-yellow oil (40.1 mg, 38 % yield).1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.42–7.36 (m, 2H), 7.18 (ddd, J = 7.9, 4.8, 2.9 Hz, 1H), 4.43 (tt, J = 11.7, 4.2 Hz, 1H), 3.35 (ddd, J = 11.0, 9.9, 4.2 Hz, 1H), 2.33 (dtd, J = 12.0, 4.0, 1.8 Hz, 1H), 2.17–2.07 (m, 1H), 2.07–1.93 (m, 3H), 1.89 (dq, J = 13.8, 3.6 Hz, 1H), 1.47 (dddq, J = 14.5, 8.9, 6.2, 3.1, 2.4 Hz, 1H), 1.25–1.13 (m, 1H), 1.09 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 139.98, 132.58, 127.27, 121.24, 121.04, 119.88, 109.25, 74.86, 56.73, 40.85, 39.33, 31.63, 31.08, 18.03. HRMS (ESI-TOF): [M+H]+calcd for [C14H18ClN2O]+m / z 265.1102, found 265.1105. IR (neat, ATR): νmax 3380 (br), 2949, 2932, 2871, 1616, 1494, 1465, 1338, 1191, 1128, 1049, 1015, 1006, 987, 767, 743 cm–1. Optical Rotation: [α]25 D = –4.00 (c 0.4, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.46–7.35 (m, 2H), 7.18 (ddd, J = 7.8, 6.5, 1.1 Hz, 1H), 4.86 (tt, J = 9.4, 4.2 Hz, 1H), 4.12–4.01 (m, 1H), 2.44 (ddd, J = 13.1, 9.7, 3.0 Hz, 1H), 2.23–2.10 (m, 1H), 2.02 (ddt, J = 15.3, 11.2, 4.1 Hz, 1H), 1.93 (dt, J = 13.7, 4.4 Hz, 1H), 1.88–1.75 (m, 4H), 1.56 (dq, J = 13.7, 4.4 Hz, 1H), 1.11 (d, J = 7.1 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 140.20, 132.16, 127.08, 121.13, 120.94, 119.73, 109.49, 72.20, 53.65, 35.48, 35.03, 27.59, 26.27, 16.99. HRMS (ESI-TOF): [M+H]+calcd for [C14H18ClN2O]+m / z 265.1102, found 265.1107. IR (neat, ATR): νmax 3381 (br), 2954, 2931, 2873, 1616, 1494, 1465, 1339, 1267, 1244, 1192, 1181, 1130, 10058, 1017, 981, 965, 766, 743 cm–1. Optical Rotation: [α]24 D = 3.50 (c 0.2, CHCl3)Prepared following General procedure A using 3-chloro-1H-indazole (153 mg, 1.00 mmol, 1.0 equiv), copper(I) chloride (19.8 mg, 0.200 mmol, 20 mol %), 1,10-phenanthroline (36.0 mg, 0.200 mmol, 20 mol %), and MeCN (10 mL) to make Solution A. The alkene S37 (337 mg, 2.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (10 mL) to make Solution B. The crude product was purified through FCC to give 38-major (Rf = 0.30; hexanes / EtOAc, 2:3) containing impurities and 38-minor (Rf= 0.15; hexanes / EtOAc, 2:3) containing impurities. The crude 38-major was purified again through FCC to give 38-major (Rf= 0.53; Et2O) as a white solid (148.6 mg, 54% yield). The crude 38-minor was purified again through FCC to give 38-minor (Rf= 0.23; toluene / EtOAc, 3:2) as a white solid (71.8 mg, 26% yield).1H NMR (400 MHz, CDCl3) δ 7.65 (dt, J = 8.2, 0.8 Hz, 1H), 7.45–7.34 (m, 2H), 7.19 (ddd, J = 7.9, 6.0, 1.7 Hz, 1H), 4.67 (dqd, J = 9.5, 5.4, 2.6 Hz, 1H), 3.79–3.63 (m, 2H), 3.54 (t,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO J = 2.0 Hz, 1H), 2.57 (ddd, J = 15.0, 8.5, 2.5 Hz, 1H), 2.50 (dd, J = 15.0, 5.4 Hz, 1H), 2.09– 1.97 (m, 3H), 1.97–1.90 (m, 1H), 1.90–1.82 (m, 1H). 13C NMR (100 MHz, CDCl3) δ 140.28, 132.74, 127.41, 121.38, 121.06, 119.86, 109.22, 64.38, 59.87, 56.89, 51.69, 30.49, 26.65, 23.60. HRMS (ESI-TOF): [M+H]+calcd for [C14H16ClN2O2]+m / z 279.0895, found 279.0897. IR (neat, ATR): νmax 3417 (br), 2929, 2865, 1616, 1494, 1466, 1338, 1197, 1052, 1006, 768, 743 cm–1. Optical Rotation: [α]24 D = 8.00 (c 0.1, CHCl3) M.p.: 130–132 °C.1H NMR [400 MHz, (CD3)2CO] δ 7.66 (d, J = 8.6 Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.52–7.37 (m, 1H), 7.21 (t, J = 7.3 Hz, 1H), 4.68 (dtd, J = 10.5, 8.0, 3.8 Hz, 1H), 3.70–3.50 (m, 2H), 3.20 (d, J = 3.9 Hz, 1H), 2.48–2.31 (m, 2H), 2.23–2.04 (m, 3H), 1.76–1.62 (m, 1H). 13C NMR [100 MHz, (CD3)2CO] δ140.38, 131.60, 127.25, 121.46, 120.72, 119.05, 109.92, 65.00, 64.88, 59.91, 54.57, 53.77, 29.78, 25.24, 24.60. HRMS (DART): [M+H]+calcd for [C14H16ClN2O2]+m / z 279.0895, found 279.0895. IR (neat, ATR): νmax3426 (br), 2926, 2858, 1616, 1495, 1466, 1338, 1194, 1056, 1007, 761, 744 cm–1. Optical Rotation: [α]24 D = 22.77 (c 0.1, CHCl3) M.p.: 115–116 °C.Prepared following General procedure A using 3-chloro-1H-indazole (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S39 (67.3 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 39-major (Rf = 0.21; CHCl3 / Et2O, 3 / 2)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO as a white solid (24.6 mg, 44% yield) and 39-minor (Rf= 0.37; CHCl3 / Et2O, 3 / 2) as a colorless oil (22.6 mg, 41% yield).1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.46–7.35 (m, 2H), 7.20 (ddd, J = 7.8, 6.4, 1.3 Hz, 1H), 4.53–4.37 (m, 1H), 4.15–4.05 (m, 1H), 3.21 (d, J = 5.0 Hz, 1H), 2.51 (dd, J = 15.2, 11.1 Hz, 1H), 2.34 (dddd, J = 15.2, 6.7, 5.1, 1.8 Hz, 1H), 2.23 (td, J = 12.3, 10.7 Hz, 1H), 2.16–2.08 (m, 1H), 1.95 (d, J = 9.6 Hz, 1H), 1.53 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 139.87, 133.00, 127.50, 121.44, 121.39, 120.08, 109.19, 70.97, 60.32, 59.96, 53.40, 34.87, 29.51, 18.87. HRMS (ESI-TOF): [M+H]+calcd for [C14H16ClN2O2]+m / z 279.0895, found 279.0895. IR (neat, ATR): νmax 3412 (br), 2982, 2930, 1616, 1494, 1466, 1337, 1319, 1195, 1129, 1049, 1009, 850, 768, 744 cm–1. Optical Rotation: [α]23 D = –3.56 (c 0.1, CHCl3) M.p.: 145–148 °C.1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.49–7.35 (m, 2H), 7.19 (ddd, J = 7.9, 5.8, 1.8 Hz, 1H), 4.73 (dddd, J = 11.1, 8.6, 5.7, 2.9 Hz, 1H), 4.03 (s, 1H), 3.48 (t, J = 2.1 Hz, 1H), 2.60–2.45 (m, 2H), 2.40–2.28 (brs, 1H), 2.15 (ddd, J = 13.8, 10.9, 5.0 Hz, 1H), 1.98–1.88 (m, 1H), 1.52 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 140.36, 132.95, 127.50, 121.47, 121.10, 119.85, 109.20, 68.21, 63.25, 60.18, 48.54, 36.85, 30.46, 21.07. HRMS (ESI-TOF): [M+H]+calcd for [C14H16ClN2O2]+m / z 279.0895, found 279.0893. IR (neat, ATR): νmax 3417 (br), 2978, 2962, 2926, 1617, 1494, 1466, 1337, 1192, 1060, 1039, 1032, 845, 766, 745 cm–1. Optical Rotation: [α]24 D = 4.00 (c 0.2, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using phthalimide (S18, 58.8 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S40 (207 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) was used to make Solution B. The crude product was purified through FCC to give 40 (Rf = 0.49; toluene / DCM, 1:1) as a pale-yellow oil (72.7 mg, 50% yield). 1H NMR (400 MHz, CDCl3) δ 7.96–7.80 (m, 2H), 7.76 (dd, J = 5.4, 3.0 Hz, 2H), 7.62 (dd, J = 5.5, 3.0 Hz, 2H), 7.45 (tt, J = 7.0, 1.2 Hz, 1H), 7.32 (t, J = 7.7 Hz, 2H), 5.70 (td, J = 10.9, 4.7 Hz, 1H), 4.38 (ddd, J = 12.7, 10.6, 4.3 Hz, 1H), 2.51 (qd, J = 13.9, 13.4, 3.9 Hz, 1H), 2.39–2.27 (m, 1H), 1.91–1.75 (m, 3H), 1.37–1.09 (m, 2H), 1.00 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.28, 165.63, 133.86, 132.80, 130.05, 129.54, 128.26, 123.19, 72.21, 53.48, 39.90, 33.62, 30.67, 27.84, 21.75. HRMS (DART): [M+H]+calcd for [C22H22NO4]+m / z 364.1543, found 364.1541 IR (neat, ATR): νmax 2954, 2931, 2870, 2853, 1174, 1722, 1468, 1453, 1382, 1295, 1272, 1114, 1099, 1070, 714 cm–1. Optical Rotation: [α]24 D = –52.72 (c 0.2, CHCl3)Prepared following General procedure A using melatonin (S6, 46.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S41 (62.1 mg, 0.500 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 41 (Rf= 0.26; EtOAc) as an off-white solid (42.8 mg, 68% yield). 1H NMR (400 MHz, CDCl3) δ 7.25 (d, J = 8.9 Hz, 1H), 7.08–6.99 (m, 2H), 6.87 (dd, J = 8.9, 2.5 Hz, 1H), 5.72 (brs, 1H), 4.11 (tt, J = 11.8, 3.7 Hz, 1H), 3.85 (s, 3H), 3.57 (q, J =Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 6.7 Hz, 2H), 2.93 (t, J = 6.8 Hz, 2H), 2.10 (dd, J = 12.9, 2.1 Hz, 2H), 1.94–1.91 (m, 5H), 1.84– 1.73 (m, 1H), 1.66 (qd, J = 12.5, 3.4 Hz, 2H), 1.48 (qt, J = 13.1, 3.4 Hz, 2H), 1.27 (qt, J = 13.1, 3.7 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 170.11, 153.77, 131.31, 127.93, 122.68, 111.71, 110.87, 110.35, 100.59, 56.01, 55.19, 39.99, 33.63, 25.97, 25.65, 25.39, 23.39. HRMS (ESI-TOF): [M+H]+calcd for [C19H27N2O2]+m / z 315.2067, found 315.2075. IR (neat, ATR): νmax3250, 3075, 3000, 2928, 2849, 1636, 1553, 1484, 1452, 1373, 1301, 1231, 1210, 1180, 1107, 1036, 852, 785, 749 cm–1. M.p.: 112–115 °C.Prepared following General procedure A using S7 (63.7 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S42 (90.1 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 42 (Rf= 0.47; hexanes / EtOAc, 2:1) as a pale-yellow oil (61.4 mg, 61% yield). 1H NMR (400 MHz, CDCl3) δ 7.54 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 8.3 Hz, 1H), 7.24– 7.16 (m, 1H), 7.11 (t, J = 7.3 Hz, 1H), 6.97 (s, 1H), 5.04 (d, J = 8.1 Hz, 1H), 4.64 (q, J = 5.5 Hz, 1H), 4.35–4.29 (m, 3H), 3.68 (s, 3H), 3.31– 3.20 (m, 2H), 2.90 (t, J = 12.6 Hz, 2H), 2.05 (d, 2H), 1.86 (qd, J = 12.5, 3.8 Hz, 2H), 1.50 (s, 9H), 1.43 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 172.75, 155.21, 154.62, 135.72, 128.31, 122.44, 121.71, 119.42, 119.16, 109.52, 109.21, 79.99, 79.81, 54.24, 53.38, 52.23, 32.39, 28.46, 28.39, 28.36, 28.15. HRMS (DART): [M+H]+calcd for [C27H44N3O6]+m / z 502.2912, found 502.2914. IR (neat, ATR): νmax3349 (br), 2967, 2952, 2931, 2862, 1744, 1693, 1463, 1426, 1365, 1245, 1165, 742 cm–1. Optical Rotation:= 10.10 (c 1.0, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S43 (166 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 43 (Rf = 0.60; hexanes / EtOAc, 4:1) as a white solid (105.9 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 8.2, 0.9 Hz, 1H), 7.53 (dt, J = 8.5, 0.7 Hz, 1H), 7.47–7.38 (m, 1H), 7.23–7.13 (m, 1H), 4.61 (ddd, J = 13.6, 10.6, 5.7 Hz, 1H), 4.39 (ddd, J = 13.6, 10.6, 5.6 Hz, 1H), 3.03 (s, 1H), 2.05–1.80 (m, 4H), 1.57–1.46 (m, 1H), 1.35 (s, 3H), 1.25 (td, J = 12.9, 12.2, 6.2 Hz, 1H), 0.91 (s, 3H), 0.88–0.79 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 140.56, 132.24, 127.37, 121.08, 121.02, 119.67, 109.83, 60.34, 59.13, 49.15, 44.71, 31.38, 28.01, 27.69, 27.09, 26.76, 26.68, 21.96. HRMS (ESI-TOF): [M+H]+calcd for [C18H24ClN2O]+m / z 319.1572, found 319.1578. IR (neat, ATR): νmax 2959, 2932, 2870, 1616, 1495, 1468, 1378, 1337, 1246, 1175, 1127, 1007, 985, 896, 743 cm–1. M.p.: 70–71 °C.Prepared following modified General procedure B using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S44 (334 mg, 1.20 mmol, 3 equiv) was dissolved in DCM (10 mL) for ozonolysis. MeCN (6 mL) was used to make Suspension B. The crude product was purified through FCC to give 44 (Rf= 0.44; toluene / DCM, 1:1) as a white solid (105.1 mg, 61% yield). 1H NMR (400 MHz, CDCl3) δ 7.67 (dt, J = 8.2, 1.0 Hz, 1H), 7.42 (ddd, J = 7.8, 6.8, 1.0 Hz, 1H), 7.34 (d, J = 8.5 Hz, 1H), 7.19 (ddd, J = 7.9, 6.8, 0.8 Hz, 1H), 4.42 (ddd, J = 13.9,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 10.4, 6.1 Hz, 1H), 4.30 (ddd, J = 13.9, 10.6, 5.9 Hz, 1H), 2.76 (dt, J = 12.1, 3.0 Hz, 1H), 2.03– 1.82 (m, 5H), 1.79–1.54 (m, 5H), 1.52–1.43 (m, 4H), 1.43–1.35 (m, 1H), 1.34–1.23 (m, 1H), 1.16 (td, J = 13.4, 4.1 Hz, 1H), 1.04–0.90 (m, 2H), 0.87 (s, 3H), 0.82 (s, 3H), 0.78 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 169.98, 140.40, 132.31, 127.34, 121.05, 119.91, 109.16, 87.69, 56.45, 55.65, 51.20, 41.78, 39.60, 39.30, 38.86, 33.31, 33.14, 26.46, 23.05, 21.41, 20.20, 19.91, 18.29, 15.65. HRMS (ESI-TOF): [M–OAc]+calcd for [C23H32ClN2]+m / z 371.2249, found 371.2262. IR (neat, ATR): νmax 2992, 2950, 2938, 2929, 2871, 2848, 1729, 1467, 1390, 1365, 1337, 1248, 1174, 1126, 1043, 1018, 773, 769, 743 cm–1. Optical Rotation: [α]23 D = –7.00 (c 0.1, CHCl3) M.p.: 118–121 °C.Prepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S45 (114 mg, 1.00 mmol, 2.5 equiv) was used for ozonolysis. MeCN (4 mL) was used to make Solution B. The crude product was purified through FCC to give 45 (Rf= 0.39; hexanes / EtOAc, 4:1) as a pale-yellow oil (79.0 mg, 74% yield). 1H NMR (400 MHz, CDCl3) δ 7.65 (dt, J = 8.2, 0.9 Hz, 1H), 7.41 (ddd, J = 8.5, 6.7, 1.1 Hz, 1H), 7.34 (dt, J = 8.6, 0.8 Hz, 1H), 7.21–7.13 (m, 1H), 4.35 (dd, J = 14.2, 6.9 Hz, 1H), 4.19 (dd, J = 14.2, 7.2 Hz, 1H), 4.02–3.88 (m, 2H), 2.57 (dtd, J = 13.3, 6.9, 5.1 Hz, 1H), 2.01 (s, 3H), 0.97 (d, J = 6.9 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.85, 141.31, 133.02, 127.56, 121.24, 120.93, 119.85, 109.20, 66.42, 51.85, 33.87, 20.80, 14.87. HRMS (ESI-TOF): [M+H]+calcd for [C13H16ClN2O2]+m / z 267.0895, found 267.0894. IR (neat, ATR): νmax 2964, 2933, 2879, 1739, 1617, 1496, 1468, 1393, 1367, 1338, 1236, 1192, 1128, 1051, 1039, 987, 765, 745 cm–1. Optical Rotation: [α]23 D = 6.50 (c 0.2, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using S12 (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S46 (86.1 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 46 (Rf = 0.18; hexanes / EtOAc, 4:1) as a white solid (48.2 mg, 74% yield). 1H NMR (400 MHz, CDCl3) δ 7.75 (dd, J = 5.6, 3.0 Hz, 2H), 7.67 (dd, J = 5.5, 3.0 Hz, 2H), 7.61 (dt, J = 8.2, 1.0 Hz, 1H), 7.35–7.26 (m, 2H), 7.11 (ddd, J = 8.0, 6.5, 1.2 Hz, 1H), 4.62 (t, J = 6.2 Hz, 2H), 4.12 (t, J = 6.2 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 167.75, 141.13, 134.06, 133.82, 131.79, 127.69, 123.34, 121.36, 121.32, 119.95, 108.78, 46.73, 37.35. HRMS (ESI-TOF): [M+H]+calcd for [C17H13ClN3O2]+m / z 326.0691, found 326.0693. IR (neat, ATR): νmax 3067, 3028, 2953, 1773, 1705, 1617, 1467, 1393, 1336, 1265, 1010,745, 717 cm–1. M.p.: 167–170 °C.Prepared following General procedure A using theophylline (72.0 mg, 0.400 mmol, 1.0 equiv), Cu(MeCN)4BF4(25.2 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S47 (175 mg, 1.20 mmol, 3.0 equiv) was used for ozonolysis and MeCN (6 mL) to make Solution B. The crude product was purified through FCC to give 47 (Rf= 0.45; EtOAc) as a pale-yellow oil (88.6 mg, 78% yield). 1H NMR (400 MHz, CDCl3) δ 7.30–7.19 (m, 3H), 7.15 (s, 1H), 7.11–7.03 (m, 2H), 4.47 (t, J = 7.0 Hz, 2H), 3.56 (s, 3H), 3.43 (s, 3H), 3.13 (t, J = 7.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 155.18, 151.71, 149.00, 141.05, 137.05, 128.82, 127.08, 106.61, 48.83, 37.31, 29.81, 28.04.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO HRMS (ESI-TOF): [M+H]+calcd for [C15H17N4O2]+m / z 285.1346, found 285.1345. IR (neat, ATR): νmax 1703, 1657, 1604, 1547, 1475, 1456, 1429, 1407, 1375, 1237, 1221, 1028, 772, 764 cm–1.Prepared following General procedure A using S12 (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S48 (78.1 mg, 0.500 mmol, 2.5 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 48 with small amount of impurities (Rf = 0.14; hexanes / EtOAc, 4:1). The crude material was purified again through FCC to give 48 (Rf= 0.35; toluene / CHCl3 / Et2O, 2:2:1) as a colorless oil (41.2 mg, 73% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 8.2, 0.9 Hz, 1H), 7.39 (dd, J = 4.2, 0.8 Hz, 2H), 7.21–7.13 (m, 1H), 4.66–4.52 (m, 1H), 2.20–2.05 (m, 1H), 1.82 (ddt, J = 13.8, 9.9, 5.7 Hz, 1H), 1.54 (d, J = 6.7 Hz, 3H), 1.51–1.14 (m, 6H), 1.09 (d, J = 6.3 Hz, 6H). 13C NMR (100 MHz, CDCl3) δ 140.60, 132.52, 127.15, 121.06, 120.87, 119.84, 109.31, 70.79, 55.23, 43.32, 36.74, 29.23, 29.14, 21.22, 20.85. HRMS (ESI-TOF): [M–OH]+calcd for [C15H20ClN2]+m / z 263.1310, found 263.1310. IR (neat, ATR): νmax 3377 (br), 3060, 2971, 2935, 2865, 1616, 1495, 1463, 1377, 1337, 1197, 1154, 1120, 768, 742 cm–1.Prepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S49 (128 mg, 1.00 mmol, 2.5 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 49a (Rf = 0.52; toluene / EtOAc / DCM, 2:1:1) as a pale-yellow oil (76.0 mg, 74% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J = 8.2 Hz, 1H), 7.45–7.30 (m, 2H), 7.17 (ddd, J = 7.9, 6.5, 1.1 Hz, 1H), 4.41–4.26 (m, 2H), 3.75–3.57 (m, 2H), 2.01–1.91 (m, 1H), 1.80–1.58 (m, 3H), 1.51–1.39 (m, 1H), 0.98 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 140.64, 132.44, 127.44, 121.15, 120.97, 119.84, 109.27, 60.55, 47.20, 39.41, 36.54, 27.20, 19.60. HRMS (ESI-TOF): [M+H]+calcd for [C13H18ClN2O]+m / z 253.1102, found 253.1102. IR (neat, ATR): νmax3370 (br), 2956, 2931, 2926, 2876, 1617, 1496, 1338, 1176, 1063, 1006, 768, 743 cm–1. Optical Rotation: [α]25 D = –3.00 (c 0.4, CHCl3)Prepared following General procedure A using phthalimide (S18, 29.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (S)-3-Methylhept- 6-en-1-ol (S49, 103 mg, 0.800 mmol, 4.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude reaction mixture was dry-loaded onto SiO2 and purified through FCC (EtOAc / hexanes / Et2O / toluene, 1:1:1.5:1.5) to provide a clear oil (Rf= 0.34; Et2O / toluene, 1.85:1) that was recrystallized (pentanes) to provide 49b as a white solid (36.6 mg, 74% yield). 1H NMR (500 MHz, CDCl3) δ 7.81 (dd, J = 5.4, 3.1 Hz, 2H), 7.68 (dd, J = 5.5, 3.1 Hz, 2H), 3.84–3.56 (m, 4H), 1.83–1.58 (m, 4H), 1.52 (dq, J = 13.3, 6.9, 6.4 Hz, 1H), 1.41 (dq, J = 13.0, 6.5 Hz, 1H), 0.98 (d, J = 6.3 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 168.50, 133.89, 132.11, 123.18, 60.65, 39.34, 36.06, 35.61, 27.20, 19.46. HRMS (ESI-TOF): [M+H]+calcd for [C14H18NO3]+m / z 248.1281, found 248.1282. IR (neat, ATR): νmax 3413 (brs), 2955, 2930, 2872, 1772, 1714, 1400, 1373, 1173, 1061 cm–1. Optical Rotation: [α]26 D = –4.00 (c 0.2, CHCl3). M.p.: 53–55 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S50 (147 mg, 0.800 mmol, 2.0 equiv) and MeCN (4 mL) were used to make Solution B. The crude product was purified through FCC to give 50 (Rf = 0.35; Et2O / CHCl3 / DCM / toluene, 1:1:3:5) as a pale- yellow oil (66.7 mg, 54% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.48–7.33 (m, 2H), 7.24–7.14 (m, 1H), 4.51–4.37 (m, 2H), 4.12 (dd, J = 12.2, 4.2 Hz, 1H), 3.95 (dd, J = 12.2, 6.8 Hz, 1H), 2.73 (dd, J = 6.8, 4.2 Hz, 1H), 2.25–2.07 (m, 2H), 2.03 (s, 3H), 1.34 (s, 3H). 13C NMR 13C NMR (100 MHz, CDCl3) δ 170.70, 140.67, 132.99, 127.68, 121.38, 121.14, 119.95, 109.12, 62.91, 59.52, 58.62, 45.10, 37.91, 20.72, 16.94. HRMS (DART): [M+H]+calcd for [C15H18ClN2O3]+m / z 309.1000, found 309.1001. IR (neat, ATR): νmax3064, 2994, 2947, 1617, 1497, 1468, 1375, 1338, 1176, 1038, 766, 746 cm–1. Optical Rotation: [α]25 D = 9.82 (c 0.56, CHCl3)Prepared following General procedure A using S12 (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S51 (56.1 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 51 (Rf= 0.47; hexanes / EtOAc, 40:1) with a little amount of impurities. This impure material was purified again through FCC to give pure 51 (Rf = 0.36; hexanes / toluene, 5:2) as a colorless oil (35.4 mg, 67% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 8.2, 0.8 Hz, 1H), 7.45–7.32 (m, 2H), 7.18 (ddd, J = 7.9, 6.5, 1.1 Hz, 1H), 4.30 (t, J = 7.2 Hz, 2H), 1.90 (p, J = 7.3 Hz, 2H), 1.37–1.17 (m, 10H), 0.86 (t, J = 6.9 Hz, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (100 MHz, CDCl3) δ 140.77, 132.35, 127.26, 121.00, 120.96, 119.79, 109.34, 49.32, 31.76, 29.82, 29.15, 29.11, 26.80, 22.62, 14.08. HRMS (ESI-TOF): [M+H]+calcd for [C15H22ClN2]+m / z 265.1466, found 265.1473. IR (neat, ATR): νmax3063, 2953, 2925, 2854, 1617, 1495, 1467, 1336, 1173, 1125, 1005, 982, 766, 740 cm–1.Prepared following General procedure A using S18 (58.8 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.9- mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S52 (130.4 mg, 0.8 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 52 (Rf = 0.51; hexanes / EtOAc, 3:1) as a colorless oil (61.4 mg, 55% yield). 1H NMR (400 MHz, CDCl3) δ 7.84 (td, J = 5.3, 2.1 Hz, 2H), 7.76–7.68 (m, 2H), 3.72 (t, J = 6.7 Hz, 2H), 3.44 (t, J = 6.4 Hz, 2H), 1.96–1.80 (m, 4H). 13C NMR (100 MHz, CDCl3) δ 168.38, 134.00, 132.05, 123.28, 36.97, 32.80, 29.85, 27.26. HRMS (DART): [M+H]+calcd for [C12H13BrNO2]+m / z 282.0124, found 282.0124. IR (neat, ATR): νmax2939, 2868, 1770, 1703, 1436, 1394, 1371, 1359, 1256, 1188, 1086, 1023, 716, 529 cm–1.Prepared following General procedure B using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene S53 (248 mg, 0.800 mmol, 2.0 equiv) was dissolved in MeOH (4 mL) and DCM (20 mL) for ozonolysis. MeCN (6 mL) and benzene (4 mL) were used to make Solution B. The crude product was purified through FCC to give 53 (Rf= 0.25; hexanes / EtOAc, 40:1) as a white solid (113.0 mg, 65% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.2 Hz, 1H), 7.47–7.35 (m, 2H), 7.20 (ddd, J = 7.9, 6.6, 1.0 Hz, 1H), 7.11 (s, 4H), 4.42–4.28 (m, 2H), 2.42 (tt, J = 12.1, 3.3 Hz, 1H), 2.33 (s, 3H), 1.97–1.72 (m, 10H), 1.51–1.35 (m, 2H), 1.30–0.93 (m, 9H). 13C NMR (100 MHz, CDCl3) δ 144.86, 140.65, 135.21, 132.32, 128.98, 127.28, 126.69, 121.04, 119.84, 109.30, 47.30, 44.23, 43.22, 42.85, 37.14, 35.48, 34.69, 33.34, 30.41, 29.84, 21.02. HRMS (ESI-TOF): [M+H]+calcd for [C28H36ClN2]+m / z 435.2562, found 435.2561. IR (neat, ATR): νmax 2918, 2849, 1617, 1514, 1495, 1467, 1446, 1336, 1174, 980, 812, 767, 742 cm–1. M.p.: 115–118 °C.Prepared following General procedure B using S12 (15.3 mg, 0.100 mmol, 1.0 equiv), copper(I) chloride (2.00 mg, 0.0200 mmol, 20 mol %), 1,10-phenanthroline (3.6 mg, 0.0800 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. The alkene S54 (52.5 mg, 0.200 mmol, 2.0 equiv) was dissolved in MeOH (1 mL) and DCM (10 mL) for ozonolysis. MeCN (1 mL) and benzene (3 mL) were used to make Solution B. The crude product was purified through FCC to give 54-major (Rf = 0.43; hexanes / toluene, 4:1) as a white solid (12.5 mg, 32% yield) and 54-minor (Rf= 0.56; hexanes / toluene, 4:1) as a white solid (9.6 mg, 25% yield).1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 8.2 Hz, 1H), 7.48–7.33 (m, 2H), 7.17 (ddd, J = 7.9, 6.2, 1.4 Hz, 1H), 4.31 (tt, J = 10.4, 6.6 Hz, 1H), 2.12–1.98 (m, 4H), 1.97–1.87 (m, 2H), 1.76 (t, J = 12.4 Hz, 4H), 1.37–1.20 (m, 9H), 1.19–1.07 (m, 4H), 1.02 (qd, J = 12.6, 11.6, 3.4 Hz, 2H), 0.93–0.81 (m, 5H). 13C NMR (100 MHz, CDCl3) δ 140.05, 132.12, 126.94, 120.98, 119.79, 109.44, 58.79, 43.03, 42.22, 37.87, 37.45, 33.58, 32.44, 32.25, 30.16, 29.15, 26.69, 22.74, 14.14. HRMS (DART): [M+H]+calcd for [C24H36ClN2]+m / z 387.2562, found 387.2555Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax2921, 2851, 1616, 1494, 1465, 1449, 1337, 1194, 1005, 990, 765, 742 M.p.: 73–74 °C.1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.46–7.34 (m, 2H), 7.18 (ddd, J = 7.9, 5.3, 2.4 Hz, 1H), 4.44 (tt, J = 9.3, 4.0 Hz, 1H), 2.26–2.09 (m, 2H), 2.04–1.93 (m, 2H), 1.93–1.86 (m, 2H), 1.86–1.70 (m, 4H), 1.62–1.39 (m, 3H), 1.35–1.21 (m, 7H), 1.21–1.07 (m, 3H), 0.97–0.77 (m, 7H). 13C NMR (100 MHz, CDCl3) δ 140.11, 131.92, 126.91, 120.98, 120.95, 119.76, 109.50, 57.65, 39.14, 37.69, 37.44, 36.68, 33.37, 32.27, 30.94, 28.34, 26.70, 26.66, 22.75, 14.15. HRMS (DART): [M+H]+calcd for [C24H36ClN2]+m / z 387.2562, found 387.2558 IR (neat, ATR): νmax2951, 2921, 2870, 2851, 1616, 1493, 1464, 1447, 1337, 1188, 764, 743 cm–1. M.p.: 73–74 °C.Prepared following General procedure B using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. Phytol (237 mg, 0.800 mmol, 2.0 equiv), MeOH (2 mL), and DCM (10 mL) were used for ozonolysis. When the ozonolysis was complete, the ozonolysis mixture was diluted with DCM (70 mL). The solution was filtered through silica gel (50 g) and washed with DCM / MeOH (40:1, 100 mL) and then the filtrate was concentrated. The residue was treated with MeCN (8 mL) to make Solution B. The crude product was purified through FCC to give 55a (Rf = 0.28; hexanes / EtOAc, 60:1) as a colorless oil (116.0 mg, 77% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.46–7.32 (m, 2H), 7.18 (ddd, J = 7.8, 6.5, 1.1 Hz, 1H), 4.29 (t, J = 7.3 Hz, 2H), 2.02–1.80 (m, 2H), 1.52 (dp, J = 13.2, 6.6 Hz, 1H), 1.45–1.00 (m, 16H), 0.90–0.78 (m, 12H). 13C NMR (100 MHz, CDCl3) δ 140.75, 132.36, 127.26, 121.00, 120.97, 119.80, 109.34, 49.63, 39.38, 37.36, 37.28, 37.16, 33.94, 32.78, 32.49, 28.00, 27.40, 24.81, 24.42, 22.75, 22.65, 19.74, 19.61. HRMS (ESI-TOF): [M+H]+calcd for [C23H38ClN2]+m / z 377.2718, found 377.2717. IR (neat, ATR): νmax 2953, 2926, 2867, 1617, 1496, 1467, 1376, 1337, 1174, 1126, 1006, 767, 742 cm–1. Optical Rotation: [α]25 D = –1.17 (c 0.2, CHCl3)Prepared following General procedure A using S18 (101 mg, 0.689 mmol, 1.0 equiv), copper(I) chloride (13.6 mg, 0.137 mmol, 20 mol %), 1,10-phenanthroline (24.9 mg, 0.137 mmol, 20 mol %), and MeCN (10 mL) to make Solution A. Phytol (297 mg, 1.00 mmol, 2.0 equiv), MeOH (3 mL), and DCM (15 mL) were used for ozonolysis. When the ozonolysis was complete, the ozonolysis mixture was diluted with DCM (100 mL). The solution was filtered through silica gel (50 g) and washed with DCM / MeOH (40:1, 100 mL) and then the filtrate was concentrated. The residue was treated with MeCN (10 mL) to make Solution B. The crude product was purified through FCC to give 55b (Rf = 0.58; hexanes / EtOAc, 9:1) as a colorless oil (white foam) (205.0 mg, 80% yield). 1H NMR (500 MHz, CDCl3) δ 7.85–7.76 (m, 2H), 7.72–7.64 (m, 2H), 3.63 (t, J = 7.5 Hz, 2H), 1.75–1.56 (m, 2H), 1.49 (dp, J = 13.3, 6.6 Hz, 1H), 1.41 (dt, J = 12.3, 6.2 Hz, 1H), 1.38–1.27 (m, 3H), 1.27–1.07 (m, 9H), 1.07–0.97 (m, 3H), 0.87–0.81 (m, 9H), 0.80 (d, J = 6.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.38, 133.77, 132.20, 123.10, 39.35, 38.36, 37.36, 37.26, 37.23, 34.03, 32.75, 32.51, 27.96, 26.20, 24.78, 24.43, 22.72, 22.62, 19.71, 19.57. HRMS (DART): [M+H]+calcd for [C24H38NO2]+m / z 373.2898, found 373.2895. IR (neat, ATR): νmax 2953, 2926, 2868, 1776, 1717, 1467, 1396, 1370 cm–1. Optical Rotation: [α]25 D = 1.00 (c 0.2, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure A using S12 (76.3 mg, 0.500 mmol, 1.0 equiv), copper(I) chloride (9.90 mg, 0.100 mmol, 20 mol %), 1,10-phenanthroline (18.0 mg, 0.100 mmol, 20 mol %), and MeCN (5 mL) to make Solution A. (–)-β-Pinene (136 mg, 1.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (5 mL) to make Solution B. The crude product was purified through FCC to give 56a (Rf= 0.59; hexanes / EtOAc, 4:1) as a pale-yellow oil (70.0 mg, 44% yield) and 57b (Rf = 0.53; hexanes / EtOAc, 4:1) as a pale-yellow oil (42.0 mg, 26% yield).1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 8.2, 1.0 Hz, 1H), 7.41 (ddd, J = 8.5, 6.8, 1.1 Hz, 1H), 7.34 (dt, J = 8.6, 0.8 Hz, 1H), 7.22–7.14 (m, 1H), 4.28–4.15 (m, 2H), 3.64 (s, 3H), 2.71–2.62 (m, 1H), 2.07–1.77 (m, 5H), 1.16 (s, 3H), 0.92 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 173.24, 140.63, 132.55, 127.40, 121.11, 121.02, 119.86, 109.17, 51.19, 47.40, 46.00, 42.56, 39.70, 30.37, 30.17, 24.32, 17.72. HRMS (DART): [M+H]+calcd for [C17H22ClN2O2]+m / z 321.1364, found 321.1365. IR (neat, ATR): νmax2951, 2924, 2854, 1732, 1617, 1496, 1467, 1436, 1385, 1370, 1338, 1235, 1194, 1176, 767, 743 cm–1. Optical Rotation: [α]26 D = 6.33 (c 0.1, CHCl3).1H NMR (400 MHz, CDCl3) major: δ 7.65 (dq, J = 8.1, 1.0 Hz, 0.75×1H), 7.43–7.29 (m, 0.75×2H), 7.22–7.13 (m, 0.75×1H), 4.53 (dd, J = 9.7, 8.1 Hz, 0.75×1H), 3.69 (s, 0.75×3H), 2.81 (q, J = 10.6 Hz, 0.75×1H), 2.48 (dt, J = 11.2, 7.8 Hz, 0.75×1H), 2.41–2.22 (m, 0.75×2H), 2.00–1.65 (m, 0.75×3H), 1.29 (s, 0.75×3H), 1.23 (s, 1H), 0.70 (s, 0.75×2H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (100 MHz, CDCl3) major: δ 173.86, 141.02, 132.22, 127.22, 121.37, 121.25, 119.71, 109.58, 59.17, 51.60, 45.39, 38.31, 32.23, 29.52, 27.45, 25.34, 15.90. 1H NMR (400 MHz, CDCl3) minor: δ 7.65 (dq, J = 8.1, 1.0 Hz, 0.25×1H), 7.43–7.29 (m, 0.25×2H), 7.22–7.13 (m, 0.25×1H), 4.66 (dd, J = 8.1, 6.5 Hz, 0.25×1H), 3.69 (s, 0.25×3H), 3.21 (tdd, J = 11.4, 7.7, 4.5 Hz, 0.25×1H), 2.41–2.22 (m, 0.25×2H), 2.22–2.09 (m, 0.25×2H), 2.00–1.65 (m, 0.25×3H), 1.23 (s, 0.25×3H), 0.69 (s, 0.25×3H). 13C NMR (100 MHz, CDCl3) minor: δ 174.02, 141.38, 132.26, 127.20, 121.30, 121.22, 119.71, 109.51, 59.78, 51.63, 43.56, 39.45, 32.48, 26.88, 26.34, 23.40, 23.28. HRMS (DART): [M+H]+calcd for [C17H22ClN2O2]+m / z 321.1364, found 321.1364. IR (neat, ATR): νmax2952, 2924, 28533, 1739, 1616, 1493, 1465, 1438, 1370, 1340, 1221, 1175, 768, 744 cm–1. Optical Rotation: [α]25 D = 21.44 (c 0.1, CHCl3).Prepared following General procedure A using phthalimide (29.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A. (–)-β-Pinene (54.5 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis. After evaporation of MeOH in vacuo, the remaining residue had the smell of an artificial berry. MeCN (2 mL) was used to make Solution B. The crude product was dry-loaded onto SiO2 and purified through FCC (Et2O / toluene, from 0 to 5%) to provide a 3.1:1 ratio of regioisomers, with 57b present as an inseparable mixture of diastereoisomers (ratio of 3.5:1), as determined by1H NMR spectroscopy with 1,3,5- trimethoxybenzene (33.6 mg, 0.2 mmol) as an internal standard. 56b (Rf = 0.52; EtOAc / hexanes, 1:3) and 57b (Rf= 0.54; EtOAc / hexanes, 1:3) were obtained as clear oils (56b: 33.0 mg, 53% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (500 MHz, CDCl3) δ 7.86–7.81 (m, 2H), 7.73–7.67 (m, 2H), 3.67–3.53 (m, 5H), 2.75–2.64 (m, 1H), 2.07–2.00 (m, 1H), 1.98–1.85 (m, 2H), 1.77–1.69 (m, 1H), 1.67–1.57 (m, 1H), 1.18 (s, 3H), 0.92 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 173.31, 168.33, 133.90, 132.12, 123.19, 51.16, 46.08, 42.60, 39.96, 36.33, 30.21, 29.26, 24.49, 17.52. HRMS (DART): [M+H]+calcd for [C18H22NO4]+m / z 316.1543, found 316.1544. IR (neat, ATR): νmax2952, 2869, 1714, 1436, 1398, 1195, 1088, 1034 cm–1. Optical Rotation: [α]27 D = 8.15 (c 0.27, MeOH).1H NMR (500 MHz, CD3CN) major: δ 7.83–7.70 (m, 0.72×4H), 4.13 (dd, J = 10.5, 8.4 Hz, 0.72×1H), 3.62 (s, 0.72×3H), 3.01 (q, J = 10.6 Hz, 0.72×1H), 2.25 (t, J = 7.8 Hz, 0.72×2H), 2.15 (d, J = 8.2 Hz, 0.72×2H), 1.78–1.67 (m, 0.72×1H), 1.68–1.59 (m, 0.72×1H), 1.15 (s, 0.72×3H), 0.96 (s, 0.72×3H). 13C NMR (125 MHz, CD3CN) major: δ 173.61, 169.40, 134.08, 131.87, 122.62, 52.88, 50.95, 45.37, 39.52, 31.82, 28.63, 25.86, 25.20, 15.93. 1H NMR (500 MHz, CD3CN) minor: δ 7.83–7.70 (m, 0.28×4H), 4.37–4.27 (m, 0.28×1H), 3.62 (s, 0.28×3H), 3.29 (ddd, J = 12.0, 9.3, 5.4 Hz, 0.28×1H) 2.25 (t, J = 7.8 Hz, 0.28×2H), 2.15 (d, J = 8.2 Hz, 0.28×2H), 1.78–1.67 (m, 0.28×1H), 1.68–1.59 (m, 0.28×1H), 1.10 (s, 0.28×3H), 1.00 (s, 0.28×3H),. 13C NMR (125 MHz, CD3CN) minor: δ 173.69, 169.21, 134.11, 131.87, 122.68, 53.14, 50.95, 43.02, 40.07, 31.98, 25.84, 24.36, 23.73, 22.61. HRMS (DART): [M+H]+calcd for [C18H22NO4]+m / z 316.1543, found 316.1541. IR (neat, ATR): νmax 2952, 2869, 1736, 1612, 1467, 1370, 1173, 1089, 1051, 1017 cm–1. Optical Rotation: [α]27 D = 11.15 (c 0.52, MeOH).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Prepared following General procedure A using S12 (76.3 mg, 0.500 mmol, 1.0 equiv), copper(I) chloride (9.90 mg, 0.100 mmol, 20 mol %), 1,10-phenanthroline (18.0 mg, 0.100 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. (±)-Sabinene (136 mg, 1.00 mmol, 2 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 58 (Rf = 0.63; hexanes / EtOAc, 4:1) as a pale-yellow oil (124.5 mg, 78% yield). 1H NMR (500 MHz, CDCl3)δ 7.64 (d, J = 8.2 Hz, 1H), 7.47–7.38 (m, 2H), 7.17 (ddd, J = 7.9, 6.4, 1.2 Hz, 1H), 4.42 (ddd, J = 13.9, 10.3, 6.1 Hz, 1H), 4.27 (ddd, J = 13.9, 10.4, 6.0 Hz, 1H), 3.67 (s, 3H), 2.18–2.04 (m, 2H), 1.62 (dd, J = 8.3, 5.7 Hz, 1H), 1.45 (hept, J = 6.8 Hz, 1H), 1.15–1.09 (m, 1H), 1.00–0.95 (m, 4H), 0.93 (d, J = 6.9 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 173.23, 140.50, 132.28, 127.36, 121.07, 121.04, 119.66, 109.60, 51.82, 48.10, 34.50, 33.52, 27.71, 24.36, 19.45, 19.28, 18.97. HRMS (DART): [M+H]+calcd for [C17H22ClN2O2]+m / z for 321.1364, found 321.1364 IR (neat, ATR): νmax 2959, 2879, 1725, 1618, 1496, 1468, 1438, 1390, 1338, 1194, 1174, 766, 746 cm–1.Prepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene 59 (119 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 60 (Rf = 0.29; toluene) as a colorless oil (68.9 mg, 52% yield). 1H NMR (400 MHz, CDCl3) δ 7.64 (dt, J = 8.2, 0.9 Hz, 1H), 7.47 (d, J = 8.6 Hz, 1H), 7.44–7.35 (m, 1H), 7.17 (ddd, J = 8.0, 6.7, 0.9 Hz, 1H), 4.83 (tt, J = 12.2, 4.8 Hz, 1H), 3.73 (s, 3H), 2.64 (tt, J = 11.5, 6.6 Hz, 1H), 2.41–2.32 (m, 2H), 2.32–2.21 (m, 2H), 2.17 (td, J = 13.0, 3.6 Hz, 2H), 1.94–1.83 (m, 2H), 1.76–1.63 (m, 3H), 1.40 (dt, J = 13.1, 2.2 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 177.10, 140.23, 132.28, 127.15, 121.17, 120.93, 119.75, 109.36, 51.86, 50.98, 38.70, 35.48, 29.48, 28.31, 25.61. HRMS (DART): [M+H]+calcd for [C18H22ClN2O2]+m / z 333.1364, found 333.1362Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax2948, 2924, 2870, 1731, 1616, 1494, 1466, 1337, 1298, 1280, 1222, 1192, 1174, 743 cm–1.Prepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. The alkene 61 (201 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 62 (Rf= 0.45; toluene / Et2O, 10:1) as a white solid (141.7 mg, 81% yield). 1H NMR (400 MHz, CDCl3) δ 7.67–7.59 (m, 3H), 7.53 (d, J = 8.6 Hz, 1H), 7.50–7.42 (m, 1H), 7.27–7.17 (m, 3H), 4.58 (t, J = 6.5 Hz, 2H), 3.60 (s, 3H), 3.53 (t, J = 6.5 Hz, 2H), 3.30 (t, J = 14.8, 2H), 2.40 (s, 3H), 2.30 (t, J = 14.8, 2H). 13C NMR (100 MHz, CDCl3) δ 171.39, 143.86, 141.45, 135.28, 133.59, 129.86, 128.01, 127.20, 121.55, 120.98, 119.64, 109.70, 51.83, 48.96, 48.86, 45.91, 33.69, 21.54. HRMS (DART): [M+H]+calcd for [C20H23ClN3O4S]+m / z 436.1092, found 436.1091. IR (neat, ATR): νmax 2954, 1737, 1619, 1599, 1497, 1468, 1438, 1338, 1258, 1205, 1160, 1090, 816, 766, 747 cm–1. M.p.: 83–85 °C.Prepared following General procedure B using S12 (30.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeCN (2 mL) to make Solution A.63 (64.9 mg, 0.400 mmol, 2.0 equiv), MeOH (4 mL), and DCM (10 mL) were used for ozonolysis. When ozonolysis was complete, DCM (150 mL) was added to dilute the ozonolysis mixture. The mixture was filtered through silica gel (50 g) and washed with DCM / MeOH (40:1, 400 mL) and then the filtrate was concentrated. The residue was treated with MeCN (2 mL) to make Solution B. The crudeAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO product was purified through FCC to give 64 (Rf= 0.44; hexanes / EtOAc, 4:1) as a colorless oil (55.9 mg, 88% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (dt, J = 8.2, 1.0 Hz, 1H), 7.48–7.34 (m, 2H), 7.20 (ddd, J = 8.2, 6.7, 1.0 Hz, 1H), 4.59–4.46 (m, 2H), 3.67 (s, 3H), 2.58–2.41 (m, 4H), 2.27–2.11 (m, 2H). 13C NMR (100 MHz, CDCl3) δ 172.50, 140.78, 133.36, 127.75, 122.97, 121.44 (t, J = 240.5 Hz), 121.13, 119.89, 109.17, 51.96, 42.38 (t, J = 5.7 Hz), 36.42 (t, J = 24.7 Hz), 32.11(t, J = 25.2 Hz), 26.79 (t, J = 4.8 Hz). HRMS (DART): [M+H]+calcd for [C14H16ClF2N2O2]+m / z 317.0863, found 317.0863. IR (neat, ATR): νmax2953, 1739, 1618, 1497, 1469, 1439, 1337, 1202, 1178, 1130, 932, 767, 744 cm–1. 4.4 Synthesis of chiral aminesThe ammonium chloride 65 was synthesized according to a literature procedure (80). The phthalimide 55b (186 mg, 0.500 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (10 mL) and heated under reflux for 3 h. The reaction mixture was concentrated and DCM (10 mL) was added. The resulting suspension was filtered and the filtrate concentrated. The residue was acidified (pH < 2) by adding 1.0 M HCl and extracted twice with DCM. The organic phase was washed with brine, dried (Na2SO4), and concentrated. The residue was purified through FCC (Rf= 0.56; MeOH / EtOAc, 1:10) to give 65 as an off-white solid (85.5 mg, 75% yield). 1H NMR (500 MHz, CDCl3) δ 8.21 (brs, 3H), 2.96 (h, J = 12.7 Hz, 2H), 1.89–1.61 (m, 2H), 1.51 (dp, J = 13.1, 6.6 Hz, 1H), 1.44–1.31 (m, 3H), 1.31–1.09 (m, 10H), 1.09–0.98 (m, 3H), 0.91–0.75 (m, 12H). 13C NMR (125 MHz, CDCl3) 40.34, 39.37, 37.39, 37.30, 37.27, 33.82, 32.83, 32.39, 27.98, 25.33, 24.81, 24.49, 22.74, 22.64, 19.72, 19.38. HRMS (DART): [M–Cl]+calcd for [C16H36N]+m / z 242.2842, found 242.2840. IR (neat, ATR): νmax3429 (br), 2958, 2925, 2870, 2852, 1610, 1509, 1468, 1380, 1259 cm–1.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Optical Rotation: [α]26 D = 0.50 (c 0.2, CH2Cl2). M.p.: 69–72 °C.The ammonium salt 66 was synthesized according to a literature procedure (80). The phthalimide 18 (130 mg, 0.500 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (5 mL). After the mixture had stirred for 0.5 h at room temperature, 5% HCl (2 mL) was added and the reaction mixture was stirred for an additional 12 h. The resulting suspension was filtered and then the filtrate was diluted with an equal amount of water, acidified (pH < 2), and washed with DCM. The organic phase was discarded. The aqueous phase was basified with solid KOH (pH >10) and then extracted with ether (2 × 15 mL). The combined ethereal layers were washed with brine, dried (Na2SO4), and concentrated. The residue was dissolved in DCM (5 mL) and the insoluble solid removed through filtration. The filtrate was concentrated to give the off-white solid, which was washed with cool pentane to give 66 as an off-white solid (51.1 mg, 79% yield). 1H NMR (400 MHz, CDCl3) δ 3.23–3.03 (m, 1H), 2.37 (t, J = 7.4 Hz, 1H), 2.15–1.68 (m, 5H), 1.63 (d, J = 13.0 Hz, 1H), 1.51 (ttt, J = 12.9, 6.5, 3.4 Hz, 1H), 1.14 (qd, J = 13.0, 3.5 Hz, 1H), 1.04–0.84 (m, 5H). 13C NMR (125 MHz, CDCl3) δ 75.55, 56.89, 42.13, 34.63, 33.83, 31.43, 22.00. HRMS (DART): [M+H]+calcd for [C7H16NO]+m / z 130.1226, found 130.1223. IR (neat, ATR): νmax3288 (br), 2950, 2925, 2867, 2854, 1581, 1456, 1048 cm–1. Optical Rotation: [α]25 D = –17.00 (c 0.1, CH2Cl2). M.p.: 76–78 °C.The phthalimide 34b (71.6 mg, 0.260 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (3 mL). After heating under reflux for 1 h, the reaction mixture wasAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO concentrated in vacuo. The residue was purified through silica gel FCC (Rf= 0.38; 7 N NH3in MeOH solution / DCM, 2:5) to afford 67 as a yellow solid (27.8 mg, 74% yield). 1H NMR (500 MHz, CD3OD) δ 3.56 (t, J = 3.3 Hz, 1H), 3.00 (tt, J = 9.9, 4.8 Hz, 1H), 1.86–1.66 (m, 3H), 1.66–1.58 (m, 1H), 1.58–1.45 (m, 2H), 1.19 (s, 3H). 13C NMR (125 MHz, CD3OD) δ 73.06, 70.02, 44.27, 37.20, 31.92, 29.54, 25.33. HRMS (DART): [M+H]+calcd for [C7H16NO2]+m / z 146.1176, found 146.1175. IR (neat, ATR): νmax3341 (br), 3289 (br), 2927, 2869, 1634, 1598, 1563, 1454, 1376, 1181, 1133, 1042 cm–1. Optical Rotation: [α]27 D = 12.50 (c 0.2, MeOH). M.p.: 137–140 °C.The phthalimide 49b (170 mg, 0.690 mmol) was dissolved in 0.2 M methanolic hydrazine hydrate (10 mL). After heating under reflux for 5 h, the reaction mixture was concentrated in vacuo. DCM (10 mL) was added to the residue and the resulting suspension was filtered. The filtrate was concentrated and the residue purified through silica gel FCC (Rf= 0.29; 7 N NH3 in MeOH solution / DCM, 1:5) to give a yellow oil. DCM (5 mL) was added and the resulting suspension was filtered to remove the silica that had dissolved in the eluent. The DCM solution was concentrated to afford 68 as a yellow oil (64.1 mg, 80% yield). 1H NMR (400 MHz, CD3OD) δ 3.64–3.51 (m, 2H), 2.83–2.44 (m, 2H), 1.69–1.43 (m, 3H), 1.39–1.25 (m, 2H), 0.90 (d, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 60.66, 40.37, 39.90, 39.81, 27.22, 20.19. HRMS (DART): [M+H]+calcd for [C6H16NO]+m / z 118.1226, found 118.1226. IR (neat, ATR): νmax 3315 (br), 2957, 2925, 2871, 1565, 1469, 1383, 1324, 1088, 883 cm–1. Optical Rotation: [α]25 D = –3.50 (c 0.2, CH2Cl2).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO A round-bottom flask was charged with a stirrer bar, the ester 55b (78.8 mg, 0.250 mmol), and of 0.5 M hydrazine (2.2 equiv) in MeOH (1.1 mL). The mixture was heated under reflux. After 45 min [when the starting material was fully consumed (TLC)], the reaction mixture was allowed to cool and the solvent was evaporated in vacuo. The residue was treated with minimal MeOH to form a homogenous solution, which was dry-loaded onto a SiO2 column and subjected to FCC to obtain 69 (Rf = 0.41; DCM / 7 N NH3 in MeOH, 12:1) as a clear oil (33.5 mg, 72% yield). 1H NMR (400 MHz, CDCl3) δ 3.62 (s, 3H), 2.74–2.41 (m, 3H), 2.04–1.76 (m, 3H), 1.48 (dq, J = 14.1, 7.8, 7.0 Hz, 1H), 1.35 (dq, J = 14.4, 8.1 Hz, 1H), 1.24–1.13 (m, 4H), 0.88 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 173.46, 1.09, 46.08, 42.67, 40.38, 40.06, 34.59, 30.25, 24.59, 17.51. HRMS (DART): [M+H]+calcd for [C10H20NO2]+m / z 186.1489, found 186.1495. IR (neat, ATR): νmax3305 (br), 2952, 2926, 2872, 1732, 1574, 1463, 1435, 1324, 1195, 1178 Optical Rotation: [α]27 D = –1.60 (c 0.25, MeOH).A 20-mL vial was equipped with a stirrer bar and charged with sodium hydroxide (400 mg, 10.0 mmol) and ethanol (12 mL) to form a solution (0.83 M). An 8-mL Schlenk tube was charged with the phthalimide (+)-36b-minor (88.1 mg, 0.340 mmol, 1.0 equiv) and 2- mercaptopyridine (128 mg, 1.15 mmol, 3.0 equiv) and then capped with a stopper. The reaction vessel was purged with argon three times before the NaOH solution (0.41 mL, 1.0 equiv) and ethanol (1.6 mL) were added. The reaction vessel was stirred at 50 °C for 12 h and then EtOAc (5 mL) was added. This mixture was washed with sat. aqueous NH4Cl (2 × 10 mL) and brine (10 mL). The organic phase was dried (Na2SO4) and filtered. Evaporation of all volatiles under reduced pressure and purification of the residue through FCC (Rf = 0.42; hexanes / EtOAc, 1:1) yielded 70 as a pale-yellow solid (93.0 mg, 73% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO1H NMR (500 MHz, CDCl3) δ 8.37 (ddd, J = 4.9, 1.8, 0.9 Hz, 1H), 7.85–7.74 (m, 2H), 7.72–7.64 (m, 2H), 7.51–7.42 (m, 1H), 7.20 (dt, J = 8.1, 0.8 Hz, 1H), 6.96 (ddd, J = 7.3, 4.9, 1.0 Hz, 1H), 4.57 (tt, J = 12.1, 4.2 Hz, 1H), 4.45 (q, J = 3.5 Hz, 1H), 3.27 (ddd, J = 13.3, 12.2, 4.0 Hz, 1H), 2.60 (qd, J = 12.7, 4.7 Hz, 1H), 2.12 (s, 1H), 1.92–1.73 (m, 3H), 1.68–1.57 (m, 1H), 1.41 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 168.31, 157.86, 149.27, 136.06, 133.81, 131.99, 123.07, 123.02, 119.70, 71.39, 49.81, 46.54, 35.10, 31.03, 28.44, 24.73. HRMS (DART): [M+H]+calcd for [C20H21N2O3S]+m / z 369.1267, found 369.1267. IR (neat, ATR): νmax 3471 (br), 3057, 2964, 2928, 2868, 1709, 1579, 1376, 1122, 1085 cm–1. Optical Rotation: [α]26 D = 64.00 (c 0.2, CH2Cl2). M.p.: 183–185 °C.The phthalimide 70 (73.6 mg, 0.2 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (2 mL). After heating under reflux for 1 h, the reaction mixture was concentrated in vacuo. DCM (10 mL) was added to the residue and the resulting suspension was filtered. The filtrate was concentrated and the residue was purified through silica gel FCC (Rf= 0.46; 7 N NH3 in MeOH / DCM, 1:10) to give an off-white solid. DCM (2 mL) was added and the resulting suspension was filtered to remove silica that had dissolved in the eluent. The DCM solution was concentrated to afford 71 as an off-white solid (43.4 mg, 91% yield). 1H NMR (500 MHz, CDCl3) δ 8.34 (ddd, J = 5.0, 1.8, 0.9 Hz, 1H), 7.46 (ddd, J = 8.1, 7.4, 1.9 Hz, 1H), 7.22 (dt, J = 8.1, 1.0 Hz, 1H), 6.98 (ddd, J = 7.3, 5.0, 1.0 Hz, 1H), 4.15 (dd, J = 11.4, 4.0 Hz, 1H), 3.33–3.14 (m, 1H), 1.98 (dtd, J = 13.6, 4.3, 1.8 Hz, 1H), 1.91 (td, J = 13.3, 4.3 Hz, 1H), 1.86–1.73 (m, 2H), 1.70–1.61 (m, 1H), 1.61–1.52 (m, 1H), 1.26 (s, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (125 MHz, CDCl3) δ 159.16, 148.80, 136.35, 122.90, 119.83, 72.42, 50.22, 46.05, 38.67, 35.47, 30.70, 22.79. HRMS (DART): [M+H]+calcd for [C12H19N2OS+]+m / z 239.1213, found 239.1213. IR (neat, ATR): νmax3253 (br), 2929, 2869, 1579, 1453, 1414, 1121 cm–1. Optical Rotation: [α]25 D = 28.50 (c 0.2, CH2Cl2). M.p.: 127–128 °C.CeCl3·H2O (196 mg, 0.520 mmol) was added to a stirred solution of the enone 31b (163 mg, 0.500 mmol) in EtOH (5 mL) while cooling in an ice bath. NaBH4(37.8 mg, 1.00 mmol) was added slowly. After 10 min, the reaction was quenched through the addition of aq. NH4Cl (10 mL). The aqueous phase was extracted with DCM three times. The combined organics were washed with brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified through silica gel FCC (Rf= 0.25; EtOAc / hexanes, 3:7) to furnish 72 as a white foam (99.1 mg, 61% yield).1H NMR (500 MHz, CDCl3) δ 7.81 (dd, J = 5.2, 3.1 Hz, 2H), 7.69 (dd, J = 5.3, 3.1 Hz, 2H), 5.41 (s, 1H), 4.50 (tt, J = 12.6, 3.6 Hz, 1H), 4.34–4.24 (m, 1H), 2.43 (t, J = 13.6 Hz, 1H), 2.35–2.19 (m, 2H), 2.02 (t, J = 12.7 Hz, 1H), 1.89–1.74 (m, 3H), 1.63 (dq, J = 15.3, 8.6, 7.8 Hz, 2H), 1.09 (s, 3H), 0.86 (d, J = 6.9 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 168.43, 143.56, 133.86, 131.97, 125.56, 123.07, 67.88, 47.37, 41.61, 39.02, 38.70, 36.82, 31.55, 30.43, 17.99, 15.33. HRMS (DART): [M+H]+calcd for [C20H24NO3]+m / z 326.1751, found 326.1754. IR (neat, ATR): νmax 3408 (br), 2956, 2928, 2857, 1767, 1709, 1376, 721 cm–1. Optical Rotation: [α]24 D = 19.50 (c 0.2, CHCl3)Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOThe alcohol 72 (80.0 mg, 0.220 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (5 mL). After heating under reflux for 6 h, the reaction mixture was concentrated in vacuo. DCM (10 mL) was added to the residue and the resulting suspension was filtered. The filtrate was concentrated and the residue purified through silica gel FCC (Rf = 0.43; 7 N NH3 in MeOH / MeOH / DCM, 1:1:10) to provide an off-white solid. DCM (2 mL) was added and the resulting suspension was filtered to remove the silica that had dissolved in eluent. The DCM solution was concentrated to afford 73 as an off-white solid (33.4 mg, 70% yield). 1H NMR (400 MHz, CDCl3) δ 5.31 (d, J = 1.6 Hz, 1H), 4.20 (ddt, J = 10.0, 6.3, 2.2 Hz, 1H), 2.95 (s, 1H), 2.29 (tdt, J = 14.1, 4.3, 2.1 Hz, 1H), 2.06 (ddd, J = 14.3, 4.2, 2.6 Hz, 1H), 1.97 (dt, J = 12.5, 2.9 Hz, 1H), 1.94–1.83 (m, 1H), 1.73 (ddt, J = 12.3, 6.4, 2.0 Hz, 1H), 1.60 (s, 2H), 1.48 (dqd, J = 13.6, 6.9, 2.2 Hz, 1H), 1.32 (td, J = 12.6, 9.9 Hz, 1H), 1.02 (dtd, J = 13.9, 11.9, 4.3 Hz, 1H), 0.94 (s, 3H), 0.87 (d, J = 6.9 Hz, 3H), 0.77 (t, J = 12.1 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 144.70, 124.98, 67.66, 49.49, 46.76, 39.22, 38.41, 38.01, 36.90, 31.37, 18.52, 15.39. HRMS (DART): [M+H]+calcd for [C12H22NO]+m / z 196.1696, found 196.1695. IR (neat, ATR): νmax 3304 (br), 2965, 2925, 2854, 1582, 1459, 1328, 1148, 1086, 1028 cm–1. Optical Rotation: [α]25 D = 39.00 (c 0.1, CH2Cl2).The indole 74 was synthesized following a modification of the procedure reported in the literature (81). A mixture of L-(+)-tartaric acid and DMU (30:70; 6.00 g) was heated at 90 °C to obtain a clear melt.4-Methoxyphenylhydrazine hydrochloride (140 mg, 0.800 mmol) was added to the melt. Once the hydrazine hydrochloride had dissolved, the melt was cooled to 70 °C. The ketone 32b (205 mg, 0.600 mmol) was dissolved in a minimum of DCM and added to the melt mixture at 70 °C. The mixture was stirred at 70 °C for 2 h, then cooled toAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO room temperature and treated with water (10 mL) and EtOAc (10 mL). The aqueous phase was extracted with EtOAc (2 × 10 mL). The organic phase was washed with brine (10 mL), dried (Na2SO4), and concentrated under reduced pressure. The residue was purified through silica gel FCC (Rf = 0.46; EtOAc / hexanes, 1:1) to give 74 as a yellow solid (145.4 mg, 55% yield).1H NMR (400 MHz, CD3CN) δ 8.77 (s, 1H), 7.76–7.63 (m, 4H), 7.23–7.17 (m, 1H), 6.95 (d, J = 2.5 Hz, 1H), 6.71 (dd, J = 8.7, 2.4 Hz, 1H), 4.60 (tt, J = 12.7, 4.9 Hz, 1H), 3.82 (s, 3H), 3.24 (dd, J = 16.2, 2.0 Hz, 1H), 3.04 (q, J = 6.9, 6.2 Hz, 1H), 2.84–2.67 (m, 1H), 2.54 (qd, J = 13.3, 4.8 Hz, 1H), 2.36 (d, J = 16.1 Hz, 1H), 2.16–1.98 (m, 2H), 1.96 (s, 1H), 1.67–1.54 (m, 2H), 1.42 (ddd, J = 13.6, 4.6, 2.1 Hz, 1H), 1.26 (d, J = 7.1 Hz, 3H), 0.97 (s, 3H). 13C NMR (100 MHz, CD3CN) δ 169.33, 154.73, 137.57, 134.89, 133.02, 132.64, 129.18, 123.54, 112.26, 111.35, 106.58, 100.68, 76.65, 56.20, 46.85, 38.32, 38.07, 34.60, 30.99, 30.65, 24.93, 22.22, 11.55. HRMS (DART): [M+H]+calcd for [C27H29N2O4]+m / z 440.2122, found 440.2109. IR (neat, ATR): νmax3537 (br), 3413 (br), 2936, 2851, 1702, 1482, 1467, 1396, 1374, 1216, 1145, 1083 cm–1. Optical Rotation: [α]25 D = 140.00 (c 0.1, CH2Cl2). M.p.: 154 °C (decomposition).The indole 74 (88.9 mg, 0.200 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (5 mL). After heating under reflux for 2 h under argon, the reaction mixture was concentrated in vacuo. DCM (10 mL) was added to the residue and the resulting suspension was filtered. The filtrate was concentrated and the residue purified through silica gel FCC (Rf= 0.18; 7 N NH3in MeOH / DCM, 1:10) to give the off-white solid. DCM (2 mL) was added and the resulting suspension was filtered to remove the silica that had dissolved in the eluent. The DCM solution was concentrated to afford 75 as an off-white solid (50.8 mg, 81% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CD3OD) δ 7.16 (d, J = 8.7 Hz, 1H), 6.85 (d, J = 2.5 Hz, 1H), 6.67 (dd, J = 8.7, 2.4 Hz, 1H), 3.79 (s, 3H), 3.20–2.98 (m, 3H), 2.28 (d, J = 15.6 Hz, 1H), 2.01 (td, J = 13.7, 4.2 Hz, 1H), 1.84–1.73 (m, 2H), 1.58 (qd, J = 13.1, 4.2 Hz, 1H), 1.43–1.31 (m, 4H), 1.12 (t, J = 12.6 Hz, 1H), 0.97 (s, 3H). 13C NMR (100 MHz, CD3OD) δ 154.80, 137.79, 133.58, 129.42, 112.21, 111.10, 106.37, 101.00, 77.19, 56.36, 47.03, 38.51, 38.45, 36.66, 34.98, 31.17, 30.94, 22.56, 11.69. HRMS (DART): [M+H]+calcd for [C19H27N2O2]+m / z 315.2067, found 315.2061. IR (neat, ATR): νmax 3386 (br), 2979, 2917, 2857, 1468, 1236, 1089, 926, 885 cm–1. Optical Rotation: [α]26 D = 62.00 (c 0.1, MeOH). M.p.: 144 °C (decomposition).Prepared following General procedure A using phthalimide (294 mg, 2.00 mmol, 1.0 equiv), copper(I) chloride (39.6 mg, 0.400 mmol, 20 mol %), 1,10-phenanthroline (72.1 mg, 0.400 mmol, 20 mol %), and MeCN (20 mL) to make Solution A and (–)-dihydrocarveol (771 mg, 5.00 mmol, 2.5 equiv) and MeCN (20 mL) to make Solution B. The crude product was purified through FCC to give 76 (Rf= 0.34; hexanes / Et2O, 1:3) as a white solid (315.8 mg, 61% yield) and 76-minor (Rf = 0.39; hexanes / Et2O, 1:3) as a white solid (104.9 mg, 20% yield).1H NMR (500 MHz, CDCl3) δ 7.81 (dt, J = 7.3, 3.6 Hz, 2H), 7.69 (dd, J = 5.4, 3.0 Hz, 2H), 4.18 (tt, J = 12.5, 3.9 Hz, 1H), 3.24 (td, J = 10.6, 4.3 Hz, 1H), 2.36–2.17 (m, 2H), 2.03 (dtd, J = 11.6, 4.0, 2.2 Hz, 1H), 1.82 (dq, J = 13.8, 3.5 Hz, 1H), 1.67 (ddt, J = 12.5, 6.3, 3.6 Hz, 1H), 1.49–1.39 (m, 1H), 1.16–1.08 (m, 1H), 1.06 (d, J = 6.4 Hz, 3H). 13C NMR (125 MHz, CDCl3) δ 168.26, 133.90, 131.92, 123.14, 75.13, 48.80, 39.17, 38.30, 31.44, 29.00, 18.01. HRMS (DART): [M+H]+calcd for [C15H18NO3]+m / z 260.1281, found 260.1281.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax3458 (br), 2929, 2873, 1772, 1708, 1466, 1397, 1389, 1376, 1335, 1105, 1056, 1043, 720 cm–1. Optical Rotation: [α]24 D = –3.50 (c 0.1, CHCl3). M.p.: 152–156 °C.1H NMR (400 MHz, CDCl3) δ 7.79 (td, J = 5.2, 2.1 Hz, 2H), 7.69 (td, J = 5.2, 2.1 Hz, 2H), 4.58 (tt, J = 12.6, 4.2 Hz, 1H), 4.04–3.91 (m, 1H), 2.65 (td, J = 13.4, 2.7 Hz, 1H), 2.39 (qd, J = 14.3, 13.5, 4.3 Hz, 1H), 2.06 (tt, J = 13.4, 4.5 Hz, 1H), 1.99–1.87 (m, 1H), 1.66 (d, J = 13.6 Hz, 1H), 1.57–1.42 (m, 2H), 1.10 (d, J = 7.3 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 168.53, 133.82, 132.04, 123.03, 72.12, 45.67, 33.56, 31.12, 25.45, 23.72, 16.40. HRMS (DART): [M+H]+calcd for [C15H18NO3]+m / z 260.1281, found 260.1281. IR (neat, ATR): νmax3487 (br), 2961, 2934, 2875, 1766, 1713, 1468, 1396, 1373, 1335, 1147, 1054, 1026, 967, 717 cm–1. Optical Rotation: [α]25 D = –7.67 (c 0.1, CHCl3). M.p.: 142–144 °C.The ammonium salt 77 was synthesized according to a literature procedure (80). The phthalimide 76 (130 mg, 0.500 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (5 mL). After the mixture had been stirred for 0.5 h at room temperature, 5% HCl (2 mL) was added and the mixture was stirred for an additional 12 h. The resulting suspension was filtered and then the filtrate was diluted with an equal amount of water, acidified (pH < 2), and washed with diethyl ether. The organic phase was discarded. The aqueous phase was basified with solid KOH (pH >10) and then extracted with diethyl ether (2 × 15 mL). The combined ethereal layers were washed with brine, dried (Na2SO4), and concentrated. The residue was dissolved in DCM (5 mL).4 M HCl in dioxane was added while cooling in an ice bath and then the mixture wasAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO stirred for 4 h at room temperature. Concentrating and washing with DCM provided 77 as a white crystal (73.2 mg, 88% yield). 1H NMR (400 MHz, CD3OD) δ 3.18–3.03 (m, 2H), 2.22 (dtd, J = 11.6, 4.0, 2.4 Hz, 1H), 1.94 (ddt, J = 12.9, 6.2, 3.5 Hz, 1H), 1.79 (dq, J = 13.9, 3.6 Hz, 1H), 1.41–1.21 (m, 3H), 1.15–1.02 (m, 1H), 1.00 (d, J = 6.4 Hz, 3H). 13C NMR (100 MHz, CD3OD) δ 72.67, 48.71, 38.95, 38.63, 29.72, 16.77. HRMS (DART): [M–Cl]+calcd for [C7H16NO]+m / z 130.1226, found 130.1226. IR (neat, ATR): νmax 3358 (br), 2952, 2876, 1637Optical Rotation: [α]25 D = –14.00(c 0.1, MeOH). M.p.: 186 °C (decomposition).Prepared following General procedure A using phthalimide (368 mg, 2.50 mmol, 1.0 equiv), copper(I) chloride (49.5 mg, 0.500 mmol, 20 mol %), 1,10-phenanthroline (90.1 mg, 0.500 mmol, 20 mol %), and MeCN (25 mL) to make Solution A. The alkene (–)-S36 (761 mg, 5.00 mmol, 2.0 equiv) was used for ozonolysis and MeCN (25 mL) to make Solution B. The crude product was purified through FCC to give (+)-36b-major (Rf= 0.55; EtOAc / hexanes, 1:2) as a white solid (360.8 mg, 56% yield) and (+)-36b-minor (Rf = 0.51; EtOAc / hexanes, 1:2) as a white solid (172.5 mg, 27 % yield).1H NMR (400 MHz, CDCl3) δ 7.86–7.75 (m, 2H), 7.74–7.62 (m, 2H), 4.46–4.30 (m, 1H), 3.17 (s, 1H), 2.67 (ddd, J = 14.5, 9.8, 2.3 Hz, 1H), 2.22 (ddt, J = 14.5, 5.2, 1.6 Hz, 1H), 2.18–1.97 (m, 2H), 1.92 (ddd, J = 15.2, 6.4, 3.8 Hz, 1H), 1.59–1.51 (m, 1H), 1.37 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.43, 133.91, 131.95, 123.11, 60.78, 57.08, 44.20, 28.24, 28.13, 25.01, 24.01. HRMS (DART): [M+H]+calcd for [C15H16NO3]+m / z 258.1125, found 258.1125. IR (neat, ATR): νmax2926, 2855, 1773, 1716, 1701, 1399, 1377, 1103, 878 cm–1.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Optical Rotation: [α]25 D = 3.50 (c 0.2, CHCl3). M.p.: 146–149 °C.1H NMR (400 MHz, CDCl3) δ 7.86–7.75 (m, 2H), 7.74–7.64 (m, 2H), 4.10 (dddd, J = 12.9, 11.7, 6.6, 3.0 Hz, 1H), 3.01 (d, J = 5.3 Hz, 1H), 2.63–2.37 (m, 2H), 2.22–1.99 (m, 2H), 1.87 (ddd, J = 14.8, 12.8, 4.9 Hz, 1H), 1.44–1.37 (m, 1H), 1.35 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.08, 133.90, 131.94, 123.14, 58.39, 56.98, 46.40, 30.42, 27.93, 23.43, 22.84. HRMS (DART): [M+H]+calcd for [C15H16NO3]+m / z 258.1125, found 258.1125. IR (neat, ATR): νmax2926, 2853, 1763, 1708, 1396, 1376, 1128, 1075, 718 cm–1. Optical Rotation: [α]25 D = 18.00 (c 0.2, CHCl3). M.p.: 187–190 °C.Deoxygenation was performed according to the literature (82). The epoxide (+)-36b- major (257 mg, 1.00 mmol), triphenyl phosphite (466 mg, 1.50 mmol), and rhenium(VII) oxide (2.40 mg, 0.5 mol %) were added in sequence to a 50-mL round-bottom flask in a glove box. The flask was capped with a rubber septum and removed from the glove box, followed by the addition of 10 mL of toluene. The mixture was stirred at 100 °C for 48 h and then cooled to room temperature. The mixture was concentrated and the residue purified through FCC to give 78 (Rf = 0.27; EtOAc / hexanes, 1:20) as a white solid (132.6 mg, 55% yield). The starting material epoxide (+)-36b-major (29.2 mg, 11% yield) was also recovered (62% yield b.r.s.).1H NMR (400 MHz, CDCl3) δ 7.85–7.77 (m, 2H), 7.72–7.65 (m, 2H), 5.37 (d, J = 4.5 Hz, 1H), 4.35 (dddd, J = 12.9, 11.3, 5.5, 3.2 Hz, 1H), 2.83 (dddt, J = 15.8, 8.8, 4.1, 2.2 Hz,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H), 2.55 (ddt, J = 18.3, 12.3, 5.9 Hz, 1H), 2.28–2.15 (m, 1H), 2.15–2.00 (m, 2H), 1.78 (dddt, J = 12.4, 5.0, 3.3, 1.7 Hz, 1H), 1.69 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 168.46, 133.79, 133.74, 132.10, 123.03, 119.23, 47.70, 30.52, 28.58, 26.47, 23.30. HRMS (DART): [M+H]+calcd for [C15H16NO2]+m / z 242.1176, found 242.1173. IR (neat, ATR): νmax 2958, 2915, 2852, 1699, 1612, 1464, 1394, 1380, 1107, 926, 876 cm–1. Optical Rotation: [α]25 D = –3.00 (c 0.1, CH2Cl2). M.p.: 147–150 °C.The alkene 78 (113 mg, 0.470 mmol) was dissolved in 0.3 M methanolic hydrazine hydrate (5 mL). The mixture was heated under reflux under argon for 3 h, then cooled to room temperature and diluted with DCM (20 mL). The suspension was filtered and the filtrate concentrated in vacuo at 0 °C. The residue was diluted with DCM (10 mL), the resulting suspension was filtered, and the filtrate concentrated in vacuo at 0 °C again. The residue was diluted with DCM (5 mL) and subjected to silica FCC (7 N NH3in MeOH / DCM, 1:30) to afford 79 (Rf = 0.24; 7 N NH3 in MeOH / DCM, 1:20) as a pale-yellow oil (44.5 mg, 85% yield). 1H NMR (400 MHz, CD2Cl2) δ 5.31–5.26 (m, 1H), 2.88 (dddd, J = 10.1, 8.5, 5.2, 3.2 Hz, 1H), 2.19 (ddtd, J = 16.6, 6.7, 3.5, 1.7 Hz, 1H), 2.10–1.92 (m, 2H), 1.81–1.65 (m, 2H), 1.65–1.59 (m, 3H), 1.43–1.31 (m, 3H). 13C NMR (100 MHz, CD2Cl2) δ 134.24, 119.77, 47.30, 36.03, 33.34, 29.78, 23.61. HRMS (DART): [M+H]+calcd for [C7H14N]+m / z 112.1121, found 112.1116. IR (neat, ATR): νmax3325 (br), 2930, 2835, 2857, 1572, 1448,1383, 1333, 1276 cm–1. Optical Rotation: [α]25 D = –50.33 (c 0.2, CH2Cl2). N-Methylation Reaction α-Methylstyrene (AMS) is an industrial by-product of the cumene–phenol process. The world market for AMS is 220k ton / year and is worth $120m. As mentioned in the main text, AMS is less expensive ($5.1 / mol) than other common methylation reagents. Other commercially available sources of Me+and / or Me• include CH(OMe)3($10.4 / mol), t- BuOOH ($8.9 / mol), Me2SO4 ($6.1 / mol), trimethyl phosphate ($12.6 / mol), MeOTsAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO ($26.3 / mol), di-tert-butylperoxide ($39.3 / mol), MeI ($42.6 / mol), di-cumylperoxide ($80.4 / mol), tert-butylperacetate ($33.6 / mol), PhI(OAc)2 ($331.6 / mol), and MesI(OAc)2 ($4,340.9 / mol). In a recent report, the Doyle group used trimethyl orthoformate (as the reaction solvent; 180 equiv) as the Me• source for the Ni / Ir-catalyzed methylation of (het)aryl chlorides (83). Methane would be the most atom-economical methylating agent, but its use would require a high-pressure photoreactor operating under at 50 bar (84). MeOH would be another atom-economical methylating agent, but not as a source of Me•, but rather HOCH2•, which eventually methylates aza-aromatics (85, 86). MeOH has also been used in the methylation of hydrocarbons in a flange reactor containing gallium nitride nanowires illuminated by a Xe lamp (87); here, MeOH is the source of methyl carbene. All of these examples, however, involve the formation of C–C bonds. One exception would be the use of MeOH in a precious metal–catalyzed hydrogen-borrowing strategy (hydrogen autotransfer) (88–92), but this process has not been used in the N-methylation of N-hetarenes. Case in point, the formaldehyde formed through the dehydration of MeOH undergoes C3 hydroxymethylation, eventually resulting in the 3-methylindole (93). In all cases, MeOH has been used as a (co)solvent (100–250 equiv). Recently, the MacMillan group reported an alcohol deoxygenative sp3–sp2cross-coupling enabled by metallaphotoredox catalysis where MeOH was used as a Me• precursor (94). A stoichiometric amount of NHC was, however, needed for activation. Acetic acid would be another atom-economical methylating agent, but the direct decarboxylation of an acid often favors the alkyl radical generated with adjacent stabilizing substituents. Methyl radical generation from acetic acid is often challenging (95) and, thus, excess amounts of acetic acid and oxidants are often employed (96). For example, 5 equiv of acetic acid and 10 equiv of AgNO3have been used in the methylation of acridine and 4-cyanopyridine (Minisci reaction) (97). In 2020, the Nocera group reported a photocatalyzed hydromethylation of active alkenes using acetic acid as a Me• precursor (95). This reaction is efficient and good yields were obtained when using only 3 equiv of acetic acid. Formation of an activated acetate ester intermediate is another strategy to engage acetic acid as a Me• precursor; for example, using PhI(OAc)2 (13) or N-acetyloxyphthalimide (98), which need stoichiometric activation reagents and an additional synthetic step. Notably, although the atom economy is low, the by-product from our protocol—methyl benzoate ($5.6 / mol)—is another value-added compound. It is relatively nonpolar and runs withAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO the solvent front of the eluent during FCC; therefore, it is easy to recover (85% yield). In an industrial setting, it would be readily separable from crystalline amino products. Note: The prices were checked from Thermo Scientific Chemicals on 02 / 06 / 2023. The price of MesI(OAc)2was checked from TCI.Prepared following General procedure A using S12 (61.0 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeCN (4 mL) to make Solution A. AMS (94.6 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 80 (Rf= 0.45; toluene / EtOAc, 2:1) as a colorless oil (56.2 mg, 84% yield). 1H NMR (400 MHz, CDCl3) δ 7.66 (d, J = 8.2 Hz, 1H), 7.43 (ddd, J = 7.9, 6.8, 1.0 Hz, 1H), 7.35 (d, J = 8.5 Hz, 1H), 7.19 (ddd, J = 7.8, 6.8, 0.8 Hz, 1H), 4.02 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 141.22, 132.38, 127.45, 121.11, 121.05, 119.74, 109.26, 35.79. HRMS (ESI-TOF): [M+H]+calcd for [C8H8ClN2]+m / z 167.0371, found 167.0378. IR (neat, ATR): νmax3061, 2936, 1618, 1498, 1470, 1383, 1366, 1231, 1165, 1121, 1030, 977, 742, 629, 595 cm–1.Prepared following General procedure A using theophylline (36.0 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeOH (20 mL) to make Solution A. AMS (47.3 mg, 0.400 mmol, 4.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give caffeine (Rf= 0.27; toluene / MeOH, 10:1) as a white solid (26.1 mg, 67% yield). 1H NMR (400 MHz, DMSO-d6) δ 7.97–7.91 (m, 1H), 3.85–3.78 (m, 3H), 3.34 (s, 3H), 3.15 (s, 3H).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 13C NMR (100 MHz, DMSO-d6) δ 154.95, 151.45, 148.52, 143.21, 107.01, 33.57, 29.80, 27.91. HRMS (DART): [M+H]+calcd for [C8H11N4O2]+m / z 195.0877, found 195.0878. IR (neat, ATR): νmax3111, 2959, 1697, 1651, 1599, 1548, 1485, 1455, 1429, 1402, 1359, 1285, 1237, 1025, 973, 744609, 482 cm–1. M.p.: 234–235 °C.Prepared following General procedure A using zidovudine (56.3 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (9.90 mg, 0.100 mmol, 50 mol %), 1,10-phenanthroline (18.0 mg, 0.100 mmol, 50 mol %), and MeOH (20 mL) to make Solution A. AMS (94.6 mg, 0.800 mmol, 4.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give 3-methylzidovudine (Rf = 0.24; EtOAc / hexanes, 2:1) as a colorless oil (43.4 mg, 77% yield). 1H NMR (500 MHz, CDCl3) δ 7.43 (d, J = 1.6 Hz, 1H), 6.06 (t, J = 6.4 Hz, 1H), 4.37 (dt, J = 7.5, 5.0 Hz, 1H), 4.00–3.89 (m, 2H), 3.84–3.73 (m, 1H), 3.30 (s, 3H), 2.84 (brs, 1H), 2.50 (dt, J = 13.7, 6.8 Hz, 1H), 2.38 (ddd, J = 13.9, 6.8, 5.2 Hz, 1H), 1.90 (s, 3H). 13C NMR (125 MHz, CDCl3) δ 163.63, 150.95, 134.68, 110.13, 87.29, 84.58, 61.90, 59.93, 37.45, 27.88, 13.28. HRMS (DART): [M+H]+calcd for [C11H16N5O4]+m / z 282.1197, found 282.1198. IR (neat, ATR): νmax3429 (br), 2932, 2102, 1697, 1666, 1629, 1474, 1296, 1257, 1101, 1060, 768 cm–1.Prepared following General procedure A using adenosine (107 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg,Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 0.0800 mmol, 20 mol %), and MeOH (20 mL) to make Solution A. AMS (94.6 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give m6A (Rf= 0.23; DCM / MeOH, 10:1) as a white solid (81.4 mg, 72 % yield). 1H NMR (500 MHz, DMSO-d6) δ 8.32 (s, 1H), 8.21 (s, 1H), 7.80 (s, 1H), 5.86 (d, J = 6.2 Hz, 1H), 5.41 (t, J = 6.9 Hz, 2H), 5.16 (d, J = 4.6 Hz, 1H), 4.59 (q, J = 6.0 Hz, 1H), 4.12 (q, J = 4.5 Hz, 1H), 3.94 (d, J = 3.0 Hz, 1H), 3.65 (dt, J = 11.9, 3.9 Hz, 1H), 3.53 (ddd, J = 11.7, 7.3, 3.5 Hz, 1H), 2.93 (brs, 3H). 13C NMR (125 MHz, DMSO-d6) δ 155.53, 152.88, 148.51, 140.11, 120.35, 88.37, 86.36, 73.93, 71.12, 62.14, 27.45 (br). HRMS (ESI-TOF): [M+H]+calcd for [C11H16N5O4]+m / z 282.1197, found 282.1198. IR (neat, ATR): νmax 3237 (br), 2931, 1633, 1376, 1334, 1228, 1093, 1084, 1055 cm–1. Optical Rotation: [α]24 D = –33.67 (c 0.1, MeOH). M.p.: 162 °C (decomposition).Prepared following General procedure A using adenosine (53.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeOH (10 mL) to make Solution A. AMS (118 mg, 1.00 mmol, 5.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give m6,6A (Rf= 0.35; DCM / MeOH, 10:1) as a white solid (58.2 mg, 99% yield). 1H NMR (500 MHz, CD3OD) δ 8.19 (s, 1H), 8.17 (s, 1H), 5.94 (d, J = 6.4 Hz, 1H), 4.73 (t, J = 5.8 Hz, 1H), 4.31 (dd, J = 4.7, 2.2 Hz, 1H), 4.16 (d, J = 2.1 Hz, 1H), 3.87 (dd, J = 12.5, 1.9 Hz, 1H), 3.73 (dd, J = 12.5, 2.1 Hz, 1H), 3.49 (brs, 6H). 13C NMR (125 MHz, CD3OD) δ 154.83, 151.24, 149.25, 138.78, 120.59, 89.80, 86.73, 73.82, 71.28, 62.11, 37.62 (br). HRMS (ESI-TOF): [M+H]+calcd for [C12H18N5O4]+m / z 296.1353, found 296.1361.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax3251 (br), 2926, 2870, 1598, 1568, 1487, 1426, 1341, 1300, 1276, 1221, 1122, 1082, 1038, 791, 697, 648 cm–1. Optical Rotation: [α]26 D = –29.50(c 0.2, MeOH) M.p.: 107–110 °C.Prepared following General procedure A using adenosine (53.4 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.0400 mmol, 20 mol %), and MeOH (10 mL) to make Solution A. D3-AMS (48.5 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give D3-m6A (Rf = 0.23; DCM / MeOH, 10:1) as a white solid (43.0 mg, 76% yield). 1H NMR (400 MHz, CD3OD) δ 8.20 (s, 1H), 8.18 (s, 1H), 5.92 (d, J = 6.5 Hz, 1H), 4.73 (dd, J = 6.5, 5.1 Hz, 1H), 4.30 (dd, J = 5.1, 2.5 Hz, 1H), 4.15 (q, J = 2.5 Hz, 1H), 3.86 (dd, J = 12.6, 2.5 Hz, 1H), 3.72 (dd, J = 12.5, 2.7 Hz, 1H), 3.03 (s, 5.3% × 3H). 13C NMR (125 MHz, CD3OD) δ 155.45, 152.06, 147.36, 140.03, 120.19, 89.86, 86.80, 74.04, 71.32, 62.11, 25.72 (br). HRMS (ESI-TOF): [M+H]+calcd for [C11H13D3N5O4]+m / z 285.1385, found 285.1387. IR (neat, ATR): νmax3201 (br), 2935, 1617, 1480, 1335, 1298, 1226, 1091, 1052, 983, 861, 813, 791, 755, 703, 641 cm–1. Optical Rotation: [α]24 D = –27.00 (c 0.1, MeOH) M.p.: 138 °C (decomposition).Prepared following General procedure A using deoxyadenosine (50.2 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.0400 mmol, 20 mol %), 1,10-phenanthrolineAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO (7.20 mg, 0.0400 mmol, 20 mol %), and MeOH (10 mL) to make Solution A. AMS (47.3 mg, 0.400 mmol, 2.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give m6dA (Rf= 0.24; DCM / MeOH, 10:1) as a white solid (41.3 mg, 78% yield). 1H NMR (500 MHz, CD3OD) δ 8.24 (s, 1H), 8.21 (s, 1H), 6.49–6.34 (m, 1H), 4.62– 4.52 (m, 1H), 4.12–4.01 (m, 1H), 3.84 (dd, J = 12.3, 2.5 Hz, 1H), 3.73 (dd, J = 12.3, 3.0 Hz, 1H), 3.09 (s, 3H), 2.80 (dt, J = 13.6, 6.0 Hz, 1H), 2.39 (ddd, J = 13.4, 5.8, 2.2 Hz, 1H). 13C NMR (125 MHz, CD3OD) δ 155.43, 152.05, 147.41, 139.60, 120.09, 88.51, 85.80, 71.70, 62.29, 40.18, 26.27. HRMS (ESI-TOF): [M+H]+calcd for [C11H16N5O3]+m / z 266.1248, found 266.1251. IR (neat, ATR): νmaxcm–1.3300 (br), 3097, 1632, 1622, 1381, 1319, 1246, 1082, 1071, 1027, 976, 929, 889, 851, 797, 654 cm–1. Optical Rotation: [α]24 D = –11.33 (c 0.1, MeOH) M.p.: 201–204 °C.Prepared following General procedure A using deoxyadenosine (97.3 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeOH (20 mL) to make Solution A. AMS (94.6 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give m4C (Rf= 0.14; DCM / MeOH, 2:1) as a white solid (71.4 mg, 69% yield). 1H NMR (500 MHz, CD3OD) δ 7.90 (d, J = 7.6 Hz, 1H), 5.84 (d, J = 3.2 Hz, 1H), 5.81 (d, J = 7.5 Hz, 1H), 4.16–4.09 (m, 2H), 4.00 (dt, J = 5.5, 3.0 Hz, 1H), 3.86 (dd, J = 12.3, 2.6 Hz, 1H), 3.73 (dd, J = 12.3, 3.2 Hz, 1H), 2.88 (s, 3H). 13C NMR (125 MHz, CD3OD) δ 164.59, 157.46, 139.91, 95.42, 90.87, 84.34, 74.68, 69.38, 60.62, 26.38. HRMS (ESI-TOF): [M+Na]+calcd for [C10H15N3NaO5]+m / z 280.0904, found 280.0905.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO IR (neat, ATR): νmax3163, 2927, 1633, 1617, 1539, 1500, 1401, 1291, 1107, 1090, 1055, 1020, 1004, 786, 779, 767 cm–1. Optical Rotation: [α]24 D = 20.00 (c 0.1, MeOH) M.p.: 213–214 °C.Prepared following General procedure A using deoxyadenosine (90.9 mg, 0.400 mmol, 1.0 equiv), copper(I) chloride (7.90 mg, 0.0800 mmol, 20 mol %), 1,10-phenanthroline (14.4 mg, 0.0800 mmol, 20 mol %), and MeOH (20 mL) to make Solution A. AMS (94.6 mg, 0.800 mmol, 2.0 equiv) was used for ozonolysis and MeCN (4 mL) to make Solution B. The crude product was purified through FCC to give m4dC (Rf = 0.45; DCM / MeOH, 2:1) as a white solid (71.9 mg, 75% yield). 1H NMR (400 MHz, CD3OD) δ 7.85 (d, J = 7.5 Hz, 1H), 6.24 (t, J = 6.6 Hz, 1H), 5.81 (d, J = 7.6 Hz, 1H), 4.33 (dt, J = 6.7, 3.6 Hz, 1H), 3.89 (q, J = 3.6 Hz, 1H), 3.75 (dd, J = 12.0, 3.3 Hz, 1H), 3.69 (dd, J = 12.0, 3.9 Hz, 1H), 2.86 (s, 3H), 2.30 (ddd, J = 13.5, 6.1, 3.7 Hz, 1H), 2.10 (dt, J = 13.5, 6.6 Hz, 1H). 13C NMR (100 MHz, CD3OD) δ 164.55, 157.22, 139.43, 95.57, 87.34, 85.98, 70.69, 61.43, 40.51, 26.37. HRMS (ESI-TOF): [M+Na]+calcd for [C10H15N3NaO4]+m / z 264.0955, found 264.0960. IR (neat, ATR): νmax 3266 (br), 3135, 1626, 1620, 1573, 1519, 1403, 1337, 1290, 1089, 1060, 1039, 1029, 954, 790, 776, 743, 664 cm–1. Optical Rotation: [α]24 D = 35.00 (c 0.1, MeOH) M.p.: 199–201 °C.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Preparation of m6,6A on 20-mmol-ScaleAn oven-dried 5-L round-bottom flask equipped with a magnetic stirrer bar was charged with adenosine (5.34 g, 20.0 mmol, 1.0 equiv), 1,10-phenanthroline (720 mg, 4.00 mmol, 20 mol %), HPLC-grade MeOH (1.85 L), and HPLC-grade MeCN (400 mL). The suspension was sparged with argon for 30 min to expel air and capped with a sleeve stopper. This mixture was stirred at room temperature for 20 min to form a suspension. The stirring was stopped and copper(I) chloride (396 mg, 4.0 mmol, 20 mol %) was added quickly. The mixture was sparged with argon for 30 min and stirred for 2 h. Another 250-mL round-bottom flask equipped with a magnetic stirrer bar was charged with AMS (11.8 g, 100 mmol, 5.0 equiv) and HPLC-grade MeOH (150 mL), then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution through a long needle until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 30 min to expel excess ozone and oxygen, and then the reaction mixture was warmed to room temperature. This MeOH solution of the hydroperoxide was added into the copper mixture via cannula and washed with additional MeOH (2 × 10 mL). The reaction vessel was stirred at room temperature for 24 h. Upon completion of the reaction (TLC), the mixture was concentrated to approximately 150 mL. The residue was transferred into a 500-mL round-bottom flask and diluted with DCM (200 mL). Silica gel (ca. 100 g) was added into the solution and the blue copper(II) salt absorbed onto it. The mixture was filtered through silica gel and washed with MeOH / DCM (1:2, v / v; 2 × 500 mL). The combined solutions were evaporated in vacuo and the residue was washed with DCM (3 × 30 mL) to afford a white solid. The DCM washings were combined and concentrated. This residue was washed with DCM (3 × 15 mL) to provide a small amount of white solid. The combined white solids were dried under high vacuum at 60 °C for 2 h to give m6,6A as a white solid (5.55 g, 94% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Synthesis of Terpene Nucleoside AnalogsPrepared following General procedure A using 2´,3´-O-isopropylideneadenosine (61.5 mg, 0.200 mmol, 1.0 equiv) copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10- phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (5 mL) to make Solution A. The alkene S32 (236 mg, 1.00 mmol, 5.0 equiv) was used for ozonolysis and MeCN (5 mL) to make Solution B. The crude product was purified through FCC to give 82 (Rf= 0.38; EtOAc) as a white solid (49.2 mg, 49% yield). 1H NMR (400 MHz, CD3OD) δ 8.22 (s, 1H), 8.18 (s, 1H), 6.09 (d, J = 3.6 Hz, 1H), 5.23 (dd, J = 6.0, 3.6 Hz, 1H), 5.00 (dd, J = 6.1, 2.2 Hz, 1H), 4.33 (q, J = 3.5 Hz, 2H), 3.76 (dd, J = 12.1, 3.4 Hz, 1H), 3.68 (dd, J = 12.1, 3.9 Hz, 1H), 2.92 (q, J = 6.6 Hz, 1H), 2.66 (td, J = 13.2, 12.5, 7.0 Hz, 1H), 2.27–2.09 (m, 2H), 2.09–1.99 (m, 1H), 1.98–1.90 (m, 1H), 1.83 (d, J = 12.8 Hz, 1H), 1.66–1.52(m, 4H), 1.46–1.31 (m, 5H), 1.23 (s, 3H), 1.18–1.09 (m, 1H), 0.96 (d, J = 6.7 Hz, 3H). 13C NMR (100 MHz, CD3OD) δ 212.05, 153.90, 152.25, 147.70, 139.85, 119.55, 113.82, 91.48, 86.62, 83.85, 81.54, 78.00, 62.18, 51.59, 45.87, 37.27, 37.16, 33.95, 31.19, 29.33, 26.87, 26.24, 24.17, 20.44, 5.65. HRMS (DART): [M+H]+calcd for [C25H36N5O6]+m / z 502.2660, found 502.2661. IR (neat, ATR): νmax 3368 (br) 2982, 2932, 2873, 1702, 1622, 1479, 1376, 1217, 1097, 1082, 1058, 851 cm–1. Optical Rotation: [α]23 D = –2.78 (c 0.3, CHCl3) M.p.: 146 °C (decomposition).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOPrepared following General procedure C using copper(I) chloride (5.90 mg, 0.0600 mmol, 30 mol %), 1,10-phenanthroline (10.8 mg, 0.0600 mmol, 30 mol %), and MeCN (4 mL) to make Solution C. (+)-Nootkatone (218 mg, 1.00 mmol, 5.0 equiv) was used for ozonolysis. 2´,3´-O-Isopropylideneadenosine (61.5 mg, 0.200 mmol, 1.0 equiv) and MeCN (9 mL) were added to make Suspension C. The crude product was purified through FCC to give 69 (Rf = 0.38; EtOAc) as a white solid (80.3 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.79 (s, 1H), 6.66 (brs, 1H), 6.03 (brs, 1H), 5.83 (d, J = 4.8 Hz, 1H), 5.80–5.73 (m, 1H), 5.17 (t, J = 5.3 Hz, 1H), 5.11–4.99 (m, 1H), 4.58 (brs, 1H), 4.51 (s, 1H), 3.94 (dd, J = 12.8, 1.3 Hz, 1H), 3.83–3.68 (m, 1H), 2.75–2.58 (m, 1H), 2.46–2.36 (m, 1H), 2.35–2.27 (m, 2H), 2.22 (d, J = 4.4 Hz, 1H), 2.00 (tt, J = 13.1, 6.0 Hz, 1H), 1.61 (s, 3H), 1.35 (s, 4H), 1.29–1.11 (m, 5H), 0.93 (d, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 199.24, 174.91, 168.23, 154.32, 152.85, 139.62, 125.18, 113.97, 94.30, 86.07, 83.00, 81.72, 63.39, 45.67, 44.71, 41.69, 40.42, 39.73, 32.81, 31.64, 27.66, 25.26, 21.07, 16.99, 14.91. HRMS (DART): [M+H]+calcd for [C25H34N5O5]+m / z 484.2554, found 484.2554. IR (neat, ATR): νmax3314 (br) 2976, 2940, 1661, 1619, 1477, 1375, 1295, 1217, 1112, 1084, 851, 758 cm–1. Optical Rotation: [α]25 D = 4.36 (c 0.2, CHCl3) M.p.: 77 °C (decomposition).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Prepared following General procedure C using copper(I) chloride (3.00 mg, 0.0300 mmol, 30 mol %), 1,10-phenanthroline (5.40 mg, 0.0300 mmol, 30 mol %), and MeCN (2 mL) to make Solution C. The alkene S44 (139 mg, 0.500 mmol, 5.0 equiv) was used for ozonolysis. 2´,3´-O-Isopropylideneadenosine (30.7 mg, 0.100 mmol, 1.0 equiv) and MeCN (5 mL) were used to make Suspension C. The crude product was purified through FCC to give 84 (Rf = 0.27; hexanes / EtOAc, 1:1) as a white solid (48.6 mg, 83% yield). 1H NMR (400 MHz, CDCl3) δ 8.30 (s, 1H), 7.74 (s, 1H), 6.82 (brs, 1H), 6.22 (s, 1H), 5.81 (d, J = 4.9 Hz, 1H), 5.18 (t, J = 5.4 Hz, 1H), 5.09 (d, J = 5.8 Hz, 1H), 4.51 (s, 1H), 4.00– 3.86 (m, 1H), 3.76 (d, J = 12.8 Hz, 1H), 3.64 (d, J = 27.9 Hz, 2H), 2.88–2.69 (m, 1H), 2.05 (s, 3H), 1.80–1.51 (m, 10H), 1.49 (s, 3H), 1.46–1.38 (m, 1H), 1.35 (s, 4H), 1.25 (q, J = 15.0, 13.6 Hz, 1H), 1.12 (td, J = 13.3, 3.8 Hz, 1H), 1.05–0.92 (m, 2H), 0.84 (s, 3H), 0.83 (s, 3H), 0.76 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 170.30, 155.27, 152.82, 147.12, 139.30, 121.34, 113.89, 94.40, 87.49, 86.01, 82.96, 81.76, 63.47, 56.22, 55.56, 42.36, 41.76, 39.61, 39.30, 38.92, 33.29, 33.09, 27.69, 25.37, 25.26, 23.09, 21.41, 20.02, 19.92, 18.24, 15.62. HRMS (DART): [M–OAc]+calcd for [C29H44N5O4]+m / z 526.3388, found 526.3388. IR (neat, ATR): νmax3243 (br), 2991, 2939, 2871, 1723, 1622, 1476, 1387, 1297, 1252, 1114, 1081, 851, 754 cm–1. Optical Rotation: [α]25 D = –23.83 (c 0.2, CHCl3) M.p.: 78 °C (decomposition).Prepared following General procedure A using 2´,3´-O-isopropylideneadenosine (61.5 mg, 0.200 mmol, 1.0 equiv), copper(I) chloride (4.00 mg, 0.400 mmol, 20 mol %), 1,10-phenanthroline (7.20 mg, 0.200 mmol, 50 mol %), and MeOH (5 mL) to make Solution A. (–)-Isopulegol (92.5 mg, 0.600 mmol, 3.0 equiv) was used for ozonolysis and MeCN (2 mL) to make Solution B. The crude product was purified through FCC to give 85 (Rf = 0.26; EtOAc / MeOH, 20:1) as a white solid (67.1 mg, 80% yield).Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 1H NMR (400 MHz, CDCl3) δ 8.05 (s, 1H), 7.69 (s, 1H), 7.41 (brs, 1H), 6.42 (brs, 1H), 5.74 (d, J = 5.0 Hz, 1H), 5.19 (t, J = 5.4 Hz, 1H), 5.11 (d, J = 5.9 Hz, 1H), 3.98 (brs, 1H), 3.87 (d, J = 12.5 Hz, 1H), 3.77–3.55 (m, 2H), 2.23–2.11 (m, 1H), 2.10–1.96 (m, 1H), 1.72–1.61 (m, 4H), 1.60–1.50 (m, 1H), 1.46 (s, 3H), 1.38–1.26 (m, 1H), 1.26–1.07 (m, 2H), 0.98 (d, J = 6.5 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 154.59, 152.44, 146.26, 138.89, 120.07, 114.08, 94.61, 86.25, 82.78, 81.66, 74.00, 63.31, 56.06, 44.33, 33.14, 31.63, 31.16, 27.83, 25.25, 21.93. HRMS (ESI-TOF): [M+H]+calcd for [C20H30N5O5]+m / z 420.2241, found 420.2242. IR (neat, ATR): νmax 3321 (br), 2926, 2855, 1623, 1588, 1479, 1376, 1337, 1298, 1216, 1113, 1083, 851, 761 cm–1. Optical Rotation: [α]25 D = –30.00 (c 0.1, CHCl3) M.p.: 64 °C (decomposition). Synthesis of Cu Complexes The copper complexes 87-89 were synthesized according to previously reported procedures. Scheme S17. Copper complexes preparedThe complex 86 was prepared using the following procedure.The copper(I) complex [(Phen)Cu(Phth)] (86) was synthesized using a modification of a procedure reported in the literature (51). An oven-dried 50-mL round-bottom flask equipped with a magnetic stirrer bar was treated with CuCl (119 mg, 1.20 mmol, 1.04 equiv) and potassium tert-butoxide (135 mg, 1.20 mmol, 1.04 equiv). The flask was purged with argon three times and then THF (10 mL) was added. The mixture was stirred at room temperature for 6 h and then 1,10-phenanthroline (207 mg, 1.15 mmol, 1.0 equiv) was added quickly. The flaskAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO was degassed and refilled with argon three times and then stirred for 20 min. Phthalimide (176 mg, 1.20 mmol, 1.04 equiv) was added into the mixture quickly. The flask was degassed and refilled with argon three times and then stirred for 20 min. The mixture was concentrated in vacuo and refilled with argon to afford a solid; the flask was capped with a sleeve stopper. This solid was dissolved in a mixture of DMSO (4 mL) and THF (1 mL), added via syringe, and then Et2O (15 mL) was added slowly and carefully via syringe to afford a bilayer solution. Red crystals had formed after standing for 2 days. The liquid phase was removed by syringe and the solid was washed with THF (5 × 1.5 mL, using syringe for adding and removing) under an argon atmosphere. The solid was dried in vacuo. The crude red solid was washed with DI water (3 × 3 mL) under an argon atmosphere and then benzene (10 mL) was added. The benzene was evaporated in vacuo to remove water; this procedure was repeated four times to give [(Phen)Cu(Phth)] as red crystals (162.1 mg, 35% yield). 1H NMR (400 MHz, DMSO-d6) δ 9.07 (br s, 2H), 8.79 (d, J = 7.3 Hz, 2H), 8.25 (br s, 2H), 8.02 (s, 2H), 7.68–7.47 (m, 4H), matching the literature data (45). Control Experiments General procedure An oven-dried 8-mL Schlenk tube equipped with a magnetic stirrer bar was charged with phthalimide (29.4 mg, 0.200 mmol, 1.0 equiv) and a copper catalyst (0.0400 mmol for total amount of copper, 20 mol %) [and tetraethylaminonium chloride (TEACl) (0.1 mmol, 50 mol %) when appropriate]. The tube was purged with argon three times before dry MeCN (2 mL) was added. [Note: When complex 87 was used, dry MeOH (0.4 mL) and dry MeCN (1.6 mL) was used.] This mixture was stirred at room temperature for 10 min to make Suspension A. Another 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with (–)-dihydrocarveol (154 mg, 1.00 mmol) and MeOH (20 mL, 0.05 M) and cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material (as indicated by TLC and / or a bluish color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved in benzene (10 mL) followed by evaporation in vacuo to remove adventitious water. The residue was dissolved in MeCN to form a 0.2 M solution of the hydroperoxide. A portionAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO (2.0 mL) of this hydroperoxide solution was transferred into Suspension A in the Schlenk tube via syringe. The reaction vessel was stirred at room temperature for 1 h, followed by adding 1- chloro-2,4-dinitrobenzene (40.5 mg, 0.200 mmol, 1.0 equiv) as an internal standard. The mixture was concentrated in vacuo. The residue was passed through a short plug of silica gel to remove copper salts prior to concentration in vacuo. The crude materials were analyzed using NMR spectroscopy. Table 7. Comparison of different Cu complexesentry catalyst and salt yield (%) d.r. 1 Phen (20 mol %) + CuCl (20 mol %) 90 2.9:1.0 2 [(Phen)Cu(Phth)] (86) (20 mol %) 45 1.8:1.0 3*[(Phen)Cu(Phth)2] (87) (20 mol %) 44 1.4:1.0 4 [(Phen)2Cu][CuCl2] (88) (10 mol %) 87 2.8:1.0 5 [(Phen)2Cu]BF4 (89) (20 mol %) <6 N.D. 6 CuCl (20 mol %) + TEACl (50 mol %) <5 N.D. [(Phen)2Cu]BF4 (10 mol %) + CuCl (10 7 72 3.0:1.0 mol %) + TEACl (50 mol %) [(Phen)2Cu]BF4(89) (20 mol %) + TEACl 8 74 2.9:1.0 (50 mol %) Phen (20 mol %) + CuCl (20 mol %) + 9 75 3.2:1.0 TEACl (50 mol %) Phen (20 mol %) + CuCl (20 mol %) + 10 72 2.9:1.0 TBABF4 (50 mol %) * MeOH / MeCN (1:9, v / v) was used as the solvent because this complex did not dissolve in MeCNAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO Summary of Table 7: In attempts to directly probe the nature of the reactive copper species, a series of copper complexes were prepared (Fig. S17). To compare the performance of each putative copper species, they were employed in the aminodealkenylation between (–)- dihydrocarveol and phthalimide. When the prototypical mixture of 1:1 CuCl and phenanthroline were replaced by neutral copper imidate complexes [(Phen)Cu(phth)] (86) and [(Phen)Cu(phth)2] (87), which had been proposed previously as catalytic intermediates (15, 17, 51), both the product yields (45 and 44%, respectively) and diastereoisomeric ratios (d.r.) (1.8:1.0 and 1.4:1.0, respectively) deviated significantly from those of the standard reaction (90% NMR yield, 2.9:1.0 d.r.) (entries 1–3). Using the ion pair [(Phen)2Cu]+[CuCl2]–(88) directly afforded a reaction similar to that of the prototypical aminodealkenylation (87% yield, 2.8:1.0 d.r.) (entry 4), indicating that the ion pair might be the active catalytic species. Reactions employing either [(Phen)2Cu]+(89) or [CuCl2]–(CuCl + Et4NCl) were extremely sluggish (entries 5 and 6), while the combination of independently prepared [(Phen)2Cu]+and [CuCl2]–afforded a reaction similar to that of the parent reaction (entries 7–10) but with slightly diminished yield. UV–Vis Spectroscopy The absorbance of the CuCl and Phen mixture (trail A) almost overlaps with the absorbance of the complex 88 (trail B). This observation indicates that a 1:1 mixture of CuCl and Phen in MeCN forms the ion pair complex 88 predominantly. All of the trails have the same fingerprint absorbances at 324, 337, and 442 nm, which are the absorbances of [(Phen)2Cu]+, although trail C does not overlap perfectly with trails A and B. It was proposed that the shape and size of the counter anion (CuCl2–: linear and small; BF4–: tetrahedral and bulky) impacts the interactions between the cations and anions, particularly for these tight ion pairs. As a result, the absorbances of [(Phen)2Cu]+are slightly different. Tetraethylammonium chloride (TEACl) barely has any absorbances in the range from 250 to 600 nm (trail G). The absorbance of phthalimide (trail F) overlaps with the absorbance of a TEACl and phthalimide mixture (trail D), indicating that no interactions occurred between TEACl and phthalimide, and that the absorbance of the mixture was contributed solely by phthalimide. In contrast, a new peak at 295 nm appeared for the mixture of CuCl and TEACl (trail B), when compared with those of CuCl (trail E) and TEACl (trail G) individually. We believe that this new signal indicates that chloride coordinated with CuCl to form CuCl2–. The signal in the mixture of CuCl and phthalimide (trail C) exhibited a red-shift when comparedAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO with that of phthalimide (trail F), indicative of chelation between CuCl and phthalimide. For the mixture of CuCl, phthalimide, and TEACl (trail A), the red-shift was observed and a new peak appeared at 410 nm that must have been caused by the complex formed between CuCl2–and phthalimide. Example 2: Kinetics Studies General considerations and procedures for the ReactIR reaction setup During the reaction between the peroxide and the amine, the copper catalyst participates in both the C–C scission and C–N coupling events. To gain insight into the kinetic behavior of different copper species in these two steps, the formation of both methyl acetate (MeOAc) and the coupling product were monitored as proxies for the C–C scission and the C–N coupling events, respectively. Initially, the amination between the peroxide S32- peroxide and 3-chloroindazole was considered because in a previous study it was demonstrated that S32-peroxide could be generated quantitatively and was relatively stable (eq.1) (29). While MeOAc displays well-resolved strong absorbances at 1250 and 1740 cm–1, the strong carbonyl absorbance of the coupling product 32a at 1710 cm–1is identical to that of S32-peroxide and this intensity remained constant during the reaction. The product 32a does not have any other well-resolved or strong peaks to follow. With anticipation of a change in its carbonyl absorbance, phthalimide was adopted instead (eq.2). Interestingly, the phthalimide carbonyl absorbance changed from 1740 to 1710 cm–1, the latter overlapping with the carbonyl signals of S32-peroxid and 32b; the intensity of the peak at 1710 cm–1increased, however, in proportion to the formation of 32b because the intensities of the carbonyl signals of both S32-peroxid and 32b were almost identical. The carbonyl absorptions of MeOAc and phthalimide overlapped (1740 cm–1), so the peaks at 1116 and 1300 cm–1were used to monitor the consumption of S32-peroxide and phthalimide, respectively. The ReactIR data were analyzed using iC IR 7.1 software. Variable time normalization analysis (VTNA) was employed for kinetic analysis. When the exponent was equal to 0, the VTNA analysis diagram represented the reaction profile.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOAn oven-dried 25-mL three-neck flask equipped with a magnetic stirrer bar was capped with a rubber septum on the left neck. The ReactIR probe was equipped on the middle neck. The right neck was connected to the Schlenk line. The flask was purged with argon three times. Freshly prepared solutions of phthalimide, phenanthroline, copper, and peroxide were added into the three-neck flask sequentially via syringe. For the exact procedures for the preparation of solutions, see each section. Note: The reaction vessel should be sealed carefully because the copper(I) species are highly O2-sensitive. The juncture between the probe and probe adapter was sealed with Teflon tape. The bottom part of the stopper and the probe adapter were twined by Teflon tape prior to being capped onto the flask. Parafilm was used to seal the outside of the juncture. The right neck was sealed with high-vacuum grease. MeCN was freshly distilled, followed by three freeze / pump / thaw deoxygenation cycles prior to use. All of the materials were dissolved in deoxygenated MeCN and should be used as a solution. The junctures between the syringes and needles were sealed with Parafilm and the syringes and needles were purged with argon three times prior to use. To prevent the peroxide from slowly decomposing at room temperature (actually, it was found to be stable in MeCN at room temperature for a few hours), once made, the peroxide solution was kept at –78 °C and warmed to room temperature in a water bath prior to use. Determination of the reaction order of (CuCl + Phen) catalystAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO Preparation of the solutions Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Copper(I) chloride solution (0.015 M): A 50-mL round-bottom flask was charged with copper(I) chloride (29.7 mg, 0.300 mmol). The flask was capped with a Telfon tape– twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Phenanthroline solution (0.015 M): A 50-mL round-bottom flask was charged with phenanthroline (54.1 mg, 0.300 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid was dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (usually ca.4.2 mL) was added to give a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOThe amination between S32-peroxide and phthalimide using 20 mol % of CuCl and Phen was rapid and complete within 2 min, even at 0 °C; therefore, we could not collect a sufficient number of data points. In addition, it is generally suggested to use less than 10 mol % of a catalyst for kinetic studies. Consequently, 2.0–8.0 mol % of (CuCl + Phen) catalyst was used for the kinetic measurements. The reaction using 4 mol % of catalyst was complete within approximately 10 min, an optimal period for operation. As a result, 4 mol % of catalyst was used for determination of the reaction orders of peroxide and phthalimide (Sections 8.3 and 8.4). The kinetic studies of [CuCl2]–and [(Phen)2Cu]+were based on, and varied from, the 4 mol % Cu(I) loading conditions. The rates of 32b and MeOAc generation both decreased when the concentration of the catalyst was decreased from 8 to 2 mol %. The reaction traces did not overlap for both the first order and second order for 32b and MeOAc. It was found that orders of 1.3 for the generation of both 32b and MeOAc afforded the best overlap. This unusual 1.3-order-dependence on the (CuCl + Phen) catalyst for both C–C scission (MeOAc generation) and C–N coupling (32b generation) indicates bimolecular catalysis. Determination of the reaction order of phthalimidePreparation of the solutions:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Copper(I) chloride solution (0.015 M): A 50-mL round-bottom flask was charged with copper(I) chloride (29.7 mg, 0.300 mmol). The flask was capped with a Telfon tape– twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Phenanthroline solution (0.015 M): A 50-mL round-bottom flask was charged with phenanthroline (54.1 mg, 0.3 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then it was cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by evaporation in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (usually ca.4.2 mL) was added to give a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOA lower amount of peroxide led to a lower yield and shorter reaction time. To obtain a significant product peak intensity and sufficient data points, a half amount of phthalimide [0.075 mmol, compared with the standard condition (0.15 mmol)] was selected as the lowest concentration. Consequently, 0.075, 0.10, 0.125, 0.15, and 0.19 mmol of phthalimide were used to determine the reaction order. It was found that the rates of 32b generation decreased slightly upon decreasing the concentration of phthalimide. The traces of 32b generation overlapped the best when applying an order of 0.3 on phthalimide. Other reaction orders, including 0.5 and 1, did not afford such a good overlap. In contrast, the rates of MeOAc generation were almost identical when using different concentrations of phthalimide. Other reaction orders did not afford such a good overlap. Therefore, the generation of 32b was 0.3-order (pseudo-zero-order)–dependent on phthalimide. The generation of MeOAc was zero-order-dependent on phthalimide. 8.4 Determination of the reaction order of peroxide (alkene)Preparation of the solutions:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Copper(I) chloride solution (0.015 M): A 50-mL round-bottom flask was charged with copper(I) chloride (29.7 mg, 0.300 mmol). The flask was capped with a Telfon tape– twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Phenanthroline solution (0.015 M): A 50-mL round-bottom flask was charged with phenanthroline (54.1 mg, 0.300 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (330 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (usually about 4.2 mL) was added to give a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOA lower amount of peroxide led to a lower yield and shorter reaction time. To obtain a significant product peak intensity and sufficient data points, we selected a 60% amount of peroxide [0.18 mmol, compared with the standard condition (0.30 mmol)] as the lowest concentration. Consequently, we used 0.18, 0.21, 0.30, 0.36, and 0.42 mmol of phthalimide to determine the reaction order. It was found that the rates of generation of 32b and MeOAc both decreased slightly upon decreasing the concentration of peroxide. The traces for 32b and MeOAc generation both overlapped best when applying an order of 0.3. Other reaction orders, including 0.5 and 1, did not afford such a good fit. Therefore, the generations of 32b and MeOAc were both 0.3-order (pseudo-zero-order)–dependent on peroxide. Determination of the reaction order of [(Phen)2Cu]BF4Preparation of the solutions: Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argonAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Et4NCl solution (0.0075 M): A 50-mL round-bottom flask was charged with Et4NCl (37.3 mg, 0.225 mmol) in a glove box. The flask was capped with a Telfon tape–twined stopper and then removed from the glove box, followed by sealing with Parafilm wrapping around the joints. Degassed MeCN (30 mL) was then added. The flask was shaken gently until the entire white solid had dissolved. [Copper(I) chloride + Et4NCl] solution (0.0075 M): A 50-mL round-bottom flask was charged with copper(I) chloride (14.9 mg, 0.15 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before Et4NCl solution (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. [(Phen)2Cu]BF4 solutions: Solution A (3.75 mM): A 50-mL round-bottom flask was charged with [(Phen)2Cu]BF4(19.2 mg, 0.0375 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (10 mL) was added. The flask was shaken gently until the entire dark- red solid had dissolved. Solution B (0.375 mM): A 25-mL round-bottom flask was capped with a Telfon tape– twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before Solution A (1 mL) and degassed MeCN (9 mL) were added to afford Solution B. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then it was cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH was evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping aroundAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO the joints. The flask was purged with argon three times before degassed MeCN (usually ca.4.2 mL) was added to give a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Because control experiments suggested cooperative catalysis between [(Phen)2Cu]+and [CuCl2]–and the reaction displayed a 1.3-order-dependence on the (CuCl + Phen) catalyst, the roles and kinetics of [(Phen)2Cu]+and [CuCl2]–were studied separately. For the preliminary kinetic study of [(Phen)2Cu]BF4, concentrations ranging from 0.5 to 4 mol % were chosen. It was found, firstly, when using 4 mol % of [(Phen)2Cu]+(the concentration of [(Phen)2Cu]+was higher than that of [CuCl2]–), the rates of 32b and MeOAc generation both decreased significantly. It was posited that Phen could dissociate from the [(Phen)2Cu]2+complex and coordinate to [CuCl2L], significantly decreasing the concentration of [CuCl2L] and, as the consequence, slowing down the peroxide decomposition. This observation also fits with the kinetic study of phenanthroline. Secondly, the reaction traces for 32b generation overlapped best when applying a zero order. In contrast, the rate of MeOAc generation decreased slightly upon increasing the concentration of [(Phen)2Cu]BF4 from 0.5 to 2.0 mol %. It was surmised that this rate decrease was also due to Phen dissociation from [(Phen)2Cu]2+. The reaction traces overlapped best when applying a –0.3 order. Therefore, the generation of 32b was zero-order-Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO dependent on [(Phen)2Cu]BF4in the range from 0.5 to 2 mol % and the generation of MeOAc was –0.3-order (pseudo-zero-order)–dependent on [(Phen)2Cu]BF4 in the range from 0.5 to 2 mol %. Previous control experiments indicated that <5% of 32b was obtained when using CuCl and TEACl alone as the catalyst (Table 6). In fact, a mere 0.5 mol % of [(Phen)2Cu]BF4 produced a product yield of approximately 50%. Therefore, it was suspected that experiments using 0.5–2.0 mol % [(Phen)2Cu]BF4might exhibit saturation kinetics. Consequently, additional kinetic measurements were conducted using lower concentrations (0–0.5 mol %) of [(Phen)2Cu]BF4. Indeed, both the rate and yield of 32b formation decreased upon decreasing the amount of [(Phen)2Cu]BF4(Fig. S30, top left). The traces overlapped the best when applying an almost first order (0.8 or 0.9 might have been the best). The rate and yield of MeOAc formation were not affected by the concentration of [(Phen)2Cu]BF4. In particular, MeOAc was generated at the same rate even in the absence of [(Phen)2Cu]BF4. The traces overlapped the best when applying a zero order. In all, the generation of 32b was first-order-dependent on [(Phen)2Cu]BF4in the range from 0.1 to 0.5 mol %. The generation of MeOAc was zero-order- dependent on [(Phen)2Cu]BF4in the same range. Determination of the reaction order of (CuCl + Et4NCl) (1) [(Phen)2Cu]BF42.0 mol %, (CuCl + Et4NCl) from 2.0 to 4.0 mol %Preparation of the solutions: Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Et4NCl solution (0.0075 M): A 50-mL round-bottom flask was charged with Et4NCl (37.3 mg, 0.225 mmol) in glove box. The flask was capped with a Telfon tape–twined stopper, removed from the glove box, and sealed with Parafilm wrapping around the joints. DegassedAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. (Copper(I) chloride + Et4NCl) solution (0.0075 M): A 50-mL round-bottom flask was charged with copper(I) chloride (14.9 mg, 0.150 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before Et4NCl solution (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. [(Phen)2Cu]BF4 solution (3.75 mM): A 50-mL round-bottom flask was charged with [(Phen)2Cu]BF4 (19.2 mg, 0.0375 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (10 mL) was added. The flask was shaken gently until the entire dark-red solid had dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then it was cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (usually ca.4.2 mL) was added to make a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO[(Phen)2Cu]BF40.5 mol %, (CuCl + Et4NCl) from 1.0 to 2.0 mol %Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO After obtaining the kinetic data for [(Phen)2Cu]+, a kinetic study was conducted for [CuCl2]–. A 1:1 mixture of (CuCl + Et4NCl) was used to mimic a [CuCl2]–species. In the preliminary kinetic study of (CuCl + Et4NCl), concentrations ranging from 2.0 to 4.0 mol % were chosen in the presence of 2.0 mol % [(Phen)2Cu]BF4because the kinetics would change significantly if the concentration of [(Phen)2Cu]BF4 were higher than that of (CuCl + Et4NCl). The rates of 32b and MeOAc generation both became slow upon decreasing the concentration of (CuCl + Et4NCl) from 4.0 to 2.0 mol % . The 32b generation traces overlapped the best when applying an order of 1.3. The MeOAc generation traces overlapped similarly when applying an order of either 1 or 1.3. Each chart was compared and it was found that the trace for 2.0 mol % was slightly above all of the others. This trace was obtained from the set of earlier experiments. It was reasoned that the concentration of each solution made in this experiment might have been slightly different, so the 2.0 mol % was removed and a line graph instead of a scatter plot was generated. The MeOAc generation traces overlapped best when applying an order of 1.3. Thus, the rate of 32b and MeOAc generation were both 1.3-order- dependent on (CuCl + Et4NCl) when [(Phen)2Cu]+exhibited saturation kinetics (from 0.5 to 2.0 mol %). Because the kinetic behavior of [(Phen)2Cu]+was roughly divided into two parts (Section 8.5), next kinetic experiments were set up for [CuCl2]–species in the first-order region of [(Phen)2Cu]+(0.1 to 0.5 mol %). The concentration of [(Phen)2Cu]BF4 was selected to be 0.5 mol % because a further decrease in its concentration led to a low yield of 32b and a low absorbance. The rates of 32b and MeOAc generation both decreased dramatically upon decreasing the concentration of (CuCl + Et4NCl) from 2 to 1 mol %. The traces of 32b and MeOAc generation both overlapped best when applying a second order. Therefore, the rate of 32b and MeOAc generation were both second-order-dependent on (CuCl + Et4NCl) in the presence of a limited amount of [(Phen)2Cu]+, at which point it exhibits first-order kinetics for the C–N coupling step (from 0.1 to 0.5 mol %). Determination of the reaction order of phenanthrolinePreparation of the solutions:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Copper(I) chloride solution (0.015 M): A 50-mL round-bottom flask was charged with copper(I) chloride (29.7 mg, 0.300 mmol). The flask was capped with a Telfon tape– twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Phenanthroline solution (0.0075 M): A 50-mL round-bottom flask was charged with phenanthroline (27.1 mg, 0.150 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (20 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then it was cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step was repeated one more time. The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (usually ca.4.2 mL) was added to make a solution having a total volume of 4.5 mL. The phthalimide solution, phenanthroline solution, degassed MeCN, CuCl solution, and peroxide solution were added into a three-neck round-bottom flask sequentially. Volumes are indicated in the Table below.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOThe kinetics of phenanthroline were also studied as supplementary kinetic experiments. The idea was that a ratio of Phen:CuCl of less than 1:1 might generate a lower amount of [CuCl2]–, and the resulting excess CuCl could react with [CuCl2]–to form a cluster [CuxCly]x–y. Indeed, when using 4 mol % of CuCl, although the yield of the coupling product 32b decreased upon decreasing the amount of phenanthroline from 4.0 to 2.0 mol %, the rates of 32b formation remained similar. VTNA analysis revealed the best fit when applying an order of zero (Fig. S36). The MeOAc generation traces also overlapped the best when applying an order of zero (Fig. S37). Therefore, the rates of 32b and MeOAc generation were both zero-order-dependent on phenanthroline (from 2.0 to 4.0 mol %). Because a dramatic decrease in the reaction rate was observed when the concentration of [(Phen)2Cu]+was higher than that of [CuCl2]–, the reactions were also monitored under conditions in which a greater mole-percentage of phenanthroline (to CuCl) was present. Indeed, it was found that the rates of 32b and MeOAc generation both decreased dramatically when the amount of Phen ranged from 4.0 to 8.0 mol % in the presence of 4.0 mol % of CuCl, although the overall yields remained almost identical. The trails of 32b and MeOAc generation overlapped the best when applying orders of –5 and –4.6, respectively. It was suspected that an error might have occurred during the experiment performed using 5 mol % of Phen, because its trace deviated from the others. This trace was removed and it was found that the other traces fit well. Therefore, the rates of 32b and MeOAc generationAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO displayed –5- and –4.6-order-dependence on Phen, respectively (from 4.0 to 8.0 mol %) in the presence of 4.0 mol % of CuCl. Effect of chloridePreparation of the solutions: Phthalimide solution (0.05 M): A 50-mL round-bottom flask was charged with phthalimide (221 mg, 1.50 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (30 mL) was added. The flask was shaken gently until the entire white solid had dissolved. Et4NCl solution (0.075 M): A 50-mL round-bottom flask was charged with phthalimide (37.3 mg, 0.225 mmol) in a glove box. The flask was capped with a Telfon tape– twined stopper, removed from the glove box, and sealed with Parafilm wrapping around the joints. Degassed MeCN (3 mL) was then added. The flask was shaken gently until the entire white solid had dissolved. [(Phen)2Cu]BF4 solution (3.75 mM): A 50-mL round-bottom flask was charged with [(Phen)2Cu]BF4(19.2 mg, 0.0375 mmol). The flask was capped with a Telfon tape–twined stopper and further sealed with Parafilm wrapping around the joints. The flask was purged with argon three times before degassed MeCN (10 mL) was added. The flask was shaken gently until the entire dark-red solid had dissolved. Peroxide solution (0.3 M): A 50-mL round-bottom flask equipped with a magnetic stirrer bar was charged with the alkene S32 (319 mmol, 1.35 mmol) and MeOH (30 mL, 0.045 M) and then it was cooled to –78 °C in a dry-ice / acetone bath with two 250-mL waste gas trappers equipped with 20 wt% aqueous KI (200 mL). Ozone was bubbled through the solution until complete consumption of the starting material had occurred (as indicated by TLC and / or a blue color in the reaction mixture). The solution was sparged with argon for 5 min to expel excess ozone and then the mixture was warmed to room temperature and the MeOH evaporated in vacuo. The residue was dissolved in benzene (15 mL) followed by concentration in vacuo to remove adventitious water; this step wa...

Claims

Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO What is claimed is:

1. A method of making a nitrogenous compound, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine or an azide, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine or the azide through a second single bond in place of the alkene.

2. The method of claim 1, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an azide, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the azide through a second single bond in place of the alkene.

3. The method of claim 1 or 2, wherein the method is represented by Scheme Ia:Scheme Ia wherein A is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1 and R2 are each independently H, aryl (e.g., phenyl), heteroaryl, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl); or R1and A combine to form a cycloalkyl or heterocyclylalkyl;Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO XAis the oxidant; XB is the SET reagent; and XDis the azide, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1 and R2 is the alkene.

4. The method of claim 3, wherein the method is represented by Scheme I:Scheme I wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1and R2are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XA is the oxidant; XBis the SET reagent; and XD is the azide, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene.

5. The method of claim 1, comprising: contacting a starting compound comprising an sp3-hybridized carbon connected to an alkene through a first single bond with an oxidant, thereby forming an oxidized starting compound; contacting the oxidized starting compound with a single-electron-transfer (SET) reagent, in the presence of an amine, thereby forming the nitrogenous compound; and wherein the sp3-hybridized carbon atom of the nitrogenous compound is bound to the amine through a second single bond in place of the alkene.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 6. The method of claim 1 or 5, wherein the method is represented by Scheme IIa:Scheme IIa wherein A is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1 and R2 are each independently H, aryl (e.g., phenyl), heteroaryl, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl); or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XA is the oxidant; XB is the SET reagent; and XCis the amine, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1 and R2 is the alkene.

7. The method of claim 6, wherein the method is represented by Scheme II:Scheme II wherein A is alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1and R2are each independently H, alkyl (e.g., methyl), or hydroxyalkyl (e.g., hydroxymethyl) or R1 and A combine to form a cycloalkyl or heterocyclylalkyl; XA is the oxidant; XBis the SET reagent; andAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO XCis the amine, wherein A comprises the sp3-hybridized carbon, the wavy bond is the first single bond, and the ethylene unit bearing R1and R2is the alkene.

8. The method of any one of claims 1-7, wherein the first single bond and the second single bond are located in the same position of the sp3-hybridized carbon.

9. The method of any one of claims 1-8, wherein the oxidant is ozone.

10. The method of any one of claims 1-9, wherein the SET reagent comprises a first-row transition metal salt and a ligand, preferably a bidentate ligand.

11. The method of claim 10, wherein the ligand is selected from 1,10-phenanthroline, bathophenanthroline, 4,7-dimethoxy-1,10-phenanthroline, 3,5,6,8-tetrabromo-1,10- phenanthroline, 1,10-phenanthroline-5,6-dione, 4,4’-di-tert-butyl-2,2’-bipyridine, (1S,2S)- N1,N2-dimethylcyclohexane-1,2-diamine, 3,4,7,8-tetramethylphenanthroline, triphenylphosphine, 4,7-di(pyrrolidin-1-yl)-1,10-phenanthroline, 4,7-dichloro-1,10- phenanthroline, 3,8-dibromo-1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, 3,8- dimesityl-1,10-phenanthroline, 2,2'-bipyridine, 4,4'-dimethoxy-2,2'-bipyridine, (2E,3E)- N2,N3-dimesitylbutane-2,3-diimine, (2E,3E)-N2,N3-diphenylbutane-2,3-diimine, 2,6-bis((R)- 4-phenyl-4,5-dihydrooxazol-2-yl)pyridine, (4S,4'S)-2,2'-(propane-2,2-diyl)bis(4-phenyl-4,5- dihydrooxazole), (4R,4'R)-2,2'-(propane-2,2-diyl)bis(4-phenyl-4,5-dihydrooxazole), and 1,2- bis(diphenylphosphino)ethane.

12. The method of claim 11, wherein the ligand is 1,10-phenanthroline.

13. The method of any one of claims 10-12, wherein the first-row transition metal salt is selected from FeCl2, FeBr2, FeSO4, CuCl, CuBr, CuI, CuOAc, Cu(MeCN)4BF4, Cu(MeCN)4PF6, Cu₂O, CuOTf, CuCl2, CuBr2, CuSO₄, CuO, Cu(OAc)2, Cu(acac)2and Cu(OTf)2.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 14. The method of claim 13, wherein the first-row transition metal salt is selected from FeCl2, FeBr2, FeSO4, CuCl, CuBr, CuI, CuOAc, Cu(MeCN)4BF4, CuCl2, Cu(OAc)2, and Cu(OTf)2.

15. The method of claim 14, wherein the first-row transition metal salt is CuCl.

16. The method of any one of claims 1-15, wherein the SET reagent is a transition metal complex.

17. The method of any one of claims 1-16, wherein the SET reagent is a copper complex.

18. The method of any one of claims 1-17, wherein contacting the starting compound with the oxidant is performed in a primary alcohol (e.g., methanol) solvent.

19. The method of any one of claims 1-18, wherein the SET reagent is present in a substoichiometric (e.g., catalytic) quantity (e.g., about 1-50 mol% relative to the starting compound).

20. The method of claim 19, wherein the SET reagent is present at a concentration of about 1 mol%, about 2 mol%, about 5 mol%, about 10 mol%, about 15 mol%, about 20 mol%, about 25 mol%, about 30 mol%, about 35 mol%, about 40 mol%, about 45 mol%, or about 50 mol%.

21. The method of claim 20, wherein the SET reagent is present at a concentration of about 20 mol%.

22. The method of any one of claims 1-21, wherein the method is performed in an inert atmosphere (e.g., N2or Ar).

23. The method of any one of claims 1-22, wherein contacting the starting compound with the oxidant is performed at about -50 ℃, about -60 ℃, about -70 ℃, about -80 ℃, or about -90 ℃.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 24. The method of any one of claims 1-23, wherein contacting the oxidized starting compound with the SET reagent is performed at about 15 ℃, about 20 ℃, about 25 ℃, about 30 ℃, about 40 ℃, about 50 ℃, or about 60 ℃.

25. The method of any one of claims 1-24, wherein contacting the oxidized starting compound with the SET reagent is performed at ambient temperature.

26. The method of any one of claims 1-25, wherein the starting compound is represented by Formula Ia:Ia or a salt thereof, wherein RA is alkyl, heteralkyl, deuteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1is H, alkyl, deuteroalkyl (e.g., deuteromethyl), aryl, or heteroaryl; or RAand R1combine to form a cycloalkyl; and R2 is H, alkyl, or hydroxyalkyl.

27. The method of claim 26, wherein the starting compound is represented by Formula I:I or a salt thereof, wherein RAis alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), or heteralkyl(cycloalkyl); R1 is H, alkyl, or deuteroalkyl (e.g., deuteromethyl); or RA and R1 combine to form a cycloalkyl; and R2is H or hydroxyalkyl.

28. The method of claim 26 or 27, wherein R1 is deuteromethyl.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 29. The method of any one of claims 1-28, wherein the starting compound is represented by Formula Ib: Ib or a salt thereof.

30. The method of any one of claims 1-29, wherein the starting compound is represented by Formula Ic:Ic or a salt thereof, wherein RX is alkyl (e.g., methyl), hydroxyl, halo (e.g., chloro, bromo, or fluoro), cycloalkyl (e.g., cyclohexyl), aminoalkyl, or amidoalkyl; X1is NRZor C(RB)(RC); RB or RC are each independently H or alkyl; or RB and R4 combine to form a heterocyclyl (e.g., epoxyl); or Rc and R4 combine to form a heterocyclyl (e.g., epoxyl); R4is H; R3 is alkyl (e.g., methyl); RZ is H, alkyl, aryl, ester (e.g., tert-butyloxycarbonyl), or sulfonyl (e.g., tosyl); m1 is 0, 1, 2, 3 or 4; and n1 is 0, 1, 2, 3, 4, 5, 6, 7, or 8.

31. The method of claim 30, wherein RZ is tert-butyloxycarbonyl.

32. The method of claim 30, wherein RZis tosyl.

33. The method of any one of claims 30-32, wherein R3 is methyl.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 34. The method of any one of claims 30-33, wherein RBand R4combine to form a heterocyclyl (e.g., epoxyl).

35. The method of any one of claims 30-33, wherein Rcand R4combine to form a heterocyclyl (e.g., epoxyl).

36. The method of any one of claims 30-35, wherein RX is methyl.

37. The method of any one of claims 30-35, wherein RX is hydroxyl.

38. The method of any one of claims 1-37, wherein the starting compound is represented by Formula Id: Id or a salt thereof, wherein n2 is 0, 1, 2, 3, 4, 5, 6, 7, or 8.

39. The method of any one of claims 1-38, wherein the starting compound is a terpene.

40. The method of any one of claims 1-39, wherein the starting compound is (+ / - / ±)- isopulegol, (+ / - / ±)-β-pinene, (+ / - / ±)-sabinene, (+ / - / ±)-β-citronellol, (+ / - / ±)-sclareol, (+ / - / ±)- dihydromyrcenol, (+ / - / ±)-carveol, (+ / - / ±)-nootkatone, cis-(+ / - / ±)-limonene oxide, α- methylstyrene, or α-trideuteromethylstyrene.

41. The method of any one of claims 1-40, wherein the starting compound is selectedAtty Docket No. UCH-38225 [UCLA 2024-032-2] WOthereof.

42. The method of any one of claims 1 and 3-41, wherein contacting the oxidized starting compound with the SET reagent is performed in a polar aprotic first solvent.

43. The method of claim 42, wherein the polar aprotic first solvent is selected from acetone, dimethylformamide, acetonitrile, dichloromethane, benzene, methanol, dimethyl sulfoxide, and tetrahydrofuran, or a combination thereof.

44. The method of claim 43, wherein the polar aprotic first solvent is acetonitrile.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 45. The method of any one of claims 1 and 3-44, wherein the amine is a primary amine.

46. The method of any one of claims 1 and 3-44, wherein the amine is a secondary amine.

47. The method of any one of claims 1 and 3-46, wherein the amine is represented by Formula II: II or a salt thereof, wherein RBis aryl, hetaryl, heterocyclyl, heterocyclylalkyl, alkyl, heteralkyl, cycloalkyl, heterocycloalkyl, cycloalkyl(alkyl), cycloalkyl(heteralkyl), or cycloalkyl(aralkyl); and RYis H, alkyl, heteralkyl, cycloalkyl, or cycloalkyl(alkyl), ester (e.g., tert-butyloxycarbonyl), or sulfonyl (e.g., tosyl).

48. The method of claim 47, wherein RY is tert-butyloxycarbonyl.

49. The method of claim 47, wherein RY is tosyl.

50. The method of any one of claims 1 and 3-49, wherein the amine is a nucleoside.

51. The method of claim 50, wherein the amine is adenosine, guanosine, 5-methyluridine, uridine, cytidine, 2ʹ-deoxyadenosine, 2ʹ-deoxyguanosine, thymidine, 2ʹ-deoxyuridine, or 2ʹ- deoxycytidine.

52. The method of any one of claims 1 and 3-51, wherein the amine is selected from:Atty Docket No. UCH-38225 [UCLA 2024-032-2] WOAtty Docket No. UCH-38225 [UCLA 2024-032-2] WO53. The method of any one of claims 1-4 and 8-41, wherein the method further comprises contacting the oxidized starting compound with a photocatalyst.

54. The method of claim 53, wherein the method further comprises irradiating the oxidized starting compound after contacting the oxidized starting compound with the photocatalyst.

55. The method of claim 54, wherein the irradiating is performed at a wavelength from about 250 nm to about 1000 nm.

56. The method of claim 55, wherein the irradiating is performed at a wavelength from about 450 nm to 495 nm.

57. The method of claim 56, wherein the irradiating is performed with blue light.

58. The method of any one of claims 53-57, wherein the photocatalyst is a transition metal photocatalyst.

59. The method of any one of claims 53-58, wherein the photocatalyst is an organic photocatalyst.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 60. The method of claim 58 or 59, wherein the photocatalyst is selected from a ruthenium photocatalyst, an iridium photocatalyst, a titanium photocatalyst, a cobalt photocatalyst, a tungsten photocatalyst, and a copper photocatalyst.

61. The method of claim 60, wherein the photocatalyst is an iridium photocatalyst selected from (Ir[dF(CF3)ppy]2(dtbpy))PF6, [Ir(dtbbpy)(ppy)2]PF6, tris[2-phenylpyridinato- C2,N]iridium(III), [Ir(dF(Me)ppy)2(dtbbpy)]PF6, [Ir{dFCF3ppy}2(bpy)]PF6, Ir(dFppy)3, [Ir(dFCF3ppy)2-(5,5′-dCF3bpy)]PF6, Ir(p-CF3-ppy)3, [Ir(ppy)2(dtbpy)]PF6, dichlorotetrakis(2- (2-pyridinyl)phenyl)diiridium(III), [Ir(p-F(Me)ppy)2-(4,4′-dtbbpy)]PF6, [Ir(dFppy)2(dtbbpy)]PF6, Ir(p-F-ppy)3, Ir(p-tBu-ppy)3, (Ir[Me(Me)ppy]2(dtbpy))PF6, Ir[p- F(t-Bu)-ppy]3. Ir[dF(t-Bu)-ppy]3, Ir[FCF3(CF3)ppy]2(dtbbpy)PF6, and Ir[dFFppy]2-(4,4′- dCF3bpy)PF6.

62. The method of claim 61, wherein the photocatalyst is [Ir(ppy)2(dtbpy)]PF6. 63 The method of any one of claims 53-62, wherein the photocatalyst is present in a substoichiometric (e.g., catalytic) quantity (e.g., about 1-50 mol% relative to the starting compound).

64. The method of claim 63, wherein the photocatalyst is present at a concentration of about 1 mol%, about 2 mol%, about 5 mol%, about 10 mol%, about 15 mol%, about 20 mol%, about 25 mol%, about 30 mol%, about 35 mol%, about 40 mol%, about 45 mol%, or about 50 mol%.

65. The method of claim 64, wherein the photocatalyst is present at a concentration of about 1 mol%.

66. The method of any one of claims 53-65, wherein contacting the oxidized starting compound with the SET reagent is performed in a polar aprotic second solvent.

67. The method of claim 66, wherein the polar aprotic second solvent is selected from acetone, dimethylformamide, acetonitrile, dichloromethane, benzene, methanol, dimethyl sulfoxide, and tetrahydrofuran, or a combination thereof.Atty Docket No. UCH-38225 [UCLA 2024-032-2] WO 68. The method of claim 67, wherein the polar aprotic second solvent is acetone.

69. The method of claim 67, wherein the polar aprotic second solvent is acetonitrile, methanol, or a combination thereof.

70. The method of any one of claims 51-69, wherein the azide is represented by Formula IV: IV or a salt thereof, wherein RV is silyl.

71. The method of claim 70, wherein RVis selected from trimethylsilyl, tert- butyldimethylsilyl, and triisopropylsilyl.

72. The method of claim 71, wherein RV is trimethylsilyl.

73. A compound formed by the method of any one of claims 1-72.

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