Heterogeneous catalysts and methods of making and using same

Abstract

Heterogeneous catalysts and methods of making and using the same are described herein. For example, heterogeneous catalysts formed from diphosphine-linked copper (I) complexes on a metal organic framework support can be used in cycloaddition reactions and the like.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims the benefit and priority of U.S. Provisional Application No. 63 / 604,642, filed on November 30, 2023, the entire content of which is incorporated herein by reference. Field of the Invention

[0003] The disclosed invention generally relates to the field of heterogeneous catalysts that can be used, for example, in cycloaddition reactions. Background of the Invention

[0005] Aryl - substituted cyclobutane rings are prominent structural features of a large number of bioactive molecules (Goetzke, F.W., Hell, A.M.L., van Dijk, L. & Fletcher, S.P. A catalytic asymmetric cross - coupling approach to the synthesis of cyclobutanes. Nat. Chem. 13, 880 - 886 (2021); Dembitsky, V.M. Naturally occurring bioactive cyclobutane - containing (CBC) alkaloids in fungi, fungal endophytes, and plants. Phytomedicine 21, 1559 - 1581 (2014)), and their construction is crucial for natural product synthesis and drug discovery (Namyslo, J.C. & Kaufmann, D.E. The application of cyclobutane derivatives in organic synthesis. Chem. Rev. 103, 1485 - 1538 (2003); Wang, M. & Lu, P. Catalytic approaches to assemble cyclobutane motifs in natural product synthesis. Org. Chem. Front. 5, 254 - 259 (2018)).

[0006] The photochemical [2 + 2] cycloaddition reaction is arguably the most direct method for preparing such cyclobutane - containing compounds, which mainly relies on the activation of styrene via electron or energy transfer by transition metals or organic photosensitizers (Poplata, S., A., Zou, Y.-Q. & Bach, T. Recent advances in the synthesis of cyclobutanes by olefin [2+2] photocycloaddition reactions. Chem. Rev. 116, 9748-9815 (2016); Zhou, Q.-Q., Zou, Y.-Q., Lu, L.-Q. & Xiao, W.-J. Visible-light-induced organic photochemical reactions through energy-transfer pathways. Angew. Chem. Int. Ed. 58, 1586-1604 (2019); Sicignano, M., Rodríguez, R. I. & Alemán, J. Recent visible light and metal free strategies in [2+2] and [4+2] photocycloadditions. Eur. J. Org. Chem. 2021, 3303-3321 (2021); Zhu, M., Zhang, X., Zheng, C. & You, S.-L. Energy-transfer-enabled dearomative cycloaddition reactions of indoles / pyrroles via excited-state aromatics. Acc. Chem. Res. 55, 2510–2525 (2022)). The same type of oxidative intermolecular cross-[2+2] cycloaddition reactions have also been achieved using various polymer-based heterogeneous photocatalysts (Li, R. et al. Photocatalytic regioselective and stereoselective [2+2] cycloaddition of styrene derivatives using a heterogeneous organic photocatalyst. ACS Catal. 7, 3097–3101 (2017); Piane, J. J. et al. Organic photoredox-catalyzed cycloadditions under single-chain polymer confinement. ACS Catal. 10, 13251–13256 (2020)).Although the Yoon research group reported the first intramolecular cross-[2+2] cycloaddition of 1,2-disubstituted styrenes by triplet energy transfer catalysis in 2012 (Lu, Z. & Yoon, T. P. Visible light photocatalysis of [2+2] styrene cycloadditions by energy transfer. Angew. Chem. Int. Ed. 51, 10329–10332 (2012)), the intermolecular [2+2] cycloaddition reaction involving the formation of triplet styrene between different styrenes has only been achieved recently (Liu, Z. et al. Aggregation-enabled intermolecular photo [2+2] cycloaddition of aryl terminal olefins by visible-light catalysis. CCS Chem. 2, 582–588 (2020)). In terms of heterogeneous photocatalytic energy transfer, only quantum dots have been reported to promote the [2+2] cycloaddition of styrene (Jiang, Y., Wang, C., Rogers, C. R., Kodaimati, M. S. & Weiss, E. A. Regio- and diastereoselective intermolecular [2+2] cycloadditions photocatalysed by quantum dots. Nat. Chem. 11, 1034–1040 (2019)).

[0007] Despite the substantial progress made in triplet photosensitization over the past few decades, the development of visible-light photocatalysis for the intermolecular cross-[2+2] cycloaddition of simple styrenes with other olefins remains a major challenge.

[0008] Therefore, there is still a need for improved catalysts for use in cycloaddition reactions that can address the above problems.

[0009] Accordingly, an object of the present invention is to provide a heterogeneous catalyst having improved performance.

[0010] Another object of the present invention is to provide a method for manufacturing such a heterogeneous catalyst.

[0011] Another object of the present invention is to provide a method for effectively driving a cycloaddition reaction using such a heterogeneous catalyst. Summary of the Invention

[0012] This document describes heterogeneous catalysts that can be used in chemical reactions, such as [2+2] cycloaddition and the like. In one example, non-limiting examples of heterogeneous catalysts include:

[0013] Metal-organic frameworks formed from multiple inorganic nodes and multiple organic linkers, where at least one of the multiple organic linkers contains a phenanthroline moiety;

[0014] Where at least one copper(I) ion is connected to the phenanthroline moiety and to a phosphine ligand to form a catalyst complex within the metal-organic framework.

[0015] In certain examples, the catalyst complex within the metal-organic framework includes the following chemical structure:

[0016]

[0017] Here, those skilled in the art can understand that the wavy bond extending from the phenanthroline moiety is part of the organic linker within the metal-organic framework that contains this moiety.

[0018] The heterogeneous catalyst (i.e., a heteroleptic copper(I) complex with bidentate nitrogen and phosphorus donor ligands) can be used as a photoredox catalyst and a (high) triplet photosensitizer, and can be used in various light-mediated organic transformations. The heterogeneous catalyst can provide a high turnover number (TON) of about 50 to 5000 turnovers, as well as sub-ranges or individual values within the above range.

[0019] The heterogeneous catalyst generally has a relatively long photoexcited state lifetime. For example, the heterogeneous catalyst can have a room temperature excited state lifetime of at least about 3, 3.5, 4, 4.5, or 5 μs; or a room temperature excited state lifetime of about 3 to 5 μs, as well as sub-ranges or individual values within the above range.

[0020] The heterogeneous catalyst can be synthesized by various methods. In one example, non-limiting methods for synthesizing the heterogeneous catalyst include the following steps:

[0021] (i) Reacting multiple organic linkers with an inorganic salt to form a metal-organic framework containing multiple inorganic nodes, where at least one of the multiple organic linkers contains a phenanthroline moiety;

[0022] (ii) Metalizing the metal-organic framework by mixing a metal complex containing at least one copper(I) ion connected to a phosphine ligand with the metal-organic framework;

[0023] Where the metalization step includes causing at least one copper(I) ion to become connected to the phenanthroline moiety to form a catalyst complex within the metal-organic framework.

[0024] In another non-limiting example, a method for synthesizing a heterogeneous catalyst comprises the following steps:

[0025] (i’) metallizing a metal-organic framework by mixing a metal complex comprising at least one copper(I) ion linked to a phosphine ligand with the metal-organic framework;

[0026] wherein the metal-organic framework is formed from a plurality of inorganic nodes and a plurality of organic linkers, wherein at least one of the plurality of organic linkers comprises a phenanthroline moiety;

[0027] wherein the metallization step comprises causing at least one copper(I) ion to become linked to the phenanthroline moiety to form a catalyst complex within the metal-organic framework.

[0028] The heterogeneous catalysts described below can be used for large-scale synthesis and have been shown to have catalyst recyclability and facilitate the separation of the catalyst and the product. In addition, the heterogeneous catalysts can be used to achieve organic transformations that were not achievable in previously established photocatalytic systems, such as the intermolecular [2+2] cycloaddition of styrene with electron-deficient olefins. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1A Shows non-limiting examples of two homogeneous copper catalysts (left and middle) and a heterogeneous copper catalyst supported by a metal-organic framework (MOF).

[0030] Figure 1B Shows two non-limiting reactions that may be achieved using the heterogeneous catalyst and demonstrates high catalytic efficiency and broad substrate applicability.

[0031] Figure 2A Shows a non-limiting synthesis scheme for the synthesis of a UiO-69 type copper-based heterogeneous catalyst.

[0032] Figure 2B Shows a comparison of the PXRD patterns of UiO-69-phen(binap)Cu, UiO-69-phen(xantphos)Cu, UiO-69-phenCu, and UiO-69-phen with the simulation of the UiO-69 MOF.

[0033] Figure 2C Shows the Cu2p XPS spectra, indicating the +1 oxidation state of the Cu centers in UiO-69-phen(binap)Cu, UiO-69-phen(xantphos)Cu, and UiO-69-phenCu.

[0034] Figure 2DShows the EXAFS spectra at the Cu K-edge absorption of UiO-69-phen(binap)Cu and the fitting data in R space. χ is the fine structure function. R is the interatomic distance from Cu.

[0035] Figure 3 Shows the chemical structures of compounds Cu-1, Cu-2, Cu-3, and Cu-4.

[0036] Figure 4 Shows the study on the substrate scope of the cross-[2+2] cycloaddition reaction of styrene with electron-deficient alkenes. Reaction conditions: Styrene (0.2 mmol, 1.0 equiv), electron-deficient alkene (3.0 or 5.0 equiv), UiO-69-phen(binap)Cu (0.2 mol%), and DMAP (1.2 equiv) in anhydrous DCE (1 ml) under a nitrogen atmosphere at room temperature irradiated with blue LED light (440 nm) for 48 h. For each entry number (bold), the data are reported as isolated yields. The diastereomeric ratio was determined by 1 1H NMR analysis. a Use 0.75 mol% catalyst. b Use dimethyl fumarate (1.2 equiv). c Use 1.5 mol% catalyst. Experimental details are shown in Example 1. d Use 0.5 mol% catalyst. DMAP, 4-dimethylaminopyridine; DCE, 1,2-dichloroethane; tBu, tert-butyl; Bn, benzyl; Bpin, (pinacolato)boranyl.

[0037] Figure 5 Shows the study on the substrate scope of the [2+2] cycloaddition between different styrenes. Reaction conditions: Styrene (2.0 mmol, 1.0 equiv), another styrene (5.0 equiv), UiO-69-phen(binap)Cu (0.02 mol%), and DMAP (1.2 equiv) in anhydrous DCE (1 ml) under a nitrogen atmosphere at room temperature irradiated with blue LED light (440 nm) for 48 h. For each entry number (bold), the data are reported as isolated yields. The diastereomeric ratio was determined by 1 1H NMR analysis. DMAP, 4-dimethylaminopyridine; DCE, 1,2-dichloroethane; Ac, acetyl; i Pr, isopropyl.

[0038] Figure 6Disclosed is a study on the substrate scope of the cross-[2+2] cycloaddition of exocyclic aryl azetidines, thietanes, and oxetanes with electron-deficient alkenes and styrenes. Reaction conditions: exocyclic aryl azetidine, thietane, or oxetane (0.2 mmol, 1.0 equiv), electron-deficient alkene or styrene (3.0 equiv), UiO-69-phen(binap)Cu (0.2 mol%), and DMAP (1.2 equiv) in anhydrous DCE (1 mL) under nitrogen atmosphere at room temperature irradiated with blue LED light (440 nm) for 48 h. For each entry number (bold), the data are reported as isolated yields. The diastereomeric ratio was determined by 1 1H NMR analysis of the crude reaction mixture. a Containing 0.75 mol% catalyst. b Using 1 mol% catalyst. c Using 0.5 mol% catalyst. d The diastereomeric ratio was determined after purification by silica gel column chromatography. DMAP, 4-dimethylaminopyridine; DCE, 1,2-dichloroethane; Boc, tert-butoxycarbonyl; Bn, benzyl; Ac, acetyl; Bpin, (pinacolato)boron.

[0039] Figure 7A Shows the photostability test parameters and results of the binap-linked copper species in compound Cu-2.

[0040] Figure 7B Shows the photostability test parameters and results of the binap-linked copper species in UiO-69-phen(binap)Cu.

[0041] Figure 7C Shows a graph of the cross-[2+2] cycloaddition cycle experiment of 1-vinylnaphthalene with acrylonitrile, showing the yields of six catalytic runs.

[0042] Figure 7D Shows a comparison of the PXRD patterns of the pristine and recycled UiO-69-phen(binap)Cu.

[0043] Figure 8A Shows the solid-state emission spectra (excitation wavelength: 420 nm) of UiO-69-phen(binap)Cu and Cu-1 recorded in an argon environment at room temperature.

[0044] Figure 8B Shows the exclusion of the proposed electron transfer pathway.

[0045] Figure 8C Shows two triplet excited state quenching experiments.

[0046] Figure 8DShows the mechanism of the proposed heterogeneous photocatalytic [2+2] cycloaddition reaction.

[0047] Figure 9 Shows the thermogravimetric (TGA) plots of various UiO-69 type materials in N 2 atmosphere. The percentages represent the weight loss at 200 °C. Detailed implementation

[0048] This document describes heterogeneous catalysts and methods for their manufacture and use.

[0049] I. Definitions

[0050] "Aryl" or "aryl group" should be understood to refer to a group containing a structure composed of 6 to 30 carbon atoms, 6 to 18 carbon atoms, which is formed by an aromatic ring or multiple fused aromatic rings. Exemplary aryls are but not limited to phenyl, naphthyl, anthracenyl or phenanthryl. An aryl can be unsubstituted, where all substitutable carbon atoms carry hydrogen atoms. Alternatively, they can be substituted at one, more than one or at all substitutable positions therein. Suitable exemplary substituents include but are not limited to alkyl groups, such as alkyl groups having 1 to 8 carbon atoms, which can be selected from methyl, ethyl, isopropyl or tert-butyl, aryl (e.g., C 6 -aryl, which can be substituted or unsubstituted), heteroaryl (which can contain at least one nitrogen atom, such as pyridyl), alkenyl (which can contain a double bond and 1 to 8 carbon atoms), or groups with electron-donating or electron-withdrawing ability. A group with electron-donating ability is understood to refer to a group having a positive inductive (+I) and / or positive mesomeric (+M) effect, and a group with electron-withdrawing ability is understood to refer to a group having a negative inductive (-I) and / or negative mesomeric (-M) effect. Suitable groups with donor or acceptor action are halogen groups, such as F, Cl, Br, alkoxy, aryloxy, carbonyl, ester, amine, amide, CH 2 F group, CHF 2 group, CF 3 group, CN group, thio group, or SCN group.

[0051] "Heteroaryl" or "heteroaryl group" shall be understood to mean a group which differs from the above-mentioned aryl group in that at least one carbon atom in the structure constituting the aryl group is replaced by at least one heteroatom. The heteroatom may have a hydrogen substituent and / or any permissible organic compound substituent to satisfy the valence of the heteroatom. Exemplary heteroatoms include N, O and S. In most cases, one or two carbon atoms in the aryl structure are replaced by heteroatoms. Exemplary heteroaryls include, but are not limited to, pyridyl, pyrimidinyl, pyrazolyl, triazolyl and five-membered heteroaromatic compound groups such as pyrrole group, furan group, thiophene group, pyrazole group, imidazole group, triazole group, oxazole group, thiazole group, etc. The heteroaryl may be unsubstituted (unsubstituted) at the substitutable positions, or substituted at one, more than one or all substitutable positions. Suitable substituents are as defined above for aryl.

[0052] "Alkyl" or "alkyl group" shall be understood to mean a group having 1 to 20 carbon atoms, 1 to 10 carbon atoms, or 1 to 8 carbon atoms. The alkyl may be branched or unbranched, and the carbon chain may optionally be interrupted by one or more heteroatoms such as N, O or S. The heteroatom may have a hydrogen substituent and / or any permissible organic compound substituent to satisfy the valence of the heteroatom. The alkyl may optionally be substituted by one or more of the substituents mentioned above for the aryl group. The alkyl may also contain one or more aryl groups thereon, where suitable aryl groups are as described above. Exemplary alkyls include, but are not limited to, methyl, ethyl, isopropyl, n-propyl, isobutyl, n-butyl, tert-butyl, sec-butyl, isopentyl, n-pentyl, sec-pentyl, neopentyl, n-hexyl, isohexyl and sec-hexyl.

[0053] "Alkenyl" or "alkenyl group" shall be understood to mean a group having 2 to 20 carbon atoms, 2 to 10 carbon atoms, or 2 to 8 carbon atoms, which may optionally be substituted and has at least one carbon-carbon double bond.

[0054] "Alkynyl" or "alkynyl group" shall be understood to mean a group having 2 to 20 carbon atoms, 2 to 10 carbon atoms, or 2 to 8 carbon atoms, which may optionally be substituted and has at least one carbon-carbon triple bond.

[0055] "Cycloalkyl" or "cycloalkyl group" shall be understood to mean a cyclic group having 3 to 20 carbon atoms, 3 to 10 carbon atoms, or 3 to 8 carbon atoms. The carbon chain of the cycloalkyl may optionally be interrupted by one or more heteroatoms such as N, O or S to form a heterocycloalkyl. The heteroatom may have a hydrogen substituent and / or any permissible organic compound substituent to satisfy the valence of the heteroatom. The cycloalkyl may be unsubstituted or substituted, i.e., substituted by one or more of the substituents mentioned herein.

[0056] "Cycloalkenyl" or "cycloalkenyl group" shall be understood to mean a cyclic group having 4 to 20 carbon atoms, 4 to 10 carbon atoms, or 4 to 8 carbon atoms, which may be optionally substituted and has at least one carbon-carbon double bond.

[0057] "Cycloalkynyl" or "cycloalkynyl group" shall be understood to mean a cyclic group having 6 to 20 carbon atoms, 6 to 10 carbon atoms, or 6 to 8 carbon atoms, which may be optionally substituted and has at least one carbon-carbon triple bond.

[0058] As used herein, "carbonyl" shall be understood to mean a moiety represented by the following general formula:

[0059]

[0060] wherein X is a chemical bond, or X represents oxygen or sulfur, and R represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, -(CH 2 ) m -R"; wherein R' represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or -(CH 2 ) m -R"; wherein R" represents hydroxy, substituted or unsubstituted carbonyl, aryl, cycloalkyl, heterocycle or polycycle; and m is 0 or an integer from 1 to 8. In the case where X is oxygen and R is as defined above, this moiety may be referred to as "carboxyl". When X is oxygen and R is hydrogen, this formula represents "carboxylic acid group". In the case where X is oxygen and R' is hydrogen, this formula represents "formate group". In the case where X is oxygen and R or R' is not hydrogen, this formula represents "ester group". Generally, in the case where the oxygen atom in the above formula is replaced by a sulfur atom, this formula represents "thiocarbonyl group". In the case where X is sulfur and R or R' is not hydrogen, this formula represents "thioacid group". In the case where X is sulfur and R is hydrogen, this formula represents "thiocarboxylic acid group". In the case where X is sulfur and R' is hydrogen, this formula represents "thioformate group". In the case where X is a chemical bond and R is not hydrogen, the above formula represents "ketone group". In the case where X is a chemical bond and R is hydrogen, the above formula represents "aldehyde group". The term "substituted carbonyl" refers to a carbonyl as defined above, wherein one or more hydrogen atoms in R, R' or the group attached to this moiety are independently replaced by suitable substituents as defined below.

[0061] "Amide group" or "amido" shall be understood to mean a moiety represented by the following general formula:

[0062]

[0063] Wherein, E does not exist, or E is a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, wherein independently, E, R and R’ each independently represent hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted carbonyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted aryl group, or a substituted or unsubstituted heteroaryl group, -(CH 2 ) m -R”’, or R and R’ together with the N atom to which they are attached form a heterocycle having 3 to 14 atoms in the ring structure; R”’ can represent a hydroxyl group, a substituted or unsubstituted carbonyl group, an aryl group, a cycloalkyl group, a heterocycle or a polycycle; and m is an integer of 0 or 1-8. When E is oxygen, a “carbamate group” is formed. As understood by those of ordinary skill in the art, carbamic acid cannot be attached to another chemical substance to form, for example, an oxygen-oxygen bond or other unstable bonds.

[0064] As used herein, the term “substituted” refers to all permissible substituents of the above compounds or functional groups. Exemplary substituents include, but are not limited to, halogen, hydroxyl or any other organic group containing any number of carbon atoms (preferably 1-14 carbon atoms) and optionally containing one or more heteroatoms (such as oxygen, sulfur or nitrogen groups) in the form of a straight-chain, branched-chain or cyclic structure. Representative substituents may include alkyl, substituted alkyl (e.g., -CF 3 and -CD 3 ), alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, phenyl, substituted phenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, halogen, hydroxyl, alkoxy, formyl, substituted alkoxy, phenoxy, substituted phenoxy, aryloxy, substituted aryloxy, mercapto (-SH), substituted mercapto, arylthio, substituted arylthio, cyano, isocyano, substituted isocyano, carbonyl, substituted carbonyl, carboxyl, substituted carboxyl, carboxylates, amino, substituted amino, amide, substituted amide, sulfonyl, substituted sulfonyl, sulfonic acid, phosphoryl, substituted phosphoryl, phosphonyl, substituted phosphonyl, polyaryl, substituted polyaryl, cyclic groups (e.g., C 3 -C 20 cyclic groups), substituted cyclic groups (e.g., substituted C 3 -C 20cyclic group), heterocyclic group, substituted heterocyclic group, deuterium, trihaloalkyl (trifluoromethyl), unsubstituted diarylamino, substituted diarylamino, unsubstituted dialkylamino, substituted dialkylamino, azo group, carbonate group, nitro group, nitroso group, phosphino group, pyridyl group, NRR', SR, C(O)R, COOR, C(O)NR, SOR and SOR groups, wherein R and R' are independently selected from a hydrogen atom, a deuterium atom or any of the above substituents.

[0065] The numerical ranges disclosed in this application include, but are not limited to, ranges of carbon atoms, temperature ranges, concentration ranges, time ranges, and other ranges disclosed hereinafter. The disclosed ranges individually disclose such a range that can reasonably include every possible number, as well as any sub-ranges and combinations of sub-ranges contained therein. For example, in accordance with the disclosure herein, the disclosure of a range of carbon atoms is intended to individually disclose each possible value that the range may contain. For example, a carbon range of 1 to 10 carbons also separately discloses each carbon number within that range (1, 2, 3, 4, 5, 6, 7, 8, 9, 10 carbons), as well as any sub-ranges contained therein (2 to 4 carbons or 5 to 9 carbons).

[0066] As used herein, an "electron-withdrawing group" refers to a functional group or atom within a molecule that generally has a tendency to withdraw electron density from the rest of the molecule due to its electronegativity or its ability to attract electrons through resonance or inductive effects. Electron withdrawal can occur through different mechanisms, such as: (1) electronegativity; (2) resonance effect; (3) inductive effect. Non-limiting exemplary functional groups include a carbonyl group (C=O), a nitro group (-NO 2 ) and a halogen (e.g., -Cl, -Br, -I).

[0067] The use of the term "about" is intended to describe values that are above or below a specified value, and the term "about" modifies such values to a range of about + / - 10%; in other cases, these values may range above or below the specified value by a range of about + / - 5%. When the term "about" is used before a numerical range (i.e., about 1-5) or a series of numbers (i.e., about 1, 2, 3, 4, etc.), unless otherwise stated, it is intended to modify both ends of the numerical range and / or each number listed in the entire series.

[0068] II. Heterogeneous Catalysts

[0069] Heterogeneous catalysts that can be used in chemical reactions (such as [2+2] cycloaddition) are described herein. In one example, non-limiting examples of heterogeneous catalysts include:

[0070] Metal-organic frameworks formed from multiple inorganic nodes and multiple organic linkers, wherein at least one of the multiple organic linkers contains a phenanthroline moiety;

[0071] At least one copper(I) ion is connected to the phenanthroline moiety and to the phosphine ligand to form a catalyst complex within the metal-organic framework.

[0072] In some instances, the phosphine ligand can have a chemical structure according to the following generic formula:

[0073]

[0074] wherein Rq and Rq' are each independently selected from hydrogen, an alkyl group (such as n-Bu), an alkoxy group (such as methoxy), or an aryl group (such as phenyl); and

[0075] wherein each Ar is an aryl group, which can independently be selected from, for example, phenyl or an aromatic group. In certain instances, the aromatic group has the following chemical structure:

[0076]

[0077] wherein each Alk is independently an alkyl group (such as methyl or tert-butyl). The above chemical moieties (i.e., alkyl, alkoxy, aryl) can be substituted or unsubstituted. In certain instances, the phosphine ligand is 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (binap).

[0078] In some instances, the plurality of inorganic nodes of the heterogeneous catalyst comprises or is a [Zr 6 inorganic node. In some instances, the plurality of organic linkers of the heterogeneous catalyst comprises a terphenyl dicarboxylate organic linker. In certain instances, the terphenyl dicarboxylate organic linker comprises or is a tetramethyl-substituted terphenyl dicarboxylate organic linker. In certain instances, the tetramethyl-substituted terphenyl can be 2',2”,5',5”-tetramethyl-[1,1':4',1”:4”,1”'-terphenyl]-4,4”'-dicarboxylic acid.

[0079] The heterogeneous catalyst comprises at least one organic linker having a phenanthroline moiety, which can be derived from 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid. As used herein, "derived" relates to the molecule used for synthesizing the metal-organic framework (MOF) and is understood to become part of the MOF structure.

[0080] In a preferred instance, the metal-organic framework is the Universitetet Oslo-69 metal-organic framework. In a preferred instance, the metal-organic framework is microporous. In some instances, the metal-organic framework has at least about 1,000 m 2 g -1 、1,250 m 2 g -1 、1,500 m 2g -1 、 1,750 m 2 g -1 or 2,000 m 2 g -1 of Brunauer-Emmett-Teller (BET) surface area; or the metal-organic framework has a Brunauer-Emmett-Teller (BET) surface area in the range between about 1,000 and 2,000 m 2 g -1 and sub-ranges or individual values included within the above range. In some instances, the metal-organic framework has a pore width distribution centered at about 1.3, 1.4, 1.5, 1.6, or 1.7 nm; or the metal-organic framework has a pore width distribution in the range between about 1.2 and 1.8 nm, and sub-ranges or individual values included within the above range.

[0081] In certain instances, the catalyst complex within the metal-organic framework includes the following chemical structure:

[0082]

[0083] Here, those skilled in the art will understand that the wavy bond extending from the phenanthroline moiety is part of the organic linker within the metal-organic framework that contains this moiety.

[0084] Heterogeneous catalysts (i.e., heteroleptic copper(I) complexes with bidentate nitrogen and phosphorus donor ligands) can be used as photoredox catalysts and (high) triplet photosensitizers and can be applied to various light-mediated organic transformations. It is believed that anchoring the catalyst complex within the MOF framework can enhance the photostability of such copper-binap complexes. Heterogenization of unstable transition metal species onto such a suitable framework matrix can achieve catalyst site isolation (Rogge, S.M. et al. Metal–organic and covalent organic frameworks as single-site catalysts. Chem. Soc. Rev. 46, 3134–3184 (2017); Wei, Y.-S., Zhang, M., Zou, R. & Xu, Q. Metal–organic framework-based catalysts with single metal sites. Chem. Rev. 120, 12089–12174 (2020); Chen, W. et al. Site-isolated azobenzene-containing metal–organic framework for cyclopalladated catalyzed Suzuki-Miyuara coupling in flow. ACS Appl. Mater. Interfaces 13, 51849–51854 (2021)). For example, by incorporating binap-linked heteroleptic copper(I) species onto the organic linker of a structurally stable MOF support, it has been found possible to prevent the photoinduced decomposition of the copper triplet photosensitizer and extend its excited-state lifetime due to the confinement effect caused by the MOF (Liu, J. et al. MOF-enabled confinement and related effects for chemical catalyst presentation and utilization. Chem. Soc. Rev. 51, 1045–1097 (2022)) (see Fig. 1a). Such heterogeneous catalysts can be used for visible-light-driven [2+2] cycloaddition reactions by transferring energy to appropriate reactants.For example, the described heterogeneous catalyst can effectively promote iminyl radical-mediated reactions (Ma, B. et al. Metal–organic frameworksupported copper photoredox catalysts for iminyl radical-mediated reactions. Angew. Chem. Int. Ed. 62, e202300233 (2023)).

[0085] The heterogeneous catalyst can provide a high turnover number (TON) in the range of about 50 to 5000 turnovers, as well as sub-ranges or individual values included within the above range.

[0086] The heterogeneous catalyst typically has a relatively long photoexcited state lifetime. For example, the heterogeneous catalyst can have a room temperature excited state lifetime of at least about 3, 3.5, 4, 4.5, or 5 μs; or a room temperature excited state lifetime of about 3 to 5 μs, as well as sub-ranges or individual values within the above range.

[0087] III. Method for preparing a heterogeneous catalyst

[0088] The heterogeneous catalyst can be synthesized by various methods. In one example, a non-limiting method for synthesizing the heterogeneous catalyst includes the following steps:

[0089] (i) Reacting a plurality of organic linkers with an inorganic salt to form a metal-organic framework comprising a plurality of inorganic nodes, wherein at least one of the plurality of organic linkers comprises a phenanthroline moiety;

[0090] (ii) Metalizing the metal-organic framework by mixing a metal complex comprising at least one copper(I) ion linked to a phosphine ligand with the metal-organic framework;

[0091] wherein the metalization step comprises causing at least one copper(I) ion to become linked to the phenanthroline moiety to form a catalyst complex within the metal-organic framework.

[0092] In another non-limiting example, a method for synthesizing a heterogeneous catalyst includes the following steps:

[0093] (i’) Metalizing the metal-organic framework by mixing a metal complex comprising at least one copper(I) ion linked to a phosphine ligand with the metal-organic framework;

[0094] wherein the metal-organic framework is formed from a plurality of inorganic nodes and a plurality of organic linkers, wherein at least one of the plurality of organic linkers comprises a phenanthroline moiety;

[0095] The metallization step includes converting at least one copper(I) ion into a complex with a phenanthroline moiety to form a catalyst complex within the metal-organic framework.

[0096] In certain instances, the phosphine ligand may have the following chemical structure:

[0097]

[0098] wherein Rq and Rq' are each independently selected from a hydrogen, alkyl (e.g., n-Bu), alkoxy (e.g., methoxy), or aryl (e.g., phenyl) group; and

[0099] wherein each Ar is an aryl group, which may independently be selected from, for example, a phenyl or aromatic group. In certain instances, the aromatic group has the following chemical structure:

[0100]

[0101] wherein each Alk is independently an alkyl group (e.g., methyl or tert-butyl). The above chemical moieties (i.e., alkyl, alkoxy, aryl) may be substituted or unsubstituted. In certain instances, the phosphine ligand is 2,2'-bis(diphenylphosphino)-1,1'-binaphthalene (binap).

[0102] In certain instances, the inorganic salt used in step (i) of the first method is a zirconium salt, such as ZrCl 4 . Other inorganic salts are known to those of ordinary skill in the art. In certain instances, the plurality of inorganic nodes of the metal-organic framework comprise or are [Zr 6 inorganic nodes.

[0103] In some methods, the plurality of organic linkers of the heterogeneous catalyst formed include a terphenyl dicarboxylic acid organic linker. In certain instances, the terphenyl dicarboxylic acid organic linker comprises or is a tetramethyl-substituted terphenyl dicarboxylic acid organic linker. In certain instances, the tetramethyl-substituted terphenyl may be 2',2”,5',5”-tetramethyl-[1,1':4',1”:4”,1”'-terphenyl]-4,4”'-dicarboxylic acid.

[0104] The heterogeneous catalyst formed according to the above method includes at least one organic linker having a phenanthroline moiety, which may be derived from 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid. As used herein, "derived" refers to the molecule used to synthesize the metal-organic framework (MOF) and is understood to become part of the MOF structure.

[0105] In a preferred instance, the metal-organic framework is the Universitetet Oslo-69 metal-organic framework. In a preferred instance, the metal-organic framework is microporous.

[0106] In certain instances of the first method, step (i) is carried out in an organic solvent containing a Lewis acid and heated at a temperature of at least about 100 °C; wherein the organic solvent is optionally dimethylformamide and the Lewis acid is optionally trifluoroacetic acid.

[0107] Generally, the metallization step of the method is carried out in an organic solvent at room temperature under an inert atmosphere; optionally, wherein the organic solvent is dichloromethane, and optionally, wherein the inert atmosphere is a nitrogen atmosphere.

[0108] In certain instances of the method, the metal complex used in the metallization step is:

[0109]

[0110] Other metal complexes can be used to achieve the described heterogeneous catalyst.

[0111] In a preferred instance, the method produces a heterogeneous catalyst, wherein the catalyst complex attached to the metal-organic framework has the following chemical structure:

[0112]

[0113] Here, those skilled in the art can understand that the wavy bond extending from the phenanthroline moiety is part of the organic linker containing this moiety within the metal-organic framework.

[0114] Those skilled in the art understand that the heterogeneous catalysts synthesized by the above exemplary methods may have one or more chiral centers and thus exist in the form of one or more stereoisomers. Such stereoisomers can exist as a single enantiomer, a mixture of diastereomers, or a racemic mixture and are encompassed by the present disclosure. As used herein, the term "stereoisomer" refers to a compound composed of the same atoms having the same bond order but having different three-dimensional arrangements of atoms that are not interchangeable. This three-dimensional structure is called configuration. As used herein, the term "enantiomer" refers to two stereoisomers that are non-superimposable mirror images of each other. As used herein, the term "optical isomer" is equivalent to the term "enantiomer". As used herein, the term "diastereomer" refers to two stereoisomers that are neither mirror images nor superimposable. The terms "racemate", "racemic mixture", or "racemic modification" refer to a mixture of equal portions of enantiomers. The term "chiral center" refers to a carbon atom to which four different groups are attached. Selecting a suitable chiral column, eluent, and the conditions necessary to achieve the separation of enantiomer pairs using standard techniques is well known to those of ordinary skill in the art (see, for example, Jacques, J. et al., "Enantiomers, Racemates, and Resolutions", John Wiley and Sons, Inc. 1981).

[0115] For the described methods, those of ordinary skill in the field of synthetic chemistry can select or modify the synthesis conditions (such as the choice of solvent, temperature, atmosphere, post-treatment conditions, purification conditions, etc.) as needed.

[0116] The heterogeneous catalysts formed can be characterized using suitable techniques known to those skilled in the art. The heterogeneous catalysts synthesized according to the described methods can be analyzed by 1 H and 13 C NMR, ICP-AES, BET analysis, powder XRD, EDS, XPS, EXAFS, TGA, and combinations thereof, but not limited thereto.

[0117] IV. Methods Using Heterogeneous Catalysts

[0118] The heterogeneous catalysts can be used for large-scale synthesis and have been demonstrated to have catalyst recyclability and facilitate the separation of the catalyst and the product. In addition, heterogeneous catalysts can be used to achieve organic transformations that cannot be achieved in previously established photocatalytic systems, such as the intermolecular [2+2] cycloaddition of styrene and electron-deficient olefins.

[0119] Currently, the cost of producing heterogeneous copper photocatalysts is about 30 to 50 times lower than that of producing commercial noble metal photocatalysts. Generally, homogeneous noble metal photocatalysts cannot be recovered after the photocatalytic reaction, while the heterogeneous catalysts can be recovered from the reaction mixture without significant loss of reactivity. Compared with the cumbersome separation processes used to remove homogeneous photocatalysts from solutions, the separation in heterogeneous photocatalysis can be achieved by filtration methods known to those skilled in the art.

[0120] In a non-limiting example, the heterogeneous catalyst can be used for [2+2] cycloaddition in a method comprising the following steps:

[0121] (a) forming a mixture of a first compound and a second compound in an organic solvent comprising one or more of the heterogeneous catalysts described herein;

[0122] wherein the first compound and the second compound each comprise a carbon-carbon double bond capable of undergoing [2+2] cycloaddition; and

[0123] (b) exposing the mixture to visible light irradiation to photoexcite the heterogeneous catalyst, wherein energy transfer from the photoexcited heterogeneous catalyst initiates [2+2] cycloaddition between the carbon-carbon double bonds of the first compound and the second compound.

[0124] As discussed in the examples, cyclobutane is formed by [2+2] cycloaddition between the carbon-carbon double bonds of the first compound and the second compound.

[0125] In some examples of the method, at least one of the first compound and the second compound is an electron-deficient olefin or comprises an electron-deficient olefin. In other examples, at least one of the first compound and the second compound is a styrene compound or a vinylnaphthalene compound, which may be substituted. In other examples, at least one of the first compound and / or the second compound comprises an α,β-unsaturated carbonyl. In certain examples, at least one of the first compound and / or the second compound has the following chemical structure:

[0126]

[0127] wherein EWG is an electron-withdrawing group. The electron-withdrawing group can be selected from, but not limited to, -C(O)OR; -C(O)R'; -C(O)NR 1 R 2 or -CN; wherein R, R', R 1 and R 2 are each independently selected from hydrogen; halogen groups (i.e., -F, -Cl, -Br, -I); C 1 -C 5Alkyl (linear or branched), such as methyl, ethyl, propyl, butyl or pentyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxy; aryl (i.e., phenyl); heteroaryl; benzyl; acyl; ester group; carbonyl; carboxylate group; amino (primary, secondary or tertiary amino); amide group; and nitro. In other examples, at least one of the first compound and / or the second compound may have a chemical structure according to any one of formulas (I)-(IV):

[0128]

[0129] wherein A, B, C, D and E are each independently selected from hydrogen, halogen groups (i.e., -F, -Cl, -Br, -I); C 2 -C 5 Alkyl (linear or branched), such as methyl, ethyl, propyl, butyl or pentyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxy; alkoxy, such as methoxy, ethoxy, propoxy or butoxy; aryl (i.e., phenyl); heteroaryl; benzyl; acyl; ester group; carbonyl; carboxylate group; amino (primary, secondary or tertiary amino); amide group; and nitro; optionally wherein A and B; B and C; C and E; E and D may combine to form cycloalkyl, heterocycloalkyl, aryl or heteroaryl;

[0130] wherein Rx and Ry are each independently selected from hydrogen or alkyl (e.g., methyl);

[0131] wherein Ra, Ra', Ra", Rb, Rb' and Rb" are each independently selected from hydrogen, hydrogen, halogen groups (i.e., -F, -Cl, -Br, -I); C 2 -C 5 Alkyl (linear or branched), such as methyl, ethyl, propyl, butyl or pentyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxy; alkoxy, such as methoxy, ethoxy, propoxy or butoxy; aryl (i.e., phenyl); heteroaryl; benzyl; acyl; ester group; carbonyl; carboxylate group; amino (primary, secondary or tertiary amino); amide group; and nitro;

[0132] wherein Q, Q', X, X', Z and Z' are each independently selected from hydrogen and alkyl; optionally, wherein Q and Z and Q' and Z' may combine to form cycloalkyl or heterocycloalkyl;

[0133] wherein the carbon of the aromatic ring of formula (I), (III), (IV) or (V) is optionally substituted by nitrogen.

[0134] As described above, various combinations of the first compound and the second compound including carbon-carbon double bonds capable of undergoing [2+2] cycloaddition are possible.

[0135] In some instances of the method, the concentration of the heterogeneous catalyst present in the mixture is about 0.01 to 2 mol% of the total mixture. In some instances, the mixture further comprises 4-dimethylaminopyridine.

[0136] In some instances, the visible light irradiation comprises blue light, wherein the blue light can have a wavelength of 440 nm or comprise a wavelength of 440 nm.

[0137] In certain instances, the organic solvent is 1,2-dichloroethane or comprises 1,2-dichloroethane. Other suitable organic solvents can also be used.

[0138] Step (b) is typically carried out under an inert atmosphere, wherein the inert atmosphere can be a nitrogen atmosphere. Other suitable inert atmospheres (i.e., argon, etc.) can also be used.

[0139] For the method, a further step of recovering the heterogeneous catalyst from the mixture can be carried out after step (b). As described above, such recovery can be accomplished using filtration techniques known in the art. The recovered heterogeneous catalyst can be reused for at least one, two, three, four, five, six or more additional [2+2] cycloadditions without loss of reactivity or significant loss of reactivity. As used herein, "significant loss" means that the loss of reactivity does not exceed about 10%, 20%, 30%, 40% or 50% compared to the reactivity during the first use.

[0140] The heterogeneous catalyst can provide a high turnover number (TON) in catalyzing the cycloaddition product, wherein the TON can be in the range of about 50 to 5000 turnover numbers, as well as sub-ranges or individual values included within the above range.

[0141] Those skilled in the art will understand that the [2+2] cycloaddition products synthesized using the heterogeneous catalyst described above may have one or more chiral centers and thus exist in the form of one or more stereoisomers. Such stereoisomers can exist as single enantiomers, mixtures of diastereomers, or racemic mixtures, and are encompassed by the present disclosure. As used herein, the term "stereoisomer" refers to a compound composed of the same atoms having the same bond order but having different non-interchangeable three-dimensional arrangements of the atoms. This three-dimensional structure is called configuration. As used herein, the term "enantiomer" refers to two stereoisomers that are non-overlapping mirror images of each other. As used herein, the term "optical isomer" is equivalent to the term "enantiomer". As used herein, the term "diastereomer" refers to two stereoisomers that are neither mirror images nor overlapping. The terms "racemate", "racemic mixture", or "racemic variant" refer to a mixture of equal portions of enantiomers. The term "chiral center" refers to a carbon atom to which four different groups are attached. Selecting a suitable chiral column, eluent, and the conditions necessary to achieve the separation of enantiomer pairs using standard techniques is well known to those of ordinary skill in the art (see, for example, Jacques, J. et al., "Enantiomers, Racemates, and Resolutions", John Wiley and Sons, Inc. 1981).

[0142] For the above methods, those of ordinary skill in the field of synthetic chemistry can select or modify the synthesis conditions (such as the choice of solvent, temperature, atmosphere, treatment conditions, purification conditions, etc.) as needed.

[0143] In certain instances, using a heterogeneous catalyst can provide [2+2] cycloaddition products with high diastereoselectivity. In certain instances, diastereoselectivity is defined as the diastereomer ratio (d.r.), which can range from >1:1 to about 10:1 between the resulting diastereomeric products, as well as sub-ranges or individual values within the above range.

[0144] The heterogeneous catalysts and methods described herein are further illustrated in the following examples, which are for illustration only and are not intended to be limiting. It should be understood that variations in the proportions of the components shown and substitutions of elements will be apparent to those skilled in the art and are within the scope of the disclosed form. When presenting theoretical aspects, the applicant does not seek to be bound by the proposed theory.

[0145] Examples

[0146] Example 1: Heterogeneous Copper-Based Photocatalyst for [2+2] Cycloaddition

[0147] Materials and Methods:

[0148] General Considerations:

[0149] The PXRD patterns were recorded using a Rigaku Ultima IV X-ray diffractometer (CuKα, ) at 40 kV and 30 mA. The measurement parameters included a scan speed of 10° min -1 , a step size of 0.05°, and a scan range of 2θ from 5° to 40°.

[0150] Scanning electron microscopy (SEM) and energy-dispersive spectroscopy (EDS) mapping were performed on a VEGA3 TESCAN (Japan). X-ray photoelectron spectroscopy (XPS) surface studies were carried out on a Thermo ESCALAB 250Xi system, and the spectra were analyzed using Thermo Scientific Avantage Data System software. Transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) analysis were performed by FEI-Talos F200S.

[0151] Inductively coupled plasma atomic emission spectroscopy (ICP-AES) measurements were carried out on a Thermo Scientific iCAP7000 ICP-AES analyzer.

[0152] Thermogravimetric analysis (TGA) was performed using a Mettler-Toledo (TGA / DSC1) thermal analyzer (Q50 V20.6). Approximately 5 mg of the dried sample was measured from 40 to 800 °C under the conditions of an N 2 flow rate of 20 ml min -1 and a heating rate of 10 °C min -1 .

[0153] X-ray diffraction data of single crystals were collected at 173 K on an XtaLab PROMM007HF DW diffractometer system equipped with a MicroMax-007DW MicroFocus X-ray generator and a Pilatus 200K silicon double array detector (Rigaku, Japan, CuKα, ). The structure was solved by the direct method using the SHELXT program, and the anisotropic displacement parameters of all non-hydrogen atoms were refined by full-matrix least-squares on F 2 using the SHELXL program.

[0154] X-ray absorption fine structure (XAFS) measurements were carried out at beamlines 01B1 and 14B2 of SPring-8 at the Japan Synchrotron Radiation Research Institute (8 GeV, 99.5 mA). Under atmospheric conditions, Cu K-edge XAFS spectra (20 minutes for each spectrum) were recorded in fluorescence mode using an ionization chamber with Si(111), and detuning was performed to reduce the contribution of higher harmonics below the noise level. A metal foil standard was used as a reference for energy calibration and was measured simultaneously with the experimental samples. I 0 and I f The detectors used ionization chambers filled with N 2 (100%) and N 2 (70%) / Ar(30%). The XAFS results were processed according to standard procedures using the ATHENA module in the IFEFFIT software package. The k 3 -weighted EXAFS spectra were obtained by subtracting the post-edge background from the overall absorption and then normalizing according to the edge jump step. Subsequently, the k -weighted χ(k) data of the Cu K-edge were Fourier-transformed into R space to separate the EXAFS contributions from different coordination shells. To obtain the quantitative structural parameters around the central atom, least-squares curve parameter fitting was performed using the ARTEMIS module in the IFEFFIT software package. By optimizing the amplitude factor S 3 common to all paths and the energy shift ΔE 0 2 as well as the bond length (ΔR) and Debye-Waller factor (σ 0 ) parameters were refined. The fitting models for the Cu sites in UiO-69-phen(binap)Cu and UiO-69-phen(xantphos)Cu were based on the crystal structures of Cu-1 (CCDC: 2240330) and Cu-3 (CCDC: 2244329), respectively. 2 ) parameters were refined. The fitting models for the Cu sites in UiO-69-phen(binap)Cu and UiO-69-phen(xantphos)Cu were based on the crystal structures of Cu-1 (CCDC: 2240330) and Cu-3 (CCDC: 2244329), respectively.

[0155] The solid-state UV-Vis absorption spectra of the framework materials were recorded at room temperature using a UV-2550 spectrophotometer (SHIMADZU, Japan). The steady-state emission spectra were measured using a Horiba FluoroMax-3 spectrophotometer. The lifetimes were measured using a Quanta Ray GCR150-10 PULSED Nd:YAG laser system.

[0156] Brunauer-Emmett-Teller (BET) surface area analysis was carried out on a micromeritics surface area analyzer (ASAP2420) at 77 K.

[0157] Cyclic voltammetry was performed on a CHI760E electrochemical workstation. A conventional three-electrode system was used. The measurements were recorded under N 4 protection in a DMF solution of (Bu 4 N)(ClO -1 )(0.1 M) at a scan rate of 100 mV s 2 . A glassy carbon disk (d = 0.3 cm) was used as the working electrode, and a platinum plate (1 cm × 1 cm) was used as the counter electrode. An Ag / AgCl (3 M KCl) electrode was used as the reference electrode in all experiments, and its potential (-0.53 V vs. Fc+ / Fc) was calibrated with the ferrocenium / ferrocene (Fc + / Fc) redox couple.

[0158] 1 H and 13 C NMR spectra were recorded on a Bruker 500 or Bruker 400 spectrometer in CDCl 3 , DMSO-d 6 or a mixed deuterated solvent.

[0159] High-resolution electron ionization (EI) mass spectra were recorded on a Thermo Scientific DFS magnetic sector GC-HRMS system. High-resolution electrospray ionization mass spectrometry (ESI-MS) measurements were performed on a Bruker impact II high-resolution LC-QTOF mass spectrometer. The accurate masses of the molecular ion [M] + or [M+H] + were reported.

[0160] Synthesis of the catalyst support UiO-69-phen:

[0161] ZrCl 4 (179 mg, 0.77 mmol), 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid (L2) (50 mg, 0.12 mmol), 2',2”,5',5”-tetramethyl-[1,1':4',1”:4”,1”'-terphenyl]-4,4”'-dicarboxylic acid (L3) (270 mg, 0.60 mmol) and trifluoroacetic acid (0.4 ml) were ultrasonically dispersed in N,N-dimethylformamide (DMF) (34 ml). The resulting solution was heated to 100 °C in a 50 ml glass tube and maintained for 72 h. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with DMF and acetone. Then UiO-69-phen was collected by filtration and dried in air to give a white solid (389 mg, 60% yield based on the linker). The product (2 mg) was dissolved in saturated K 3 PO 4 / D 2 O solution and DMSO-d 6 (0.6 ml, 1:2 v / v) and subjected to 1 1H NMR analysis. The ratio of L2 and L3 was found to be 1:5. Based on the NMR digestion data and TGA, the chemical formula of UiO-69-phen was determined to be Zr 6 O 4 (OH) 4 (L2)(L3) 5 ·4.0 DMF.

[0162] Synthesis of catalyst UiO-69-phenCu:

[0163] UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in 2 ml of [Cu(MeCN) 4 (PF 6 )(10.4 mg, 28 μmol) in dichloromethane solution, and stirred at 60 °C for 4 hours under N 2 atmosphere. After cooling to room temperature, the supernatant was decanted, and the solid was washed five times with DMF and acetone. Then UiO-69-phenCu was collected by filtration, air-dried, and a green solid (22.7 mg, 93% yield) was obtained. ICP-AES analysis showed that the Zr / Cu ratio was 6:1. Based on ICP-AES and TGA, the chemical formula of UiO-69-phenCu was determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(CH 3 CN) 2 PF 6}·4.4 DMF.

[0164] Synthesis of catalyst UiO-69-phen(xantphos)Cu:

[0165] UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in 2-ml [Cu(xantphos)(MeCN) 2 (PF 6 )(24.3 mg, 28 μmol) in dichloromethane solution, and stirred at room temperature for 9 hours under N 2 atmosphere. After metallization after synthesis, the supernatant was decanted, and the solid was washed five times with DMF and acetone. Then UiO-69-phen(xantphos)Cu was collected by filtration and dried in air, and a yellow solid (30.9 mg, 91% yield) was obtained. ICP-AES analysis showed that the Zr / Cu ratio was 6:1. The product (2 mg) was dissolved in D3 PO 4 / D 2 O / DMSO-d 6 (1:1:5 v / v / v) solution, and perform 1 H NMR analysis. It was found that the ratio of Cu-4 to L3 was 1:5. According to the NMR digestion data and TGA, the chemical formula of UiO-69-phen(xantphos)Cu was determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(xantphos)PF 6}·4.9 DMF.

[0166] Synthesis of catalyst UiO-69-phen(binap)Cu:

[0167] UiO-69-phen (300 mg, 56 μmol based on L2) was immersed in 20-ml dichloromethane solution of [Cu(binap)(MeCN) 2 (PF 6 )(256 mg, 0.28 mmol), and stirred at room temperature for 9 hours under N 2 atmosphere. After metallization after synthesis, the supernatant was decanted, and the solid was washed five times with DMF and acetone. Then UiO-69-phen(binap)Cu was collected by filtration and dried in air to obtain a yellow solid (312 mg, 94% yield). ICP-AES analysis showed that the Zr / Cu ratio was 6:1. The product (2 mg) was dissolved in D 3 PO 4 / D 2 O / DMSO-d 6 (1:1:5 v / v / v) solution, and perform 1 H NMR analysis. It was found that the ratio of Cu-2 to L3 was 1:5. According to the NMR digestion data and TGA, the chemical formula of UiO-69-phen(binap)Cu was determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(binap)PF 6}·6.0 DMF.

[0168] General procedure for photoinduced cross-[2+2] cycloaddition of styrene with electron-deficient alkenes:

[0169] Under N 2Under an N₂ atmosphere, UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.2 mol%), 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv), 1,2-dichloroethane (1.0 ml), styrene (0.2 mmol, 1.0 equiv), and an electron-deficient alkene (0.6 or 1.0 mmol, 3.0 or 5.0 equiv) were successively added to a cooled 25-ml direct-fire dried Schlenk tube. After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (equipped with three fans) for 48 h. After irradiation, ethyl acetate (10 ml) was added to the crude mixture; the resulting solution was filtered through a silica gel pad and washed four times with ethyl acetate (4 × 10 ml). The combined filtrates were concentrated in vacuo and the diastereomeric ratio was determined by 1 ¹H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.

[0170] General procedure for the photoinduced cross-[2+2] cycloaddition between different styrenes:

[0171] Under an N 2 ₂ atmosphere, UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.02 mol%), 4-dimethylaminopyridine (293 mg, 2.4 mmol, 1.2 equiv), 1,2-dichloroethane (1.0 ml), styrene (2.0 mmol, 1.0 equiv), and another coupling styrene (10 mmol, 5.0 equiv) were successively added to a cooled 25-ml direct-fire dried Schlenk tube. After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (equipped with three fans) for 48 h. After irradiation, ethyl acetate (10 ml) was added to the crude mixture; the resulting solution was filtered through a silica gel pad and washed four times with ethyl acetate (4 × 10 ml). The combined filtrates were concentrated in vacuo and the diastereomeric ratio was determined by 1 ¹H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.

[0172] General procedure for the photoinduced cross-[2+2] cycloaddition of exo-arylidene azetidines, thietanes, and oxetanes with electron-deficient alkenes and styrenes:

[0173] Under an N 2Under an atmosphere, UiO-69-phen(binap)Cu (2.4 mg, 0.4 μmol based on Cu, 0.2 mol%) was successively added to a cooled 25 ml direct-fire dried Schlenk tube, 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv), 1,2-dichloroethane (1.0 ml), exo-arylidene azetidine, thietane or oxetane (0.2 mmol, 1.0 equiv), and electron-deficient alkene or styrene (0.6 mmol, 3.0 equiv). After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (equipped with three fans) for 48 hours. After irradiation, ethyl acetate (10 ml) was added to the crude mixture; the resulting solution was filtered through a silica gel pad and washed four times with ethyl acetate (4 × 10 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford the corresponding product.

[0174] Gram-scale reaction:

[0175] Under an N 2 atmosphere, UiO-69-phen(binap)Cu (89 mg, 15 μmol based on Cu, 0.15 mol%) was successively added to a cooled 100 ml direct-fire dried Schlenk tube, 4-dimethylaminopyridine (1.46 g, 12 mmol, 1.2 equiv), 1,2-dichloroethane (50 ml), 1-vinylnaphthalene (1.54 g, 10 mmol, 1.0 equiv), methyl acrylate (4.5 ml, 50 mmol, 5.0 equiv). After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (equipped with three fans) for 48 hours. After irradiation, ethyl acetate (100 ml) was added to the crude mixture; the resulting solution was filtered through a silica gel pad and washed four times with ethyl acetate (4 × 50 ml). The combined filtrates were concentrated under vacuum and the diastereomeric ratio was determined by 1 1H NMR analysis. The residue was purified by flash column chromatography on silica gel to afford 1 (1.68 g, 70% yield) as a colorless oil.

[0176] Results:

[0177] Synthesis and characterization of MOF-supported copper photocatalysts:

[0178] To accommodate the sterically hindered heteroleptic copper-binap complex in a crystalline porous framework (Zhou, H.-C., Long, J. R. & Yaghi, O. M. Introduction to metal-organic frameworks. Chem. Rev. 112, 673 - 674 (2012); Furukawa, H., Cordova, K. E., O’Keeffe, M. & Yaghi, O. M. The chemistry and applications of metal-organic frameworks. Science 341, 1230444 (2013)), the highly stable Universitetet i Oslo-69 (UiO-69) MOF (Cavka, J. H. et al. A new zirconium inorganic building brick forming metal organic frameworks with exceptional stability. J. Am. Chem. Soc. 130, 13850 - 13851 (2008); Newsome, W. J. et al. Solid state multicolor emission in substitutional solid solutions of metal-organic frameworks. J. Am. Chem. Soc. 141, 11298 - 11303 (2019)) was selected as the catalyst support, and this MOF consists of [Zr 6 inorganic nodes and a terphenyl dicarboxylic acid organic linker. Considering that the binap-linked copper(I) complex is intolerant to the solvothermal conditions of MOF synthesis, a postsynthetic metallization method was adopted (Kalaj, M. & Cohen, S. M. Postsynthetic modification: an enabling technology for the advancement of metal-organic frameworks. ACS Cent. Sci. 6, 1046 - 1057 (2020); Li, J. et al. Self-adaptive dual-metal-site pairs in metal-organic frameworks for selective CO 2 photoreduction to CH 4.Nat. Catal. 4, 719 - 729 (2021); Ma, X. et al. Modulating coordination environment of single-atom catalysts and their proximity to photosensitive units for boosting MOF photocatalysis. J. Am. Chem. Soc. 143, 12220 - 12229 (2021)), rather than modifying the MOF linker before synthesis (Wang, C., Xie, Z., de Krafft, K. E. & Lin, W. Doping metal-organic frameworks for water oxidation, carbon dioxide reduction, and organic photocatalysis. J. Am. Chem. Soc. 133, 13445 - 13454 (2011); Wang, C., de Krafft, K. E. & Lin, W. Pt nanoparticles@photoactive metal-organic frameworks: efficient hydrogen evolution via synergistic photoexcitation and electron injection. J. Am. Chem. Soc. 134, 7211 - 7214 (2012)). The target copper species were introduced onto the UiO-69 MOF (Figure 2a). To prevent possible pore blockage during the metallization step, a small portion of a functionalized organic linker with a 1,10-phenanthroline (phen) moiety (i.e., 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid) was mixed with the highly soluble tetramethyl-substituted terphenyl dicarboxylic acid to synthesize the phen-functionalized UiO-69 MOF (UiO-69-phen). The crystallinity and stability of UiO-69-phen were significantly better than those synthesized using only the phen-containing linker. It had a large Brunauer-Emmett-Teller (BET) surface area of 1,990 m 2 g –1 , comparable to that of the non-functionalized UiO-69 MOF 32 , and its pore width distribution centered at 1.6 nm, laying the foundation for subsequent metallization with a cationic bisphosphine chelated copper(I) complex.

[0179] At room temperature, UiO-69-phen was immersed in dichloromethane solutions of [Cu(xantphos)(MeCN) 2 (PF 6 ) or [Cu(binap)(MeCN) 2 (PF 6 ) to generate the MOF-supported heteroleptic copper photocatalysts UiO-69-phen(xantphos)Cu or UiO-69-phen(binap)Cu. When the same metallization conditions were applied to the non-functionalized UiO-69 MOF without the phen linker, no heterogeneous copper catalyst was formed. Notably, the phen-functionalized UiO-67 MOF with a much smaller pore width distribution (Zhang, X. et al. Catalytic chemoselective functionalization of methane in a metal-organic framework. Nat. Catal. 1, 356 - 362 (2018)) could not accommodate the bulky cationic binap-linked copper(I) complex even at high temperatures. Additionally, attempts to directly encapsulate the desired copper(I) species in conventional porous hosts such as UiO-67 and UiO-68 MOFs did not yield the corresponding heterogeneous binap-containing copper photosensitizers, probably because the binap-linked copper(I) complex has low thermal stability upon heating and poor compatibility with strong Lewis acids. Treatment of UiO-69-phen with [Cu(MeCN) 4 (PF 6 ) at 60 °C produced a heterogeneous copper(I) species (UiO-69-phenCu) that was not chelated with the diphosphine ligand. According to inductively coupled plasma atomic emission spectroscopy (ICP-AES) and nuclear magnetic resonance (NMR) analyses, in each of these three cases, approximately one copper atom per [Zr 6 node was successfully loaded onto the MOF support. The copper contents determined by ICP-AES and NMR analyses were consistent, and no other phosphine-containing species were present in the NMR-digested samples, ruling out the possibility of pore blockage in the MOF by diphosphine-chelated copper(I) complexes during the post-synthetic metallization process. The N 2The adsorption isotherm indicates that the microporosity is retained despite the decrease in BET surface area. After metallization following synthesis, UiO-69 MOF maintains its typical octahedral morphology (SEM images not shown). The powder X-ray diffraction (PXRD) pattern indicates that the MOF crystallinity remains unchanged after the metallization process (Figure 2b). Energy-dispersive X-ray spectroscopy (EDS) mapping shows that copper cations are uniformly incorporated throughout the MOF crystal. The Cu2p 1 / 2 and Cu2p 3 / 2 peaks in the X-ray photoelectron spectroscopy (XPS) spectrum of the MOF-supported photocatalyst can be attributed to copper(I) species (Figure 2c). The slight shift towards the lower binding energy region is due to the coordination of the phenanthroline and diphosphine ligands to the copper center.

[0180] X-ray absorption spectroscopy at the Cu K-edge further investigated the copper coordination environment in the pores of UiO-69-phen(binap)Cu and UiO-69-phen(xantphos)Cu (Figure 2d). To better understand the binding mode of the copper(I) species in UiO-69 MOF, the extended X-ray absorption fine structure (EXAFS) data of UiO-69-phen(binap)Cu was fitted to the crystal structure of Cu-1. The best fit in the EXAFS region indicates two Cu–N bonds at and two Cu–P bonds at (Table 2 below). Each copper(I) center in UiO-69-phen(binap)Cu adopts a distorted tetrahedral geometry. Thermogravimetric analysis (TGA) (see Figure 9 ) and ICP-AES results were used to determine the copper loading in each heterogeneous photosensitizer to explore visible-light-mediated intermolecular cross-[2+2] cycloaddition.

[0181] Table 2. Summary of X-ray absorption fine structure fitting results for UiO-69-phen(binap)Cu at the Cu K-edge

[0182]

[0183] CN: Coordination number; R: Bond distance; σ 2 : Debye–Waller factor; ΔE 0 : Inner potential correction; R factor: Goodness of fit; For Cu data, S 0 2 is set to 1, which is obtained by fixing CN to the known crystallographic value and performing an experimental EXAFS fit from a Cu foil reference and is applicable to all samples.

[0184] Photocatalytic performance characterization:

[0185] It is speculated that 1-vinylnaphthalene with relatively low triplet energy undergoes energy transfer under photoexcitation of a copper catalyst and then undergoes an unprecedented [2+2] cycloaddition with methyl acrylate (Murray, P.R.D. et al. Intermolecular crossed [2+2] cycloaddition promoted by visible-light triplet photosensitization: expedient access to polysubstituted 2-oxaspiro[3.3]heptanes. J. Am. Chem. Soc. 143, 4055-4063 (2021); Coote, S.C. & Bach, T. Enantioselective intermolecular [2+2] photocycloadditions of isoquinolone mediated by a chiral hydrogen-bonding template. J. Am. Chem. Soc. 135, 14948-14951 (2013)), giving methyl trans-2-(naphthalen-1-yl)cyclobutane-1-carboxylate (1), as shown in Scheme 1 below.

[0186]

[0187] Scheme 1.

[0188] After systematically studying various reaction parameters, a procedure for obtaining the cycloaddition product using 0.2 mol% UiO-69-phen(binap)Cu was established, with a turnover number (TON) of 365 and a diastereoselectivity >10:1 (see Table 1, entry 1). Control experiments showed that the reaction did not occur in the absence of light or photocatalyst. Other MOF-supported copper(I) complexes lacking binap coordination failed to provide any cycloaddition product (Table 1, entries 2 and 3), indicating that the formation of binap-based copper(I) photosensitizers is crucial for promoting the cross-[2+2] cycloaddition. The low reactivity of the homogeneous counterparts (Cu-1 and Cu-2) highlights the importance of immobilizing heteroleptic copper(I) complexes on MOF supports to generate efficient copper photocatalysts (Table 1, entries 4-7). Although a 10-fold increase in the loading of Cu-1 or Cu-2 gave a 7% yield of 1, the corresponding homogeneous xantphos-based copper(I) photosensitizers were ineffective (Table 1, entries 8 and 9). Changing the 1,10-phenanthroline substituent in the xantphos-linked heteroleptic copper(I) complexes (Mejía, E. et al. A noble-metal-free system for photocatalytic hydrogen production from water. Chem. Eur. J. 19, 15972-15978 (2013)) did not improve their photocatalytic activity in the [2+2] cycloaddition reaction with methyl acrylate (Table 1, entries 10 and 11). The well-established [Ru(bpy) 3 (PF 6 ) 2The photocatalyst (Ischay, M. A., Lu, Z. & Yoon, T. P. [2+2] cycloadditions by oxidative visible light photocatalysis. J. Am. Chem. Soc. 132, 8572-8574 (2010)) failed to produce the desired product (Table 1, entry 12). Homogeneous iridium triplet photosensitizers with higher transition energies (Table 1, entries 13 and 14) (Lei, T. et al. General and efficient intermolecular [2+2] photodimerization of chalcones and cinnamic acid derivatives in solution through visible-light catalysis. Angew. Chem. Int. Ed. 56, 15407-15410 (2017); Zhu, M., Zheng, C., Zhang, X. & You, S.-L. Synthesis of cyclobutane-fused angular tetracyclic spiroindolines via visible-light-promoted intramolecular dearomatization of indole derivatives. J. Am. Chem. Soc. 141, 2636-2644 (2019); Girvin, Z. C. et al. Asymmetric photochemical [2+2]-cycloaddition of acyclic vinylpyridines through ternary complex formation and an uncontrolled sensitization mechanism. J. Am. Chem. Soc. 144, 20109-20117 (2022), as well as their heterogeneous equivalents (Table 1, entries 15-18) (Wang, C., Xie, Z., de Krafft, K. E. & Lin, W. Doping metal-organic frameworks for water oxidation, carbon dioxide reduction, and organic photocatalysis. J. Am. Chem. Soc.133,13445 - 13454(2011); Wang, C., de Krafft, K. E. & Lin, W. Pt nanoparticles@photoactive metal - organic frameworks: efficient hydrogen evolution via synergistic photoexcitation and electron injection. J. Am. Chem. Soc. 134, 7211 - 7214(2012); Yu, X. & Cohen, S. M. Photocatalytic metal - organic frameworks for selective 2,2,2 - trifluoroethylation of styrenes. J. Am. Chem. Soc. 138, 12320 - 12323(2016); Fan, Y., Zheng, H., Labalme, S. & Lin, W. Molecular engineering of metal - organic layers for sustainable tandem and synergistic photocatalysis. J. Am. Chem. Soc. 145, 4158 - 4165(2023)) are also incompatible with this reaction system, leading to the decomposition of a large amount of substrate. Due to the lack of carboxylic acid substituents in the styrene substrate, it is not surprising that CdSe quantum dots have been proven ineffective in the cross - [2 + 2] cycloaddition (Table 1, entry 19) (Jiang, Y., Wang, C., Rogers, C. R., Kodaimati, M. S. & Weiss, E. A. Regio - and diastereoselective intermolecular [2 + 2] cycloadditions photocatalysed by quantum dots. Nat. Chem. 11, 1034 - 1040(2019)). In addition, many heterogeneous framework - based photocatalysts and homogeneous organic photocatalysts have been investigated, which can promote the [2 + 2] dimerization of styrene mediated by electron transfer; but none of them produced any of the desired products. The catalytic results show that the binap - based copper triplet photosensitizer catalyst can promote the intermolecular cross - [2 + 2] cycloaddition of styrene and methyl acrylate, and the successful integration of these photosensitizers onto a suitable MOF support can significantly improve their photocatalytic activity.

[0189] Table 1. Effects of different catalytic systems on the cross - [2 + 2] cycloaddition

[0190]

[0191]

[0192] Conditions: 1-vinylnaphthalene (0.2 mmol, 1.0 equiv), methyl acrylate (5.0 equiv), photocatalyst (0.2 or 2 mol %), and DMAP (1.2 equiv) in anhydrous DCE (1 mL) were irradiated with a blue LED lamp (440 nm) at room temperature under a nitrogen atmosphere for 48 h. DMAP, 4-dimethylaminopyridine; DCE, 1,2-dichloroethane; dmp, 2,9-dimethyl-1,10-phenanthroline; bcp, bathocuproine; bpy, 2,2'-bipyridine; ppy, 2-(2-pyridyl)phenyl; dtbbpy, 4,4'-di-tert-butyl-2,2'-bipyridine; ppy F , 3,5-difluoro-2-(5-trifluoromethyl-2-pyridyl)phenyl; MOL-Hf-Ir(ppy F ) 2 , containing a metal-organic layer with an [Hf 12 inorganic node and an iridium-functionalized dicarboxylic acid organic linker 48 . a The yield was determined by 1 1H NMR of the crude product, using phenyltrimethylsilane as an internal standard. b The TON shown in Table 1 was calculated based on the crude NMR yield of 1. For other products, the TON was calculated based on the isolated yield. c The diastereomeric ratio (d.r.) was determined by 1 1H NMR analysis of the crude reaction mixture. d 1-Vinylnaphthalene was completely decomposed. The chemical structures of Cu-1, Cu-2, Cu-3, and Cu-4 are as Figure 3 shown.

[0193] The copper photocatalyst UiO-69-phen(binap)Cu was tested on various electron-deficient alkenes to evaluate the scope of the heterogeneous photocatalytic [2+2] cycloaddition reaction ( Figure 4 ). Many α,β-unsaturated carbonyl compounds (such as acrylates, acrylamides, vinyl alkyl ketones, and fumarates) were highly reactive and gave cross-cycloaddition products with yields up to 87% ( Figure 4 , products 1-15). In the cross-cycloaddition of various styrenes, the amount of dimethyl fumarate required could be reduced to 1.2 equiv ( Figure 4, products 8 - 15), which may be due to the more obvious electron - deficient nature of its double bond. To further investigate the scope of styrene, acrylonitrile was chosen as the reaction partner. Notably, although 1.5 mol% of UiO - 69 - phen(binap)Cu was used as the substrate with a relatively high triplet energy (Ni, T., Caldwell, R. A. & Melton, L. A. The relaxed and spectroscopic energies of olefin triplets. J. Am. Chem. Soc. 111, 457 - 464 (1989)), simple styrenes with different para - substituents still gave the cyclobutane products in high yields ( Figure 4 , products 16 - 22). Other olefins with fused aromatic rings, including quinoline and isoquinoline, participated in the highly reactive cross - [2 + 2] cycloaddition ( Figure 4 , products 23 - 28). Notably, in addition to terminal styrene, α - and β - methyl - substituted 2 - vinylnaphthalenes ( Figure 4 , products 29 and 30) and β,β - disubstituted 1 - vinylnaphthalenes ( Figure 4 , products 31 - 34) were all suitable substrates for heterogeneous copper photocatalysis. In the synthesis of spirocyclic adducts, the substrates were not limited to arylmethylene 4 - membered rings: 5 - and 6 - membered ring analogues also successfully gave the desired products with 0.75 mol% of UiO - 69 - phen(binap)Cu. Moreover, isopropenylboronic acid pinacol ester (a 1,1 - disubstituted electron - deficient olefin) gave a trisubstituted cyclobutane bearing a boron group, which could be readily transformed into other useful functional groups (He, J., Shao, Q., Wu, Q. & Yu, J. - Q. Pd(II) - catalyzed enantioselective C(sp 3 )–Hborylation. J. Am. Chem. Soc. 139, 3344–3347 (2017)) ( Figure 4 , product 35). To demonstrate the practicality of this method, the cycloaddition adduct 1 in Figure 4 was synthesized on a gram - scale using 0.15 mol% of the heterogeneous copper photocatalyst (70% yield).

[0194] For the [2 + 2] cycloaddition between different styrenes, heterogeneous copper photocatalysis was proven to be more effective ( Figure 5)。Only 0.02 mol% of UiO-69-phen(binap)Cu is required to obtain a synthetically useful yield, with a TON as high as 4750. To fully utilize the scope of styrene coupling partners and establish a library of quinoline derivatives with potential biological activity, 6-vinylquinoline was chosen as the limiting reagent in the copper-catalyzed photocycloaddition. Functional groups with different electronic properties are well tolerated at the ortho, meta, or para positions of styrene ( Figure 5 , products 36–46). A variety of heterocycles (e.g., pyridine, indole, benzofuran, and benzothiophene) can be conveniently incorporated into the final cycloaddition products ( Figure 5 , products 47–50). The cross-cycloaddition with methyl cinnamate and benzylideneacetone gives the corresponding trisubstituted cyclobutanes with high regioselectivity ( Figure 5 , products 51 and 52).

[0195] During the photosensitization of other styrenes, unsubstituted simple styrene was chosen as the coupling partner to determine the reaction scope. It was found that various substituted aryl and heterocyclic moieties are compatible with this visible-light photocatalysis ( Figure 5 , products 53–65). Notably, when bulky 1-naphthyl, 9-phenanthryl, or 4-isoquinolyl groups are introduced into the substrate, the diastereoselectivity is significantly improved (>10:1 d.r.) ( Figure 5 , products 58, 59, 61, and 63). To further demonstrate the utility of this method, substrates from bioactive molecules (i.e., (+)-menthol and formononetin) were used in the cross-[2+2] cycloaddition, giving the desired products in 64% and 85% yields, respectively ( Figure 5 , products 66 and 67).

[0196] The excellent photocatalytic activity of UiO-69-phen(binap)Cu prompted us to reinvestigate the intermolecular crossed [2+2] cycloaddition of exocyclic arylidene four-membered rings (except cyclobutane) with electron-deficient alkenes ( Figure 6 ), which was previously explored by Knowles et al. using a potent iridium(III) photosensitizer (Murray, P.R.D. et al. Intermolecular crossed [2+2] cycloaddition promoted by visible-light triplet photosensitization: expedient access to polysubstituted 2-oxaspiro[3.3]heptanes. J. Am. Chem. Soc. 143, 4055–4063 (2021)). Under the same conditions with low catalyst loading for simple styrene ( Figure 4) Various azetidine, thiethane, and oxetane substrates can react smoothly with acrylonitrile to afford the corresponding 2-azaspiro[3.3]heptane, 2-thiaspiro[3.3]heptane, and 2-oxaspiro[3.3]heptane products in good to excellent yields ( Figure 6 , products 68–76), including several challenging substrates that react in homogeneous iridium photocatalysis ( Figure 6 , products 69 and 71). Similar to the synthesis of 58, the reaction of 3-(1-naphthylmethylene)oxetane is highly diastereoselective. The reaction scope for electron-deficient alkenes is also quite broad ( Figure 6 , products 77–85). In addition to the above examples, α-acetamidoacrylate and α-fluoroacrylate can serve as effective coupling agents in the cross-ring cycloaddition, providing a straightforward method for the preparation of 2-oxaspiro[3.3]heptanes containing α-amino acid moieties and fluorine atoms ( Figure 6 , products 81 and 82).

[0197] The scope of coupling partners in the heterogeneous copper photocatalytic system can be further extended to a variety of unstudied styrenes ( Figure 6 ). Electron-donating or electron-withdrawing groups at different positions on the aromatic ring have no significant effect on the reaction yield ( Figure 6 , products 86–92). All 2-oxaspiro[3.3]heptane products bearing heteroaryl groups, such as pyridyl (93), indolyl (94), benzofuranyl (95), and benzothiophenyl (96), can be efficiently synthesized, as shown in Figure 6 . The cis isomer of 93 is completely converted to the trans isomer after purification by silica gel column chromatography, which may be due to ring-opening isomerization triggered by protonation of the pyridine moiety. This reaction protocol is also applicable to 1,1-distyrene, giving the triaryl-substituted 2-oxaspiro[3.3]heptane (97) in 83% yield, as shown in Figure 6 .

[0198] Stability and recyclability tests:

[0199] The importance of the heterogenization strategy in the design of binap-based copper photosensitizer catalysts was elucidated by a control experiment comparing the photostabilities of Cu-2 and UiO-69-phen(binap)Cu under standard reaction conditions without substrate (Figures 7a and 7b). After 24 h of blue LED light irradiation, the heteroleptic copper(I) complex (Cu-2), as the copper-functionalized linker of UiO-69 MOF, completely degraded into insoluble aggregates together with binap dioxide. In contrast, UiO-69-phen(binap)Cu showed very high stability when exposed to this light: Cu-2 was detected by NMR after digesting the MOF with deuterated phosphoric acid in a solvent mixture of deuterated water and dimethyl sulfoxide; the ratio between Cu-2 and the normal linker remained unchanged before and after light irradiation. Due to the heterogeneous nature and high photostability of UiO-69-phen(binap)Cu, it could be easily recovered by filtration and reused at least six times without loss of its photocatalytic activity (Figure 7c). The PXRD pattern (Figure 7d), microscopic image, and N 2 adsorption isotherm of the recovered copper photocatalyst indicated that UiO-69-phen(binap)Cu retained its crystal structure after photocatalysis.

[0200] Mechanistic studies:

[0201] After postsynthetic metallation with cationic binap-linked copper(I), a maximum absorption peak was observed at 449 nm in the solid-state absorption spectrum of UiO-69-phen(binap)Cu, which was the result of metal-to-ligand charge transfer transitions and appeared together with the original peak at 351 nm from the MOF support (UiO-69-phen). Compared with other heterogeneous copper photocatalysts, the absorption curve of UiO-69-phen(binap)Cu showed the highest intensity in the blue LED excitation region. Notably, the phosphorescence peak of the heterogeneous copper(I) species was blue-shifted by 33 nm compared to that of its homogeneous counterpart, and the excited-state lifetime at room temperature increased from 1.52 μs to 4.31 μs (Figure 8a). In the first triplet excited state (T 1 ) of the heteroleptic copper complex, the copper center tended to adopt a square-planar coordination rather than the tetrahedral coordination observed in the ground state (S 0 ). The geometric constraint imposed by the octahedral UiO-69 MOF increased the energy of the T 1 state and hindered the T 1 →S 0 transition. The transition energy (from 45.7 to 48.3 kcal mol -1) and the increase in excited-state lifetime (almost tripled) can greatly facilitate the energy transfer process in the intermolecular cross-[2+2] cycloaddition of styrene. On the other hand, based on the estimated excited-state redox potential of UiO-69-phen(binap)Cu, single-electron transfer between the copper active site and the styrene substrate is significantly unfavorable (Roth, H.G., Romero, N.A. & Nicewicz, D.A. Experimental and calculated electrochemical potentials of common organic molecules for applications to single-electron redox chemistry. Synlett 27, 714–723 (2016)) (Figure 8b). In addition, using trans-stilbene as a triplet energy transfer inhibitor (Cheng, X., Li, T., Liu, Y. & Lu, Z. Stereo- and enantioselective benzylic C–H alkenylation via photoredox / nickel dual catalysis. ACS Catal. 11, 11059–11065 (2021)), it was found that the cross-cycloaddition with acrylonitrile was completely inhibited; no cycloaddition product was detected (Figure 8c).

[0202] The results showed that 1-vinylnaphthalene quenched the luminescence of UiO-69-phen(binap)Cu, but not that of UiO-69-phen(xantphos)Cu, indicating that UiO-69-phen(binap)Cu had excellent activity in promoting triplet energy transfer from photoexcited copper(I) to styrene. In addition, the rate order of simple styrene was determined to be 4.28 ± 0.40, indicating that substrate aggregation occurred before photoexcitation. Collectively, the following catalytic cycle may be operative (Figure 8d). The styrene substrate aggregated in the MOF pores to form an exciplex with much lower transition energy (Liu, Z. et al. Aggregation-enabled intermolecular photo[2+2]cycloaddition of aryl terminal olefins by visible-light catalysis. CCS Chem. 2, 582–588 (2020)), which was then sensitized by the excited-state copper(I) photocatalyst through energy transfer. The resulting 1,2-triplet styrene underwent an intermolecular radical addition with an electron-deficient olefin or simple styrene to generate a 1,4-triplet biradical. After intersystem crossing (ISC), intramolecular radical recombination occurred to form the [2+2] cycloaddition product.

[0203] Conclusion:

[0204] This example details the synthesis and use of a well-defined crystalline MOF to support a heteroleptic copper(I) complex for promoting a series of intermolecular cross-[2+2] cycloadditions by energy transfer under visible-light irradiation. Incorporating a binap-containing copper triplet photosensitizer onto the MOF organic linker greatly enhanced the photostability and increased the excited-state lifetime, enabling the cycloaddition of various styrenes with electron-deficient olefins. This heterogeneous copper photocatalysis exhibited a broad substrate scope, excellent catalytic efficiency, and outstanding catalyst recyclability, as well as a general method for designing highly active copper photocatalysts for various energy-transfer-mediated organic transformations.

[0205] Specifically, the results showed that combining a binap-linked heteroleptic copper(I) complex with a microporous zirconium-based metal-organic framework (MOF) linker produced a highly stable and reusable heterogeneous photocatalyst with a longer excited-state lifetime. Under visible-light irradiation, this copper triplet photosensitizer effectively promoted multiple intermolecular cross-[2+2] cycloadditions, including the cycloaddition reaction of simple styrene with electron-deficient olefins.

[0206] Additional details of Example 1:

[0207] Synthesis of the organic linker:

[0208]

[0209] Dimethyl 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoate (L1). To a solution of 3,8-dibromo-1,10-phenanthroline (3.4 g, 10 mmol, 1.0 equiv) in 1,2-dimethoxyethane (150 mL) was added 4-(methoxycarbonyl)phenylboronic acid (5.4 g, 30 mmol, 3.0 equiv), Pd(dppf)Cl 2 (0.732 g, 1.0 mmol, 10 mol%) and CsF (6.1 g, 40 mmol, 4.0 equiv). Under N 2 atmosphere, after stirring at 110 °C for 72 h, the solid was collected by centrifugation and washed with water, chloroform, and cold acetone, respectively. The obtained crude solid was further purified by Soxhlet extraction with chloroform for 48 h, and the extract was concentrated in vacuo to give 3.1 g (7.0 mmol, 70% yield) of the white solid title compound.

[0210] 1 1H NMR (CDCl 3 , 400 MHz): δ 9.48 (s, 2H), 8.48 (s, 2H), 8.24 (d, J = 8.0 Hz, 4H), 7.94 (s, 2H), 7.88 (d, J = 8.0 Hz, 4H), 3.99 (s, 6H).

[0211] 13 13C NMR (CDCl 3 , 100 MHz): δ 166.7, 151.5, 149.3, 141.8, 134.9, 134.0, 130.5, 130.1, 128.6, 127.5, 127.4, 52.3.

[0212] HRMS (ESI) calcd for C 28 H 20 N 2 O 4 [M+H] + requires m / z 449.1496, found m / z 449.1421.

[0213] 4,4'-(1,10-Phenanthroline-3,8-diyl)dibenzoic acid (L2). To a suspension of L1 (224 mg, 0.5 mmol, 1.0 equiv) in ethanol (5.0 mL) was added dropwise NaOH (200 mg, 5 mmol, 10 equiv) dissolved in water (5.0 mL). Under N 2Under an atmosphere, the mixture was refluxed at 85 °C for 18 h. After cooling to room temperature, the solution was acidified to pH ~5 with 1 M HCl. The solid was collected by filtration, washed with water and ethanol, and dried in vacuo to give 200 mg (0.475 mmol, 95% yield) of the title compound as a pale yellow solid.

[0214] 1 H NMR(CDCl 3 , 400 MHz): δ 13.12 (brs, 2H), 9.51 (d, J = 2.0 Hz, 2H), 8.94 (d, J = 2.0 Hz, 2H), 8.19 - 8.08 (m, 10H).

[0215] 13 C NMR(CDCl 3 , 100 MHz): δ 167.0, 134.2, 130.6, 130.2, 127.6, 127.5.

[0216] HRMS(ESI) calculated for C 26 H 16 N 2 O 4 [M + H] + requires m / z 421.1183, found m / z 421.1127.

[0217]

[0218] 4'-Bromo-2',5'-dimethyl-[1,1'-biphenyl]-4-carboxylate (S1). To a suspension of 4-(methoxycarbonyl)phenylboronic acid (1.8 g, 10 mmol, 1.0 equiv), 1,4-dioxane (48 mL) and water (12 mL) was added 1,4-dibromo-2,5-dimethyl-benzene (7.9 g, 30 mmol, 3.0 equiv), Pd(dppf)Cl 2 (0.37 g, 0.5 mmol, 5.0 mol%), and K 2 CO 3 (4.1 g, 30 mmol, 3.0 equiv). After stirring at 80 °C for 8 h under a N 2 atmosphere, the reaction mixture was diluted with water and the aqueous layer was extracted with ethyl acetate (3 × 50 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate = 10:1 as the eluent to give 2.7 g (8.6 mmol, 86% yield) of the title compound as a white solid.

[0219] 1 H NMR(CDCl 3, 400 MHz): δ 8.08 (d, J = 8.4 Hz, 2H), 7.46 (s, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 3.94 (s, 3H), 2.39 (s, 3H), 2.19 (s, 3H).

[0220] 13 C NMR(CDCl 3 , 100 MHz): δ 166.9, 145.6, 140.0, 135.2, 134.4, 133.9, 131.7, 129.5, 129.1, 128.8, 124.1, 52.2, 22.3, 19.6.

[0221] HRMS(ESI) calculated for C 16 H 15 BrO 2 [M + H] + requires m / z 319.0328, found m / z 319.0306.

[0222]

[0223] Dimethyl 2',2”,5',5”-tetramethyl-[1,1':4',1”:4”,1”'-terphenyl]-4,4”'-dicarboxylate (S2). To a solution of S1 (7.3 g, 23 mmol, 2.3 equiv) in dimethyl sulfoxide (40 mL) was added bis(pinacolato)diboron (2.5 g, 10 mmol, 1.0 equiv), Pd(dppf)Cl 2 (0.439 g, 0.6 mmol, 6.0 mol%), and K 2 CO 3 (8.8 g, 64 mmol, 6.4 equiv). After stirring the reaction mixture at 85 °C for 72 h under N 2 atmosphere, the reaction mixture was diluted with water and the aqueous layer was extracted with ethyl acetate (3 × 60 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, concentrated in vacuo, and the crude mixture was purified by flash column chromatography using hexane / ethyl acetate = 9:1 as the eluent to give 3.3 g (8.2 mmol, 82% yield) of the title compound as a white solid.

[0224] 1 H NMR(CDCl 3 , 400 MHz): δ 8.11 (d, J = 8.2 Hz, 4H), 7.48 (d, J = 8.2 Hz, 4H), 7.15 (s, 2H), 7.07 (s, 2H), 3.96 (s, 6H), 2.27 (s, 6H), 2.13 (s, 6H).

[0225] 13 C NMR (CDCl 3 , 100 MHz): δ 167.1, 146.7, 140.8, 139.6, 133.4, 132.1, 131.5, 131.0, 129.4, 129.3, 128.5, 52.1, 19.9, 19.4.

[0226] HRMS (ESI) calculated for C 32 H 30 O 4 [M + H] + requires m / z 479.2217, found m / z 479.2195.

[0227]

[0228] 2',2”,5',5”-Tetramethyl-[1,1':4',1”:4”,1”'-terphenyl]-4,4”'-dicarboxylic acid (L3). To a solution of S2 (2.8 g, 6.0 mmol, 10 equiv) in a mixed solvent of tetrahydrofuran (96 mL), methanol (24 mL), and water (24 mL), LiOH·H 2 O (2.5 g, 60 mmol, 10 equiv) was added. After stirring overnight at room temperature, the solution was acidified to pH ~ 5 with 1 M HCl. Then the solvent was removed. The resulting solid was collected by filtration, washed with water, and dried in vacuo to give 2.4 g (5.3 mmol, 89% yield) of the title compound as a white solid.

[0229] 1 H NMR (DMSO-d 6 , 400 MHz): δ 12.99 (brs, 2H), 8.03 (d, J = 8.2 Hz, 4H), 7.55 (d, J = 8.2 Hz, 4H), 7.20 (s, 2H), 7.08 (s, 2H), 2.25 (s, 6H), 2.08 (s, 6H).

[0230] 13 C NMR (DMSO-d 6 , 100 MHz): δ 167.2, 145.6, 140.3, 139.2, 132.8, 131.8, 131.3, 130.8, 129.3, 129.2, 19.6, 19.0.

[0231] HRMS (ESI) calculated for C 30 H 26 O 4 [M + H] +The required m / z is 451.1904, and the measured m / z is 451.1837.

[0232] Synthesis of copper complex:

[0233]

[0234] Cu-1. Under N 2 To a 50 mL Schlenk flask dried by direct fire, Cu(MeCN) 4 PF 6 (93 mg, 0.25 mmol), [1,1′-binaphthalene]-2,2′-diyl)bis(diphenylphosphine) (rac-binap) (156 mg, 0.25 mmol, 1.0 equiv) and dichloromethane (20 mL) were successively added. After stirring at room temperature for 1 hour, L1 (105 mg, 0.25 mmol, 1.0 equiv) in a mixed solvent of 15 mL dichloromethane and dimethylformamide (5:1 v / v) was added dropwise. Then, the whole solution was stirred overnight at room temperature. After the reaction was completed, dichloromethane was removed under vacuum. The residue was dropped into diethyl ether (80 mL), and the resulting yellow solid (229 mg, 0.183 mmol, 73% yield) was collected by filtration, washed several times with diethyl ether, and dried under vacuum.

[0235] 1 1H NMR (CDCl 3 , 400 MHz): δ 8.90 (s, 2H), 8.53 (s, 2H), 8.36 (s, 2H), 8.23 (d, J = 8.2 Hz, 4H), 7.63 (d, J = 8.2 Hz, 2H), 7.59 - 7.51 (m, 6H), 7.46 (t, J = 7.4 Hz, 2H), 7.36 - 7.11 (m, 14H), 7.08 - 7.00 (m, 4H), 6.92 (t, J = 7.4 Hz, 2H), 6.78 (d, J = 8.4 Hz, 2H), 6.70 (t, J = 7.4 Hz, 4H), 4.02 (s, 6H).

[0236] 31 31P NMR (CDCl 3 , 162 MHz): δ 1.7, -135.4 - -153.0 (m, 1P).

[0237] 13 13C NMR (CDCl 3 , 100 MHz): δ 166.6, 148.8, 142.2 (actual triplet, J PC = 1.6 Hz), 139.9, 139.8 (actual triplet, J PC= 10.0 Hz), 136.7, 135.9, 134.1 (actual triplet, J PC = 4.2 Hz), 133.9 (actual triplet, J PC = 9.2 Hz), 133.20, 133.15 (actual triplet, J PC = 8.2 Hz), 131.7 (actual triplet, J PC = 17.7 Hz), 130.7, 130.3 (actual triplet, J PC = 13.8 Hz), 130.0, 129.3 (actual triplet, J PC = 5.0 Hz), 129.1 (actual triplet, J PC = 2.9 Hz), 128.7, 128.3 (actual triplet, J PC = 16.5 Hz), 128.2, 127.7 (actual triplet, J PC = 5.3 Hz), 127.5, 127.4 (actual triplet, J PC = 3.5 Hz), 127.23 (actual triplet, J PC = 29.9 Hz), 127.21 52.5。

[0238] FT-IR (thin film): 2923, 1717, 1431, 1280, 1106, 838, 748, 558 cm -1 。

[0239] HRMS (ESI) calculated for [C 72 H 52 CuN 2 O 4 P 2 + requires m / z 1133.2693, found m / z 1133.2693。

[0240]

[0241] Cu-2. To N 2 while cooling, sequentially add Cu(MeCN) 4 PF 6 ​(93 mg, 0.25 mmol), dichloromethane (20 mL), and rac-binap (156 mg, 0.25 mmol, 1.0 equiv). After stirring at room temperature for 1 h, L2 (112 mg, 0.25 mmol, 1.0 equiv) in dichloromethane and dimethylformamide (5:1 v / v) was added dropwise. Then, the whole solution was stirred at room temperature overnight. After completion of the reaction, dichloromethane was removed under vacuum. The residue was added dropwise to diethyl ether (50 mL), and the resulting yellow solid (276 mg, 0.215 mmol, 86% yield) was collected by filtration, washed several times with diethyl ether, and dried under vacuum.

[0242] 1 H NMR (DMSO-d 6 , 400 MHz,): δ 13.2 (brs, 2H), 9.27 (s, 2H), 8.78 (s, 2H), 8.40 (s, 2H), 8.16 (d, J = 7.6 Hz, 4H), 7.85 - 7.66 (m, 8H), 7.49 - 7.06 (m, 20H), 6.91 (s, 2H), 6.76 - 6.65 (m, 6H).

[0243] 31 P NMR (DMSO-d 6 , 162 MHz): δ 2.3, -135.4 - -153.0 (m, 1P).

[0244] FT-IR (thin film): 2973, 1689, 1276, 1069, 838, 743, 693 cm -1 .

[0245] HRMS (ESI) calcd for [C 70 H 48 CuN 2 O 4 P 2 + requires m / z 1105.2380, found m / z 1105.2373.

[0246]

[0247] Cu-3. Under N 2 protection, Cu(MeCN) 4 PF 6 ​(93 mg, 0.25 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (xantphos) (146 mg, 0.25 mmol, 1.0 equiv), and dichloromethane (20 mL). After stirring at room temperature for 1 hour, L1 (105 mg, 0.25 mmol, 1.0 equiv) in a mixed solvent of 15 mL dichloromethane and dimethylformamide (2:1 v / v) was added dropwise. Then, the whole solution was stirred overnight at room temperature. After completion of the reaction, dichloromethane was removed under vacuum. The residue was added dropwise to diethyl ether (80 mL), and the resulting orange solid (216 mg, 0.18 mmol, 72% yield) was collected by filtration, washed several times with diethyl ether, and dried under vacuum.

[0248] 1 H NMR (DMSO-d 6 , 400 MHz,): δ 9.13 (s, 2H), 8.69 (s, 2H), 8.30 (s, 2H), 8.13 (d, J = 8.4 Hz, 4H), 7.91 (d, J = 7.2 Hz, 2H), 7.61 (d, J = 8.4 Hz, 4H), 7.28 (t, J = 7.6 Hz, 6H), 7.13 (t, J = 7.6 Hz, 8H), 7.04 - 6.91 (m, 8H), 6.64 - 6.54 (m, 2H), 3.93 (s, 6H), 1.70 (s, 6H).

[0249] 31 P NMR (DMSO-d 6 , 162 MHz): δ -11.4, -124.7 - 159.9 (m, 1P).

[0250] 13 C NMR (DMSO-d 6 , 100 MHz): δ 165.8, 154.5 (actual triplet, J PC = 6.4 Hz), 147.4, 141.7 (actual triplet, J PC = 1.8 Hz), 139.7, 135.9, 135.5, 134.0, 132.5 (actual triplet, J PC = 8.0 Hz), 131.0, 130.7 (actual triplet, J PC = 17.0 Hz), 130.1 (two carbon signals overlapping), 130.0, 129.4, 128.8 (actual triplet, J PC = 4.7 Hz), 128.2, 127.9, 127.7, 125.6, 119.1 (actual triplet, J PC = 13.6 Hz), 52.5, 36.0, 27.7.

[0251] FT-IR (thin film): 2933, 1708, 1231, 845, 746, 670 cm -1 。

[0252] HRMS (ESI) calculated for [C 67 H 52 CuN 2 O 5 P 2 + requires m / z 1089.2642, found m / z 1089.2258.

[0253]

[0254] Cu-4. In N 2 under N₂, to a 50 mL Schlenk flask dried by direct fire were successively added Cu(MeCN) 4 PF 6 (93 mg, 0.25 mmol), xantphos (146 mg, 0.25 mmol, 1.0 equiv) and dichloromethane (20 mL). After stirring at room temperature for 1 h, L2 (105 mg, 0.25 mmol, 1.0 equiv) in a mixed solvent of 15 mL dichloromethane and dimethylformamide (2:1 v / v) was added dropwise. Then, the whole solution was stirred at room temperature overnight. After completion of the reaction, dichloromethane was removed under vacuum. The residue was dropped into diethyl ether (80 mL), and the resulting orange solid (216 mg, 0.18 mmol, yield 72%) was collected by filtration, washed several times with diethyl ether and dried under vacuum.

[0255] 1 ¹H NMR (DMSO-d 6 , 400 MHz,): δ 13.2 (brs, 2H), 9.12 (s, 2H), 8.70 (s, 2H), 8.30 (s, 2H), 8.12 (d, J = 8.4 Hz, 4H), 7.89 (s, 2H), 7.60 (s, 2H), 7.42 - 6.83 (m, 24H), 6.58 (d, J = 6.9 Hz, 2H), 1.69 (s, 6H).

[0256] 31 ³¹P NMR (DMSO-d 6 , 162 MHz): δ -11.4, -135.4 - -153.0 (m, 1P).

[0257] FT-IR (thin film): 2985, 1705, 1226, 842, 743, 693 cm -1 。 ​

[0258] HRMS(ESI) calculation for [C 65 H 48 CuN 2 O 5 P 2 + The required m / z is 1061.2329, and the measured m / z is 1061.2329.

[0259] Preparation and characterization of UiO-69 MOF material:

[0260]

[0261] ZrCl 4 (179 mg, 0.77 mmol), 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid (L2) (50 mg, 0.12 mmol), terphenyl dicarboxylic acid (L3) (270 mg, 0.60 mmol) and trifluoroacetic acid (0.4 mL) were ultrasonically dispersed in dimethylformamide (34 mL). The resulting solution was heated to 100 °C in a 50 mL glass tube and maintained for 3 days. After cooling to room temperature, the supernatant was decanted and the solid was washed five times with dimethylformamide and acetone. Then UiO-69-phen was collected by filtration and dried in air to obtain a white solid (389 mg, 60% yield based on the linker). The product (2 mg) was digested in a saturated K 3 PO 4 / D 2 O solution and DMSO-d 6 (0.6 mL, 1:2 v / v) mixture for 1 H NMR analysis. The ratio of L2 and L3 was found to be 1:5. Based on the NMR digestion data and TGA, the chemical formula of UiO-69-phen was determined to be Zr 6 O 4 (OH) 4 (L2)(L3) 5 ·4.0 DMF.

[0262]

[0263] UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in a dichloromethane solution of 2-mL [Cu(MeCN) 4 (PF 6 )(10.4 mg, 28 μmol) under N 2 ​Stir at 60 °C for 4 h under an atmosphere. After cooling to room temperature, decant the supernatant and wash the solid five times with dimethylformamide and acetone. Then filter to collect UiO-69-phenCu, air-dry to obtain a green solid (22.7 mg, 93% yield). ICP-AES analysis shows that the Zr / Cu ratio is 6:1. The chemical formula of UiO-69-phenCu is determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(CH 3 CN) 2 PF 6}·4.4DMF according to ICP-AES and TGA.

[0264]

[0265] UiO-69-phen (30.0 mg, 5.6 μmol based on L2) was immersed in a 2-mL dichloromethane solution of [Cu(xantphos)(MeCN) 2 (PF 6 )(24.3 mg, 28 μmol), and stirred at room temperature for 9 h under an N 2 atmosphere. After post-synthetic metallation, decant the supernatant and wash the solid five times with DMF and acetone. Then collect UiO-69-phen(xantphos)Cu by filtration and dry in air to obtain a yellow solid (30.9 mg, 91% yield). ICP-AES analysis shows that the Zr / Cu ratio is 6:1. Dissolve the product (2 mg) in D 3 PO 4 / D 2 O / DMSO-d 6 (1:1:5 v / v / v) solution and perform 1 H NMR analysis. The ratio of Cu-3 to L3 was found to be 1:5. The chemical formula of UiO-69-phen(xantphos)Cu is determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(xantphos)PF 6}·4.9DMF according to NMR digestion data and TGA.

[0266]

[0267] UiO-69-phen (300 mg, 56 μmol based on L2) was immersed in 20-mL of [Cu(binap)(MeCN) 2 (PF6 (256 mg, 0.28 mmol) in dichloromethane was stirred at room temperature for 9 h under N 2 atmosphere. After synthesis and metallization, the supernatant was decanted, and the solid was washed five times with DMF and acetone. Then UiO-69-phen(binap)Cu was collected by filtration and dried in air to give a yellow solid (312 mg, 94% yield). ICP-AES analysis showed that the Zr / Cu ratio was 6:1. The product (2 mg) was dissolved in D 3 PO 4 / D 2 O / DMSO-d 6 (1:1:5 v / v / v) solution and 1 H NMR analysis was performed. The ratio of Cu-2 and L3 was found to be 1:5. Based on the NMR digestion data and TGA, the chemical formula of UiO-69-phen(binap)Cu was determined to be {Zr 6 O 4 (OH) 4 (L2)(L3) 5 [Cu(binap)PF 6}·6.0 DMF.

[0268] According to the TGA ( Figure 9 ), the molecular weight of the prepared UiO-69-phen(binap)Cu was determined to be 5926. In other words, 1.0 mmol of copper catalyst could be obtained from 5926 mg of UiO-69-phen(binap)Cu. If a catalytic reaction is to be carried out with a 0.2 mol% copper catalyst (0.2 mmol scale): amount of UiO-69-phen(binap)Cu = 5926 mg × 0.2 × 0.002 = 2.4 mg

[0269] Synthesis of exocyclic arylenes:

[0270]

[0271] 3-(Naphthalen-2-ylmethylene)oxetane. According to the method reported in the literature 2 , the title compound was synthesized using the corresponding phosphorus bromide (9.7 g, 20 mmol, 1.0 equiv), oxetan-3-one (1.4 mL, 24 mmol, 1.2 equiv), t BuOK (2.2 g, 20 mmol, 1.0 equiv) and tetrahydrofuran (200 mL). After the reaction was completed, the crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to give 2.7 g (13.6 mmol, 68% yield) of the title compound as a white solid.

[0272] 1 1H NMR (CDCl 3 , 400 MHz): δ 7.84 - 7.72 (m, 3H), 7.52 - 7.40 (m, 3H), 7.10 (dd, J = 8.6, 1.8 Hz, 1H), 6.31 - 6.20 (m, 1H), 5.72 - 5.63 (m, 2H), 5.48 - 5.39 (m, 2H).

[0273] 13 13C NMR (CDCl 3 , 100 MHz): δ 137.4, 133.50, 133.49, 132.2, 128.4, 127.9, 127.6, 126.4, 126.3, 126.0, 124.6, 119.8, 80.5, 80.3.

[0274] HRMS (EI) calcd for [C 14 12 12 H + 8O] requires m / z 196.0883, found m / z 196.0884.

[0275]

[0276] 3-([1,1'-Biphenyl]-4-ylmethylene)oxetane. According to the method reported in the literature 2 using the corresponding phosphonium bromide (1.2 g, 2.0 mmol, 1.0 equiv), oxetan-3-one (180 μL, 3.0 mmol, 1.5 equiv), t BuOK (0.224 g, 2.0 mmol, 1.0 equiv) and tetrahydrofuran (20 mL) to synthesize the title compound. After the reaction was completed, the crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to give 0.305 g (1.38 mmol, 69% yield) of the title compound as a white solid.

[0277] 1 1H NMR (CDCl 3 , 400 MHz): δ 7.62 - 7.53 (m, 4H), 7.47 - 7.40 (m, 2H), 7.37 - 7.31 (m, 1H), 7.07 (d, J = 8.4 Hz, 2H), 6.18 - 6.08 (m, 1H), 5.66 - 5.55 (m, 2H), 5.45 - 5.35 (m, 2H).

[0278] 13 13C NMR (CDCl 3, 100 MHz): δ 140.5, 139.6, 137.2, 135.0, 128.8, 127.5, 127.4, 126.9, 119.3, 80.40, 80.27.

[0279] HRMS (EI) calculation for [C 16 H 14 O] + requires m / z 222.1039, found m / z 222.1041.

[0280]

[0281] To a cooled to N 2 under 25 mL of a flame-dried Schlenk flask cooled, 3-(4-bromobenzylidene)oxetane (222 mg, 1.0 mmol, 1.0 equiv) was added to 4 mL of tetrahydrofuran (0.25 M). After cooling to -78 °C, a dropwise addition n BuLi (2.5 M in THF, 440 μL, 1.1 equiv). The resulting solution was stirred at -78 °C for 1 h, then dimethylacetamide (50 mmol, 4.6 mL) was added. The system was slowly warmed to room temperature and stirred for an additional 1 h at ambient temperature. Then the reaction was quenched with saturated NH 4 Cl aqueous solution, and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography using hexanes / ethyl acetate (7:1 v / v) as the eluent to afford 58 mg (0.31 mmol, 31% yield) of 1-(4-(oxetane-3-ylmethylene)phenyl)ethan-1-one as a colorless oil.

[0282] 1 H NMR (CDCl 3 , 400 MHz): δ 7.92 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.19 - 6.14 (m, 1H), 5.62 - 5.56 (m, 2H), 5.44 - 5.37 (m, 2H), 2.59 (s, 3H).

[0283] 13 C NMR (CDCl 3 , 100 MHz): δ 197.4, 140.8, 140.5, 135.3, 128.9, 127.1, 119.0, 80.3, 80.1, 26.5.

[0284] HRMS (EI) calculation for [C 12 H 12 O2 + The required m / z is 188.0832, and the measured m / z is 188.0835.

[0285]

[0286] To a 25 mL direct-fire dried Schlenk flask cooled under N 2 , 3-(4-bromobenzylidene)oxetane (222 mg, 1.0 mmol, 1.0 equiv) was added to 4 mL of tetrahydrofuran (0.25 M). After cooling to -78 °C, n BuLi (2.5 M in THF, 440 μL, 1.1 equiv) was added dropwise. The resulting solution was stirred at -78 °C for 1 h, and then dimethylformamide (50 mmol, 3.9 mL) was added. The system was slowly warmed to room temperature and stirred for another 1 h at ambient temperature. Then the reaction was quenched with saturated NH 4 Cl aqueous solution, and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography using hexane / ethyl acetate (7:1 v / v) as the eluent to give 89 mg (0.51 mmol, 51% yield) of 4-(oxetan-3-ylidene)benzaldehyde as a colorless oil.

[0287] 1 1H NMR (CDCl 3 , 400 MHz): δ 9.98 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 6.22 - 6.16 (m, 1H), 5.64 - 5.57 (m, 2H), 5.45 - 5.38 (m, 2H).

[0288] 13 13C NMR (CDCl 3 , 100 MHz): δ 191.5, 141.9, 141.7, 134.6, 130.2, 127.5, 119.0, 80.3, 80.1.

[0289] HRMS (EI) calculated for [C 11 H 10 O 2 + The required m / z is 174.0675, and the measured m / z is 174.0679.

[0290]

[0291] To a... under N 2 ​​In a downward-cooled 50 mL direct-fire dried Schlenk flask, phosphorus bromide (2.9 g, 6.0 mmol, 1.2 equiv) was added to 15 mL of tetrahydrofuran. After cooling to 0 °C, n BuLi (2.5 M in THF, 2.8 mL, 1.4 equiv) was added dropwise. The resulting solution was stirred at 0 °C for 1 hour, and then cyclohexanone (5.0 mmol, 518 μL, 1.0 equiv) in 5 mL of tetrahydrofuran was added dropwise. The system was warmed to room temperature and stirred at ambient temperature for an additional 18 hours. Then the reaction was quenched with saturated NH 4 Cl aqueous solution and extracted with ethyl acetate (3 × 40 mL). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by flash column chromatography using hexane as the eluent to give 0.697 g (3.15 mmol, 63% yield) of 2-(cyclohexylidene)naphthalene as a colorless oil.

[0292] 1 1H NMR (CDCl 3 , 400 MHz): δ 7.83 - 7.71 (m, 3H), 7.65 - 7.60 (m, 1H), 7.48 - 7.38 (m, 2H), 7.38 - 7.32 (m, 1H), 6.37 (s, 1H), 2.49 - 2.40 (m, 2H), 2.35 - 2.26 (m, 2H), 1.73 - 1.54 (m, 6H).

[0293] 13 13C NMR (CDCl 3 , 100 MHz): δ 144.0, 135.9, 133.4, 131.8, 127.8, 127.7, 127.5, 127.4, 127.1, 125.9, 125.3, 122.0, 37.7, 29.6, 28.6, 27.9, 26.7.

[0294] HRMS (EI) calculated for [C 17 14 18 H + requires m / z 222.1403, found m / z 222.1406.

[0295] Photoinduced intermolecular [2 + 2] cycloaddition:

[0296]

[0297] Methyl trans-2-(naphthalen-1-yl)cyclobutane-1-carboxylate (1). The title compound was synthesized according to General Method A using 1-vinylnaphthalene (30.7 mg, 0.2 mmol) and methyl acrylate (91 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 35.2 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0298] 1 H NMR(CDCl 3 , 400 MHz): δ 7.96 - 7.92 (m, 1H), 7.86 - 7.82 (m, 1H), 7.74 - 7.70 (m, 1H), 7.51 - 7.44 (m, 4H), 4.44 (q, J = 9.2 Hz, 1H), 3.69 (s, 3H), 3.57 - 3.48 (m, 1H), 2.63 - 2.52 (m, 1H), 2.49 - 2.38 (m, 1H), 2.27 - 2.07 (m, 2H).

[0299] 13 C NMR(CDCl 3 , 100 MHz): δ 174.9, 139.0, 133.7, 131.3, 128.7, 127.0, 125.8, 125.6, 125.4, 123.9, 122.6, 51.8, 43.1, 41.0, 27.0, 22.0.

[0300] HRMS(EI) calcd for [C 16 H 16 O 2 + requires m / z 240.1145, found m / z 240.1148.

[0301]

[0302] tert-Butyl trans-2-(naphthalen-1-yl)cyclobutane-1-carboxylate (2). The title compound was synthesized according to General Method A using 1-vinylnaphthalene (30.9 mg, 0.2 mmol) and tert-butyl acrylate (145 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 46.1 mg (0.164 mmol, 80% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0303] 1 H NMR(CDCl 3 ​, 400 MHz): δ 8.01 - 7.96 (m, 1H), 7.86 - 7.82 (m, 1H), 7.74 - 7.70 (m, 1H), 7.50 - 7.44 (m, 4H), 4.38 (q, J = 9.2 Hz, 1H), 3.43 - 3.33 (m, 1H), 2.58 - 2.49 (m, 1H), 2.42 - 2.32 (m, 1H), 2.25 - 2.06 (m, 2H), 1.44 (s, 9H).

[0304] 13 C NMR(CDCl 3 , 100 MHz): δ 173.9, 139.5, 133.7, 131.4, 128.6, 126.8, 125.7, 125.5, 125.4, 124.1, 122.7, 80.3, 44.8, 40.8, 28.1, 26.6, 21.9.

[0305] HRMS(EI) calculated for [C 19 H 22 O 2 + requires m / z 282.1614, found m / z 282.1624.

[0306]

[0307] trans - 2 - (Naphthalen - 1 - yl)cyclobutane - 1 - carboxylic acid benzyl ester (3). The title compound was synthesized using 1 - vinylnaphthalene (30.9 mg, 0.2 mmol) and benzyl acrylate (162 mg, 1.0 mmol) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 46.4 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0308] 1 H NMR(CDCl 3 , 400 MHz): δ 7.97 - 7.91 (m, 1H), 7.88 - 7.82 (m, 1H), 7.76 - 7.68 (m, 1H), 7.51 - 7.43 (m, 4H), 7.35 - 7.26 (m, 5H), 5.23 - 5.06 (m, 2H), 4.56 - 4.38 (m, 1H), 3.64 - 3.47 (m, 1H), 2.65 - 2.39 (m, 2H), 2.29 - 2.10 (m, 2H).

[0309] 13 C NMR(CDCl 3 ​, 100 MHz): δ 174.3, 139.0, 136.0, 133.7, 131.3, 128.7, 128.5, 128.1, 128.0, 127.0, 125.8, 125.6, 125.4, 123.9, 122.7, 66.3, 43.5, 40.9, 26.9, 22.0.

[0310] HRMS(EI) calculation for [C 22 H 20 O 2 + Requires m / z 316.1458, found m / z 316.1467.

[0311]

[0312] Trans-3,3,3-trifluoro-2-(trifluoromethyl)propyl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (4). The title compound was synthesized according to General Method A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and 1,1,1,3,3,3-hexafluoropropan-2-yl acrylate (222 mg, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 45.0 mg (0.120 mmol, 60% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0313] 1 H NMR(CDCl 3 , 400 MHz): δ 7.94 - 7.83 (m, 2H), 7.75 (d, J = 8.0 Hz, 1H), 7.53 - 7.44 (m, 3H), 7.43 - 7.38 (m, 1H), 5.90 - 5.72 (m, 1H), 4.52 (q, J = 9.2 Hz, 1H), 3.77 - 3.64 (m, 1H), 2.75 - 2.61 (m, 1H), 2.54 - 2.32 (m, 2H), 2.29 - 2.16 (m, 1H).

[0314] 19 F NMR(376 MHz, CDCl 3 ): δ -73.3.

[0315] 13 C NMR(CDCl 3 ​, 100 MHz): δ 171.1, 138.0, 133.8, 131.0, 128.8, 127.4, 126.0, 125.8, 125.4, 123.6, 122.5, 120.4 (q, J = 272.2 Hz), 66.6 (p, J = 34.7 Hz), 42.2, 40.7, 27.1, 22.2.

[0316] HRMS (EI) calculation for [C 18 H 14 F 6 O 2 + Calculated for m / z 376.0893, found m / z 376.0893.

[0317]

[0318] trans-Prop-2-yn-1-yl 2-(naphthalen-1-yl)cyclobutane-1-carboxylate (5). The title compound was synthesized using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and prop-2-yn-1-yl acrylate (110 mg, 1.0 mmol) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 38.1 mg (0.144 mmol, 72% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0319] 1 H NMR (CDCl 3 , 400 MHz): δ 7.98 - 7.91 (m, 1H), 7.87 - 7.82 (m, 1H), 7.76 - 7.70 (m, 1H), 7.52 - 7.42 (m, 4H), 4.70 (qd, J = 15.6, 2.4 Hz, 2H), 4.48 (q, J = 9.2 Hz, 1H), 3.63 - 3.49 (m, 1H), 2.65 - 2.54 (m, 1H), 2.51 - 2.38 (m, 2H), 2.31 - 2.10 (m, 2H).

[0320] 13 C NMR (CDCl 3 , 100 MHz): δ 173.6, 138.8, 133.8, 131.2, 128.7, 127.0, 125.9, 125.6, 125.4, 123.8, 122.6, 77.7, 74.9, 52.1, 43.0, 40.8, 27.0, 22.0.

[0321] HRMS (EI) calculation for [C 18 H​16 O 2 + The required m / z is 264.1145, and the measured m / z is 264.1153.

[0322]

[0323] Trans-N,N-dimethyl-2-(naphthalen-1-yl)cyclobutane-1-carboxamide (6). The title compound was synthesized using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and N,N-dimethylacrylamide (110 μL, 1.0 mmol) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (3:1 v / v) as the eluent to give 37.0 mg (0.146 mmol, 73% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0324] 1 H NMR (CDCl 3 , 400 MHz): δ 8.11 - 8.05 (m, 1H), 7.86 - 7.80 (m, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.52 - 7.38 (m, 4H), 4.70 - 4.57 (m, 1H), 3.59 - 3.47 (m, 1H), 2.94 (s, 3H), 2.76 (s, 3H), 2.54 - 2.45 (m, 1H), 2.41 - 2.17 (m, 3H).

[0325] 13 C NMR (CDCl 3 , 100 MHz): δ 173.6, 140.1, 133.8, 131.5, 128.5, 126.8, 125.7, 125.6, 125.4, 124.2, 122.6, 43.7, 39.2, 36.7, 35.6, 25.3, 22.3.

[0326] HRMS (EI) calculated for [C 17 H 19 NO] + The required m / z is 253.1461, and the measured m / z is 253.1471.

[0327]

[0328] ​1-(2-(Naphthalen-1-yl)cyclobutyl)propan-1-one (7). The title compound was synthesized using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and pent-1-en-3-one (89 μL, 1.0 mmol) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (15:1 v / v) as the eluent to give 31.9 mg (0.134 mmol, 67% yield, 6.0:1 d.r.) of the title compound as a colorless oil.

[0329] 1 H NMR(CDCl 3 , 400 MHz): δ 8.01 - 7.91 (m, 1H), 7.89 - 7.81 (m, 1H), 7.76 - 7.70 (m, 1H), 7.52 - 7.42 (m, 4H), 4.48 - 4.35 (m, 1H), 3.69 - 3.57 (m, 1H), 2.53 - 2.29 (m, 4H), 2.23 - 2.10 (m, 2H), 1.03 (t, J = 7.2 Hz, 3H).

[0330] 13 C NMR(CDCl 3 , 100 MHz): δ 211.7, 139.5, 133.8, 131.3, 128.7, 126.9, 125.9, 125.7, 125.4, 123.8, 122.5, 50.4, 39.5, 34.6, 26.1, 21.5, 7.6.

[0331] HRMS(EI) calcd for [C 17 H 18 O] + requires m / z 238.1352, found m / z 238.1354.

[0332]

[0333] Dimethyl 3-(naphthalen-1-yl)cyclobutane-1,2-dicarboxylate (8). The title compound was synthesized using 1-vinylnaphthalene (30.8 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to give 52.0 mg (0.174 mmol, 87% yield, 2.0:1 d.r.) of the title compound as a colorless oil.

[0334] 1¹H NMR(CDCl 3 , 400 MHz): δ 7.98 (d, J = 8.4 Hz, 0.34H), 7.91 - 7.81 (m, 1.66H), 7.77 - 7.71 (m, 1H), 7.55 - 7.42 (m, 4H), 4.83 (q, J = 9.2 Hz, 0.34H), 4.31 (q, J = 9.6 Hz, 0.66H), 4.13 - 3.95 (m, 0.34H), 3.84 - 3.76 (m, 1.68H), 3.75 - 3.62 (m, 4.30H), 3.60 - 3.49 (m, 0.66H), 3.16 - 3.06 (m, 0.34H), 2.93 - 2.83 (m, 1.68H), 2.73 - 2.64 (m, 0.34H), 2.33 (q, J = 10.4 Hz, 0.66H).

[0335] 13 ¹³C NMR(CDCl 3 , 100 MHz): δ 174.8, 173.5, 173.2, 171.7, 137.5, 134.9, 133.7, 133.5, 131.6, 131.2, 128.8, 128.5, 127.6, 127.4, 126.0, 125.7, 125.6, 125.5, 125.2, 123.7, 123.5, 123.4, 123.0, 52.17, 52.14, 52.07, 51.0, 47.3, 45.7, 37.3, 37.1, 36.7, 36.5, 30.7, 26.5.

[0336] HRMS (EI) calculated for [C 18 H 18 O 4 + requires m / z 298.1200, found m / z 298.1202.

[0337]

[0338] Dimethyl 3-(naphthalen - 2 - yl) cyclobutane - 1,2 - dicarboxylate (9). The title compound was synthesized according to General Method A using 2 - vinylnaphthalene (30.9 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO - 69 - phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 48.9 mg (0.164 mmol, 82% yield, 1.5:1 d.r.) of the title compound as a colorless oil.​

[0339] 1 H NMR(CDCl 3 , 400 MHz): δ 7.86 - 7.73 (m, 3H), 7.71 - 7.64 (m, 1H), 7.51 - 7.38 (m, 2.60H), 7.33 (dd, J=8.4, 1.6 Hz, 0.40H), 4.21 - 4.08 (m, 0.40H), 3.98 - 3.86 (m, 0.40H), 3.84 - 3.68 (m, 5.80H), 3.65 - 3.57 (m, 0.60H), 3.51 - 3.40 (m, 0.60H), 3.19 (s, 1.20H), 2.90 - 2.79 (m, 0.40H), 2.77 - 2.63 (m, 1H), 2.50 - 2.38 (m, 0.60H).

[0340] 13 C NMR(CDCl 3 , 100 MHz): δ 174.6, 173.6, 173.1, 171.6, 139.5, 137.3, 133.3, 133.2, 132.4, 128.3, 127.82, 127.78, 127.7, 127.6, 127.5, 126.2, 126.0, 125.8, 125.74, 125.66, 125.0, 124.9, 52.08, 52.05, 51.4, 47.5, 46.5, 40.0, 39.8, 36.8, 36.6, 29.4, 27.7.

[0341] HRMS(EI) calculated for [C 18 H 18 O 4 + requires m / z 298.1200, found m / z 298.1208.

[0342]

[0343] Dimethyl 3-(phenanthren-9-yl)cyclobutane-1,2-dicarboxylate (10). The title compound was synthesized according to General Method A using 9-vinylphenanthrene (40.8 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to afford 45.3 mg (0.130 mmol, 65% yield, 1.5:1 d.r.) of the title compound as a colorless oil. ​

[0344] 1 H NMR(CDCl 3 , 400 MHz): δ 8.76 - 8.67 (m, 1H), 8.67 - 8.60 (m, 1H), 8.05 - 7.98 (m, 0.40H), 7.94 - 7.85 (m, 1.60H), 7.73 (s, 0.60H), 7.69 - 7.54 (m, 4.40H), 4.92 - 4.73 (m, 0.40H), 4.37 - 4.25 (m, 0.60H), 4.11 - 4.04 (m, 0.40H), 3.96 - 3.88 (m, 0.60H), 3.82 (s, 1.20H), 3.76 - 3.71 (m, 3.60H), 3.70 - 3.65 (m, 0.40H), 3.64 - 3.55 (m, 0.60H), 3.31 - 3.19 (m, 0.40H), 2.97 - 2.88 (m, 0.60H), 2.86 (s, 1.20H), 2.77 - 2.67 (m, 0.40H), 2.41 - 2.27 (m, 0.60H).

[0345] 13 C NMR(CDCl 3 , 100 MHz): δ 174.8, 173.5, 173.3, 171.7, 135.7, 133.1, 131.5, 131.3, 130.7, 130.4, 130.3, 129.8, 129.7, 129.5, 128.7, 128.6, 126.8, 126.7, 126.60, 126.57, 126.55, 126.5, 126.34, 126.31, 124.7, 124.5, 124.1, 123.9, 123.3, 122.9, 122.39, 122.36, 52.21, 52.19, 52.1, 51.0, 47.4, 45.2, 37.6, 37.2, 37.1, 36.81, 30.78, 26.3.

[0346] HRMS(EI) calculated for [C 22 H 20 O 4 + requires m / z 348.1356, found m / z 348.1365.

[0347]

[0348] ​Dimethyl 3-([1,1'-biphenyl]-4-yl)cyclobutane-1,2-dicarboxylate (11). The title compound was synthesized according to General Method A using 4-vinyl-1,1'-biphenyl (36.0 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 51.9 mg (0.160 mmol, 80% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0349] 1 H NMR(CDCl 3 , 400 MHz): δ 7.61 - 7.52 (m, 4H), 7.46 - 7.40 (m, 2H), 7.38 - 7.27 (m, 3H), 4.08 - 3.97 (m, 0.40H), 3.92 - 3.84 (m, 0.40H), 3.79 - 3.71 (m, 5.20H), 3.70 - 3.63 (m, 0.60H), 3.58 - 3.50 (m, 0.60H), 3.47 - 3.37 (m, 0.60H), 3.29 (s, 1.20H), 2.79 - 2.59 (m, 1.40H), 2.43 - 2.31 (m, 0.60H).

[0350] 13 C NMR(CDCl 3 , 100 MHz): δ 174.6, 173.6, 173.1, 171.6, 141.2, 140.8, 140.6, 139.8, 139.7, 138.9, 128.7, 127.8, 127.24, 127.21, 127.02, 127.00, 126.91, 126.88, 52.09, 52.06, 51.4, 47.6, 46.5, 39.6, 39.4, 36.8, 36.6, 29.4, 27.8.

[0351] HRMS(EI) calcd for [C 20 H 20 O 4 + requires m / z 324.1356, found m / z 324.1365.

[0352]

[0353] ​Dimethyl 3-(4-formylphenyl)cyclobutane-1,2-dicarboxylate (12). The title compound was synthesized according to General Method A using 4-vinylbenzaldehyde (26.4 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 28.2 mg (0.102 mmol, 51% yield, 1.9:1 d.r.) of the title compound as a colorless oil.

[0354] 1 H NMR(CDCl 3 , 400 MHz): δ 10.00 (s, 0.65H), 9.99 (s, 0.35H), 7.91 - 7.78 (m, 2H), 7.50 - 7.42 (m, 1.35H), 7.39 (d, J = 8.0 Hz, 0.65H), 4.14 - 4.03 (m, 0.35H), 3.95 - 3.86 (m, 0.35H), 3.80 - 3.69 (m, 5.95H), 3.57 - 3.38 (m, 1.30H), 3.28 (s, 1.05H), 2.80 - 2.59 (m, 1.35H), 2.41 - 2.30 (m, 0.65H).

[0355] 13 C NMR(CDCl 3 , 100 MHz): δ 191.84, 191.83, 174.2, 173.4, 172.7, 171.2, 149.1, 147.1, 135.1, 130.1, 129.7, 128.0, 127.2, 127.1, 52.24, 52.20, 52.17, 51.5, 47.2, 46.4, 39.9, 39.5, 36.8, 36.6, 29.0, 27.5.

[0356] HRMS(EI) calcd for [C 15 H 16 O 5 + requires m / z 276.0992, found m / z 276.1003.

[0357]

[0358] ​Dimethyl 3-(4-acetylphenyl)cyclobutane-1,2-dicarboxylate (13). The title compound was synthesized according to General Method A using 1-(4-vinylphenyl)ethan-1-one (32.4 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (20:1 v / v) as the eluent to give 31.9 mg (0.110 mmol, 55% yield, 1.9:1 d.r.) of the title compound as a colorless oil.

[0359] 1 H NMR(CDCl 3 , 400 MHz): δ 7.96 - 7.87 (m, 2H), 7.40 - 7.34 (m, 1.34H), 7.32 (d, J = 8.3 Hz, 0.66H), 4.11 - 3.99 (m, 0.34H), 3.97 - 3.84 (m, 0.34H), 3.78 - 3.66 (m, 5.66H), 3.56 - 3.38 (m, 1.32H), 3.29 (s, 1.02H), 2.78 - 2.55 (m, 4.66H), 2.41 - 2.29 (m, 0.66H).

[0360] 13 C NMR(CDCl 3 , 100 MHz): δ 197.71, 197.68, 174.3, 173.4, 172.8, 171.3, 147.5, 145.5, 135.8, 128.7, 128.4, 127.6, 126.8, 126.6, 52.20, 52.17, 52.1, 51.5, 47.3, 46.3, 39.7, 39.4, 36.8, 36.6, 29.1, 27.5, 26.60, 26.58.

[0361] HRMS(EI) calcd for [C 16 H 18 O 5 + requires m / z 290.1149, found m / z 290.1156.

[0362]

[0363] ​Dimethyl 3-(quinolin-6-yl)cyclobutane-1,2-dicarboxylate (14). The title compound was synthesized according to General Method A using 6-vinylquinoline (31.1 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (6:1 → 3:1 v / v) as the eluent to give 31.7 mg (0.106 mmol, 53% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0364] 1 H NMR(CDCl 3 , 400 MHz): δ 8.96 - 8.83 (m, 1H), 8.17 - 8.11 (m, 1H), 8.08 (d, J = 8.7 Hz, 0.55H), 8.04 (d, J = 8.7 Hz, 0.45H), 7.71 - 7.64 (m, 1.55H), 7.57 (dd, J = 8.7, 2.1 Hz, 0.45H), 7.45 - 7.37 (m, 1H), 4.25 - 4.15 (m, 0.45H), 4.00 - 3.90 (m, 0.45H), 3.88 - 3.72 (m, 5.65H), 3.65 - 3.58 (m, 0.55H), 3.50 - 3.42 (m, 0.55H), 3.20 (s, 1.35H), 2.92 - 2.81 (m, 0.45H), 2.78 - 2.68 (m, 1H), 2.49 - 2.40 (m, 0.55H).

[0365] 13 C NMR(CDCl 3 , 100 MHz): δ 174.4, 173.5, 172.9, 171.5, 150.24, 150.17, 147.4, 140.4, 138.3, 136.0, 135.9, 129.74, 129.68, 129.3, 128.6, 128.1, 128.0, 125.5, 124.8, 124.5, 121.4, 121.3, 52.18, 52.16, 52.1, 51.5, 47.5, 46.5, 39.8, 39.5, 36.8, 36.6, 29.3, 27.6.

[0366] HRMS(EI) calcd for [C 17 H 17 NO 4 + requires m / z 299.1152, found m / z 299.1155.​

[0367]

[0368] Dimethyl 3-(isoquinolin-6-yl)cyclobutane-1,2-dicarboxylate (15). The title compound was synthesized according to General Method A using 6-vinylisoquinoline (31.1 mg, 0.2 mmol), dimethyl fumarate (34.6 mg, 0.24 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (6:1 → 3:1 v / v) as the eluent to give 29.9 mg (0.100 mmol, 50% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0369] 1 H NMR(CDCl 3 , 400 MHz): δ 8.95 - 8.81 (m, 1H), 8.19 - 8.01 (m, 2H), 7.72 - 7.63 (m, 1.60H), 7.57 (dd, J = 8.8, 2.1 Hz, 0.40H), 7.45 - 7.35 (m, 1H), 4.26 - 4.14 (m, 0.40H), 4.01 - 3.90 (m, 0.40H), 3.88 - 3.72 (m, 5.80H), 3.65 - 3.58 (m, 0.60H), 3.52 - 3.42 (m, 0.60H), 3.20 (s, 1.20H), 2.89 - 2.81 (m, 0.40H), 2.78 - 2.66 (m, 1H), 2.51 - 2.38 (m, 0.60H).

[0370] 13 C NMR(CDCl 3 , 100 MHz): δ 174.4, 173.5, 172.9, 171.5, 150.3, 150.2, 147.4, 140.4, 138.2, 136.0, 135.9, 129.73, 129.68, 129.3, 128.6, 128.1, 128.0, 125.5, 124.8, 121.4, 121.3, 52.19, 52.16, 52.1, 51.5, 47.5, 46.5, 39.8, 39.5, 36.8, 36.6, 29.3, 27.6.

[0371] HRMS(EI) calcd for [C 17 H 17 NO 4 + ​The required m / z is 299.1152, and the measured m / z is 299.1153.

[0372]

[0373] 2-Phenylcyclobutanecarbonitrile (16). The title compound was synthesized according to General Method A using styrene (41.6 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol%), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to afford 41.5 mg (0.264 mmol, 66% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0374] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.39 - 7.31 (m, 2H), 7.30 - 7.19 (m, 3H), 3.96 - 3.78 (m, 1H), 3.13 - 3.01 (m, 1H), 2.45 - 2.21 (m, 4H).

[0375] 13 C NMR (CDCl 3 , 100 MHz): δ 141.2, 128.7, 127.2, 126.0, 121.3, 45.0, 29.2, 26.5, 23.1.

[0376] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 7.43 - 7.34 (m, 2H), 7.33 - 7.24 (m, 3H), 3.95 - 3.84 (m, 1H), 3.56 - 3.46 (m, 1H), 2.75 - 2.60 (m, 1H), 2.55 - 2.35 (m, 2H), 2.34 - 2.25 (m, 1H).

[0377] 13 C NMR (CDCl 3 , 100 MHz): δ 139.2, 128.6, 127.4, 127.1, 120.8, 41.7, 30.7, 25.7, 23.2.

[0378] HRMS (EI) calcd for [C 11 H 11 N]+ The required m / z is 157.0886, and the measured m / z is 157.0870.

[0379]

[0380] 2-(4-Methoxyphenyl)cyclobutane-1-carbonitrile (17). The title compound was synthesized according to General Method A using 1-methoxy-4-vinylbenzene (53.7 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol%) and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to give 48.7 mg (0.260 mmol, 65% yield, 1.2:1 d.r.) of the title compound as a colorless oil.

[0381] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.16 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 3.85 - 3.73 (m, 4H), 3.07 - 2.94 (m, 1H), 2.40 - 2.17 (m, 4H).

[0382] 13 C NMR (CDCl 3 , 100 MHz): δ 158.7, 133.3, 127.2, 121.4, 114.0, 55.3, 44.6, 29.6, 26.8, 23.0.

[0383] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 7.23 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.6 Hz, 2H), 3.88 - 3.77 (m, 4H), 3.52 - 3.41 (m, 1H), 2.69 - 2.57 (m, 1H), 2.50 - 2.32 (m, 2H), 2.30 - 2.22 (m, 1H).

[0384] 13 C NMR (CDCl 3 , 100 MHz): δ 158.8, 131.4, 128.3, 121.0, 113.9, 55.2, 41.2, 30.9, 26.0, 23.0.

[0385] HRMS(EI) calculation for [C 12 H 13 NO] + Requires m / z 187.0992, measured m / z 187.0980.

[0386]

[0387] 2-(p-Tolyl)cyclobutane-1-carbonitrile (18). The title compound was synthesized according to General Method A using 1-methyl-4-vinylbenzene (47.3 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol%) and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to give 41.0 mg (0.240 mmol, 60% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0388] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.19 - 7.10 (m, 4H), 3.89 - 3.75 (m, 1H), 3.09 - 2.98 (m, 1H), 2.42 - 2.22 (m, 7H).

[0389] 13 C NMR(CDCl 3 , 100 MHz): δ 138.3, 136.9, 129.3, 125.9, 121.4, 44.8, 29.4, 26.6, 23.1, 21.0.

[0390] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.18 (s, 4H), 3.93 - 3.78 (m, 1H), 3.55 - 3.41 (m, 1H), 2.71 - 2.59 (m, 1H), 2.52 - 2.24 (m, 6H).

[0391] 13 C NMR(CDCl 3 , 100 MHz): δ 137.0, 136.2, 129.2, 127.0, 120.9, 41.5, 30.8, 25.8, 23.1, 21.1.

[0392] HRMS(EI) calculation for [C 12H 13 N] + The required m / z is 171.1043, and the measured m / z is 171.1039.

[0393]

[0394] 2-([1,1'-Biphenyl]-4-yl)cyclobutane-1-carbonitrile (19). The title compound was synthesized according to General Method A using 4-vinyl-1,1'-biphenyl (36.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to give 24.7 mg (0.106 mmol, 53% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0395] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.60 - 7.54 (m, 4H), 7.48 - 7.40 (m, 2H), 7.38 - 7.28 (m, 3H), 3.98 - 3.82 (m, 1H), 3.18 - 3.03 (m, 1H), 2.49 - 2.22 (m, 4H).

[0396] 13 C NMR (CDCl 3 , 100 MHz): δ 140.6, 140.2, 128.8, 127.39, 127.36, 127.0, 126.5, 121.3, 44.8, 29.3, 26.6, 23.2.

[0397] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 7.65 - 7.55 (m, 4H), 7.48 - 7.40 (m, 2H), 7.39 - 7.29 (m, 3H), 4.03 - 3.84 (m, 1H), 3.61 - 3.38 (m, 1H), 2.79 - 2.62 (m, 1H), 2.56 - 2.37 (m, 2H), 2.36 - 2.26 (m, 1H).

[0398] 13 C NMR (CDCl 3 , 100 MHz): δ 140.7, 140.2, 138.3, 128.7, 127.6, 127.3, 127.2, 127.1, 120.8, 41.5, 30.7, 25.8, 23.2.

[0399] HRMS(EI) calculation for [C 17 H 15 N] + Calculated m / z 233.1199, found m / z 233.1206.

[0400]

[0401] Methyl 4-(2-cyanocyclobutyl)benzoate (20). The title compound was synthesized according to General Method A using methyl 4-vinylbenzoate (32.4 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to afford 20.7 mg (0.096 mmol, 48% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0402] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 8.02 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 3.98 - 3.86 (m, 4H), 3.16 - 3.06 (m, 1H), 2.48 - 2.22 (m, 4H).

[0403] 13 C NMR (CDCl 3 , 100 MHz): δ 166.7, 146.2, 130.0, 129.1, 126.0, 121.0, 52.2, 44.7, 29.0, 26.3, 23.2.

[0404] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 8.06 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 4.01 - 3.88 (m, 4H), 3.60 - 3.51 (m, 1H), 2.75 - 2.64 (m, 1H), 2.58 - 2.40 (m, 2H), 2.36 - 2.27 (m, 1H).

[0405] 13 C NMR (CDCl 3 , 100 MHz): δ 166.8, 144.4, 129.9, 129.2, 127.1, 120.4, 52.1, 41.5, 30.5, 25.5, 23.2.

[0406] HRMS(EI) calculation for [C 13 H 13NO 2 + The required m / z is 215.0941, and the measured m / z is 215.0938.

[0407]

[0408] 2-(4-(Trifluoromethyl)phenyl)cyclobutane-1-carbonitrile (21). The title compound was synthesized according to General Method A using 1-(trifluoromethyl)-4-vinylbenzene (68.9 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to give 52.2 mg (0.232 mmol, 58% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0409] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.61 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 3.99 - 3.89 (m, 1H), 3.14 - 3.04 (m, 1H), 2.49 - 2.22 (m, 4H).

[0410] 19 F NMR(CDCl 3 , 376 MHz): δ -62.5.

[0411] 13 C NMR(CDCl 3 , 100 MHz): δ 145.1, 129.6 (q, J = 33.0 Hz), 126.4, 125.7 (q, J = 3.8 Hz), 124.0 (q, J = 270.0 Hz), 120.8, 44.5, 29.0, 26.3, 23.2.

[0412] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.64 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 4.01 - 3.90 (m, 1H), 3.61 - 3.51 (m, 1H), 2.75 - 2.63 (m, 1H), 2.58 - 2.42 (m, 2H), 2.36 - 2.28 (m, 1H). ​

[0413] 19 F NMR (CDCl 3 , 376 MHz): δ -62.5。

[0414] 13 C NMR (CDCl 3 , 100 MHz): δ 143.2, 129.6 (q, J=32.4 Hz), 127.5, 125.6 (q, J=3.8 Hz), 124.1 (q, J=270.0 Hz), 120.4, 41.3, 30.5, 25.6, 23.2。

[0415] HRMS (EI) calculated for [C 12 H 10 F 3 N] + requires m / z 225.0760, found m / z 225.0762。

[0416]

[0417] 2-(4-Chlorophenyl)cyclobutane-1-carbonitrile (22). The title compound was synthesized according to General Procedure A using 1-chloro-4-vinylbenzene (55.4 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol%) and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to afford 49.7 mg (0.260 mmol, 65% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0418] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.32 (d, J=8.4 Hz, 2H), 7.16 (d, J=8.4 Hz, 2H), 3.90 - 3.76 (m, 1H), 3.08 - 2.97 (m, 1H), 2.44 - 2.15 (m, 4H).

[0419] 13 C NMR (CDCl 3 , 100 MHz): δ 139.6, 133.0, 128.8, 127.4, 121.0, 44.4, 29.2, 26.5, 23.1.

[0420] Minor: 1¹H NMR(CDCl 3 , 400 MHz): δ 7.35 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 3.92 - 3.80 (m, 1H), 3.56 - 3.44 (m, 1H), 2.70 - 2.58 (m, 1H), 2.54 - 2.36 (m, 2H), 2.33 - 2.24 (m, 1H).

[0421] 13 ¹³C NMR(CDCl 3 , 100 MHz): δ 137.7, 133.2, 128.7, 128.5, 120.6, 41.1, 30.6, 25.7, 23.0.

[0422] HRMS(EI) calcd for [C 11 H 10 ClN] + requires m / z 191.0496, found m / z 191.0501.

[0423]

[0424] 2-(Naphthalen-1-yl)cyclobutane-1-carbonitrile (23). The title compound was synthesized according to General Procedure A using 1-vinylnaphthalene (30.8 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to give 28.1 mg (0.136 mmol, 68% yield, 1.6:1 d.r.) of the title compound as a colorless oil.

[0425] 1 ¹H NMR(CDCl 3 , 400 MHz): δ 8.01 (d, J = 8.8 Hz, 0.62H), 7.91 - 7.85 (m, 1H), 7.85 - 7.74 (m, 1.38H), 7.59 - 7.41 (m, 3.38H), 7.35 (d, J = 7.2 Hz, 0.62H), 4.67 - 4.48 (m, 1H), 3.84 - 3.70 (m, 0.38H), 3.38 - 3.27 (m, 0.62H), 3.11 - 2.93 (m, 0.38H), 2.66 - 2.26 (m, 3.62H).

[0426] 13 ¹³C NMR(CDCl 3, 100 MHz): δ 136.8, 134.5, 133.8, 133.7, 131.02, 130.96, 129.1, 128.8, 128.1, 127.8, 126.4, 126.3, 126.0, 125.7, 125.34, 125.26, 124.4, 123.5, 122.6, 122.5, 121.4, 120.5, 42.5, 39.3, 31.9, 27.6, 27.2, 24.2, 23.4, 23.3.

[0427] HRMS (EI) calculation [C 15 H 13 N] + requires m / z 207.1043, found m / z 207.1046.

[0428]

[0429] 2-(4-Fluoronaphthalen-1-yl)cyclobutane-1-carbonitrile (24). The title compound was synthesized using 1-fluoro-4-vinylnaphthalene (34.5 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol) according to General Method A. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (12:1 v / v) as the eluent to give 33.7 mg (0.150 mmol, 75% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0430] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 8.20 - 8.11 (m, 1H), 8.06 - 7.96 (m, 1H), 7.69 - 7.54 (m, 2H), 7.30 - 7.24 (m, 1H), 7.18 - 7.06 (m, 1H), 4.57 - 4.39 (m, 1H), 3.35 - 3.16 (m, 1H), 2.67 - 2.27 (m, 4H).

[0431] 19 F NMR (376 MHz, CDCl 3 ): δ -123.9.

[0432] 13 C NMR (CDCl 3, 100 MHz): δ 158.2 (d, J = 252.0 Hz), 132.7 (d, J = 4.4 Hz), 132.2 (d, J = 4.4 Hz), 127.4, 126.3 (d, J = 1.9 Hz), 124.0 (d, J = 16.3 Hz), 123.6 (d, J = 2.8 Hz), 122.4 (d, J = 8.7 Hz), 121.32 (d, J = 4.8 Hz), 121.31, 108.6 (d, J = 20.0 Hz), 42.1, 27.9, 27.1, 23.4.

[0433] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 8.21 - 8.13 (m, 1H), 7.83 - 7.75 (m, 1H), 7.63 - 7.53 (m, 2H), 7.45 - 7.37 (m, 1H), 7.22 - 7.12 (m, 1H), 4.56 - 4.38 (m, 1H), 3.85 - 3.62 (m, 1H), 3.10 - 2.89 (m, 1H), 2.68 - 2.53 (m, 1H), 2.51 - 2.39 (m, 1H), 2.37 - 2.22 (m, 1H).

[0434] 19 F NMR (376 MHz, CDCl 3 ): δ -123.59.

[0435] 13 C NMR (CDCl 3 , 100 MHz): δ 158.4 (d, J = 252.3 Hz), 132.3 (d, J = 4.4 Hz), 130.4 (d, J = 4.3 Hz), 127.3, 126.1 (d, J = 1.9 Hz), 124.4 (d, J = 8.7 Hz), 124.0 (d, J = 16.4 Hz), 122.7 (d, J = 2.9 Hz), 121.7 (d, J = 5.8 Hz), 120.4, 108.8 (d, J = 20.1 Hz), 39.0, 31.9, 24.3, 23.3.

[0436] HRMS (EI) calculated [C 15 H 12 F N] + requires m / z 225.0948, found m / z 225.0958.

[0437]

[0438] 2-(Phenanthren-9-yl)cyclobutane-1-carbonitrile (25). The title compound was synthesized according to General Method A using 9-vinylphenanthrene (40.9 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 v / v) as the eluent to afford 38.6 mg (0.150 mmol, 75% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0439] 1 H NMR(CDCl 3 , 400 MHz): δ 8.78 - 8.70 (m, 1H), 8.65 (d, J = 8.1 Hz, 1H), 8.07 - 8.00 (m, 0.56H), 7.95 - 7.85 (m, 1H), 7.83 - 7.77 (m, 0.44H), 7.72 - 7.55 (m, 5H), 4.59 - 4.43 (m, 1H), 3.86 - 3.76 (m, 0.44H), 3.45 - 3.36 (m, 0.56H), 3.24 - 2.99 (m, 0.56H), 2.72 - 2.30 (m, 3.44H).

[0440] 13 C NMR(CDCl 3 , 100 MHz): δ 135.2, 132.8, 131.4, 131.2, 130.8, 130.7, 130.13, 130.12, 130.0, 129.8, 128.8, 128.5, 126.93, 126.92, 126.81, 126.79, 126.76, 126.7, 126.5, 125.7, 124.3, 123.6, 123.5, 123.34, 123.26, 122.5, 121.5, 120.4, 42.7, 39.7, 31.9, 27.3, 27.2, 24.0, 23.44, 23.36.

[0441] HRMS (EI) calcd for [C 19 H 15 N] + requires m / z 257.1199, found m / z 257.1207.

[0442]

[0443] 2-(Quinolin-8-yl)cyclobutane-1-carbonitrile (26). The title compound was synthesized according to General Method A using 8-vinylquinoline (31.0 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (6:1 v / v) as the eluent to give 26.2 mg (0.126 mmol, 63% yield, 1.7:1 d.r.) of the title compound as a colorless oil.

[0444] 1 H NMR(CDCl 3 , 400 MHz): δ 8.95 (dd, J = 4.2, 1.8 Hz, 0.62H), 8.88 (dd, J = 4.2, 1.8 Hz, 0.38H), 8.19 - 8.12 (m, 1H), 7.79 - 7.71 (m, 1H), 7.70 - 7.65 (m, 0.38H), 7.61 - 7.48 (m, 1.62H), 7.45 - 7.39 (m, 1H), 4.98 - 4.76 (m, 1H), 3.98 - 3.85 (m, 0.38H), 3.54 - 3.40 (m, 0.62H), 2.97 - 2.86 (m, 0.38H), 2.68 - 2.21 (m, 3.62H).

[0445] 13 C NMR(CDCl 3 , 100 MHz): δ 149.4, 146.4, 146.2, 139.5, 137.7, 136.4, 136.1, 128.3, 128.2, 127.4, 127.3, 127.1, 126.21, 126.19, 126.0, 122.1, 121.6, 121.3, 121.2, 42.1, 38.3, 32.3, 28.5, 26.9, 24.2, 23.8, 23.4.

[0446] HRMS(EI) calcd for [C 14 H 12 N 2 + requires m / z 208.0995, found m / z 208.1004.

[0447]

[0448] ​2-(Isoquinolin-4-yl)cyclobutane-1-carbonitrile (27). The title compound was synthesized according to General Method A using 4-vinylisoquinoline (31.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (3:1 v / v) as the eluent to give 31.2 mg (0.150 mmol, 75% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0449] 1 H NMR(CDCl 3 , 400 MHz): δ 9.24 (s, 0.38H), 9.20 (s, 0.62H), 8.53 (s, 0.38H), 8.44 (s, 0.62H), 8.11 - 7.98 (m, 1.62H), 7.84 - 7.73 (m, 1.38H), 7.72 - 7.60 (m, 1H), 4.59 - 4.39 (m, 1H), 3.90 - 3.70 (m, 0.38H), 3.39 - 3.26 (m, 0.62H), 3.16 - 3.02 (m, 0.38H), 2.71 - 2.34 (m, 3.62H).

[0450] 13 C NMR(CDCl 3 , 100 MHz): δ 152.7, 152.4, 141.2, 139.7, 133.8, 133.7, 131.0, 130.9, 129.9, 128.8, 128.5, 128.2, 128.1, 127.5, 127.3, 122.7, 121.9, 121.1, 120.0, 40.5, 37.5, 31.5, 28.1, 26.2, 23.9, 23.72, 23.66.

[0451] HRMS (EI) calcd for [C 14 H 12 N 2 + requires m / z 208.0995, found m / z 208.1001.

[0452]

[0453] ​2-(Isoquinolin-5-yl)cyclobutane-1-carbonitrile (28). The title compound was synthesized according to General Method A using 5-vinylisoquinoline (31.1 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (3:1 v / v) as the eluent to give 20.1 mg (0.096 mmol, 48% yield, 1.7:1 d.r.) of the title compound as a colorless oil.

[0454] 1 H NMR(CDCl 3 , 400 MHz): δ 9.31 (brs, 1H), 8.62 (brs, 1H), 8.02 - 7.87 (m, 1H), 7.85 - 7.79 (m, 0.60H), 7.76 - 7.72 (m, 0.40H), 7.71 - 7.56 (m, 2H), 4.66 - 4.26 (m, 1H), 3.85 - 3.68 (m, 0.40H), 3.31 (q, J = 9.0 Hz, 0.60H), 3.14 - 2.93 (m, 0.40H), 2.67 - 2.33 (m, 3.60H).

[0455] 13 C NMR(CDCl 3 , 100 MHz): δ 153.3, 153.1, 143.5, 143.4, 136.2, 134.0, 133.82, 133.78, 129.6, 128.7, 128.1, 127.6, 127.3, 127.0, 126.83, 126.79, 125.9, 123.7, 121.1, 120.1, 41.8, 38.5, 31.6, 27.8, 26.9, 24.2, 23.4, 23.3.

[0456] HRMS (EI) calculated for [C 14 H 12 N 2 + requires m / z 208.0995, found m / z 208.1003.

[0457]

[0458] ​2-Methyl-2-(naphthalen-2-yl)cyclobutane-1-carbonitrile (29). The title compound was synthesized according to General Method A using 2-(prop-1-en-2-yl)naphthalene (68.0 mg, 0.4 mmol), acrylonitrile (132 μL, 2.0 mmol), 4-phenylmorpholine (39.2 mg, 0.24 mmol), UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol %), and 1,2-dichloroethane (0.2 mL). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (5:1 v / v) as the eluent to afford 49.6 mg (0.224 mmol, 56% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0459] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.86 - 7.78 (m, 3H), 7.56 - 7.43 (m, 3H), 7.32 - 7.26 (m, 1H), 3.43 (t, J = 9.2 Hz, 1H), 2.63 - 2.44 (m, 2H), 2.41 - 2.30 (m, 1H), 2.25 - 2.16 (m, 1H), 1.73 (s, 3H).

[0460] 13 C NMR(CDCl 3 , 100 MHz): δ 146.3, 133.2, 132.0, 128.6, 127.7, 127.6, 126.4, 125.8, 122.7, 122.3, 120.3, 45.8, 32.3, 32.0, 27.0, 21.3.

[0461] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.87 (d, J = 8.6 Hz, 1H), 7.85 - 7.80 (m, 2H), 7.65 (d, J = 2.0 Hz, 1H), 7.51 - 7.43 (m, 2H), 7.35 (dd, J = 8.6, 2.0 Hz, 1H), 3.28 - 3.19 (m, 1H), 3.07 - 2.96 (m, 1H), 2.68 - 2.56 (m, 1H), 2.32 - 2.16 (m, 2H), 1.65 (s, 3H).

[0462] 13 C NMR(CDCl 3, 100 MHz): δ 142.6, 133.3, 132.2, 128.4, 127.9, 127.7, 126.2, 125.8, 123.8, 123.7, 121.1, 46.6, 34.8, 31.2, 30.6, 21.1.

[0463] HRMS(EI) calculation for [C 16 H 15 N] + requires m / z 221.1199, found m / z 221.1193.

[0464]

[0465] 3-Methyl-2-(naphthalen-2-yl)cyclobutane-1-carbonitrile (30). The title compound was synthesized according to General Method A using 2-(prop-1-en-1-yl)naphthalene (E:Z = 4:1) (34.0 mg, 0.2 mmol) and acrylonitrile (66 μL, 1.0 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to afford 39.2 mg (0.178 mmol, 89% yield, 1.1:1 d.r.) of the title compound as a colorless oil.

[0466] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.86 - 7.78 (m, 3H), 7.64 (s, 1H), 7.52 - 7.44 (m, 2H), 7.36 (dd, J = 8.4, 1.8 Hz, 1H), 3.48 (t, J = 9.4 Hz, 1H), 3.08 - 2.96 (m, 1H), 2.69 - 2.50 (m, 2H), 2.02 (q, J = 10.0 Hz, 1H), 1.27 (d, J = 6.4 Hz, 3H).

[0467] 13 C NMR(CDCl 3 , 100 MHz): δ 137.7, 133.3, 132.6, 128.6, 127.69, 127.67, 126.4, 125.9, 124.8, 124.4, 121.4, 53.1, 36.1, 31.3, 25.9, 20.4.

[0468] Minor: 1 H NMR(CDCl 3, 400 MHz): δ 7.89 - 7.80 (m, 3H), 7.75 - 7.71 (m, 1H), 7.52 - 7.43 (m, 2H), 7.40 (dd, J = 8.4, 1.8 Hz, 1H), 3.62 - 3.39 (m, 2H), 3.31 - 3.14 (m, 1H), 2.50 - 2.41 (m, 1H), 2.14 - 2.03 (m, 1H), 1.25 (d, J = 6.4 Hz, 3H).

[0469] 13 C NMR(CDCl 3 , 100 MHz): δ 135.9, 133.3, 132.8, 128.4, 127.9, 127.7, 126.2, 126.0, 125.9, 125.4, 121.2, 49.6, 34.8, 30.8, 28.3, 20.3.

[0470] HRMS(EI) calcd for [C 16 H 15 N] + requires m / z 221.1199, found m / z 221.1187.

[0471]

[0472] 3,3 - Dimethyl - 2 - (naphthalen - 2 - yl)cyclobutane - 1 - carbonitrile (31). The title compound was synthesized according to General Method A using 2 - (2 - methylprop - 1 - en - 1 - yl)naphthalene (36.5 mg, 0.2 mmol), acrylonitrile (66 μL, 1.0 mmol) and UiO - 69 - phen(binap)Cu (5.9 mg, 1 μmol based on Cu, 0.5 mol%). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 45.1 mg (0.192 mmol, 96% yield, 1.2:1 d.r.) of the title compound as a colorless oil.

[0473] 1 H NMR(CDCl 3 , 400 MHz): δ 7.92 - 7.71 (m, 3.50H), 7.58 - 7.37 (m, 3H), 7.19 (d, J = 8.4 Hz, 0.50H), 3.81 - 3.38 (m, 2H), 2.42 - 2.03 (m, 2H), 1.41 - 1.29 (m, 3H), 1.10 (s, 1.50H), 0.76 (s, 1.50H).

[0474] 13 C NMR(CDCl 3, 100 MHz): δ 135.0, 134.9, 133.24, 133.19, 132.43, 132.38, 128.1, 127.9, 127.8, 127.7, 127.6, 127.5, 126.8, 126.3, 126.14, 126.09, 125.80, 125.79, 125.1, 124.9, 122.0, 121.8, 54.1, 51.3, 40.6, 39.7, 37.5, 36.9, 30.8, 30.4, 24.2, 22.9, 22.2, 20.5.

[0475] HRMS(EI) calculation for [C 17 H 17 N] + requires m / z 235.1356, found m / z 235.1356.

[0476]

[0477] 1-(Naphthalen-2-yl)spiro[3.3]heptane-2-carbonitrile (32). The title compound was synthesized according to General Method A using 2-(cyclobutylmethylene)naphthalene (38.9 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 46.9 mg (0.190 mmol, 95% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0478] 1 H NMR(CDCl 3 , 400 MHz): δ 7.90 - 7.80 (m, 3H), 7.81 - 7.73 (m, 0.44H), 7.59 - 7.54 (m, 0.56H), 7.53 - 7.43 (m, 2.44H), 7.29 (dd, J = 8.5, 1.9 Hz, 0.56H), 3.79 - 3.64 (m, 1H), 3.59 - 3.45 (m, 0.44H), 3.34 - 3.21 (m, 0.56H), 2.75 - 2.63 (m, 0.44H), 2.61 - 2.54 (m, 0.44H), 2.51 - 2.36 (m, 1H), 2.23 - 1.63 (m, 5.56H), 1.57 - 1.49 (m, 0.56H).

[0479] 13 C NMR(CDCl 3, 100 MHz): δ 135.0, 134.9, 133.31, 133.28, 132.58, 132.57, 128.3, 128.1, 127.9, 127.7, 127.63, 127.59, 127.4, 126.3, 126.2, 126.1, 125.9, 125.8, 125.7, 125.3, 121.4, 121.0, 53.7, 52.2, 47.2, 46.9, 38.3, 37.1, 35.4, 33.3, 30.7, 28.8, 24.3, 21.7, 15.89, 15.86.

[0480] HRMS (EI) calculation for [C 18 H 17 N] + requires m / z 247.1356, found m / z 247.1356.

[0481]

[0482] 1-(Naphthalen-2-yl)spiro[3.4]octane-2-carbonitrile (33). The title compound was synthesized according to General Method A using 2-(cyclopentylidenemethyl)naphthalene (41.6 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 26.8 mg (0.102 mmol, 51% yield, 1.0:1 d.r.) of the title compound as a colorless oil.

[0483] 1 H NMR (CDCl 3 , 400 MHz): δ 7.89 - 7.77 (m, 3.50H), 7.58 - 7.42 (m, 3H), 7.26 - 7.21 (m, 0.50H), 3.96 (d, J = 10.2 Hz, 0.50H), 3.76 (d, J = 9.2 Hz, 0.50H), 3.67 - 3.55 (m, 0.50H), 3.42 (q, J = 9.2 Hz, 0.50H), 2.54 - 2.20 (m, 2H), 1.95 - 1.76 (m, 2H), 1.65 - 1.26 (m, 6H).

[0484] 13 C NMR (CDCl 3, 100 MHz): δ 135.1, 135.0, 133.3, 133.2, 132.52, 132.50, 128.1, 127.90, 127.87, 127.7, 127.61, 127.56, 127.5, 126.5, 126.3, 126.1, 125.9, 125.8, 125.5, 125.4, 121.7, 121.4, 52.9, 51.4, 51.1, 51.0, 40.9, 39.9, 38.0, 37.6, 34.3, 32.6, 24.0, 23.7, 23.6, 23.5, 23.4, 21.4.

[0485] HRMS (EI) calculation for [C 19 H 19 N] + requires m / z 261.1512, found m / z 261.1515.

[0486]

[0487] 1-(Naphthalen-2-yl)spiro[3.5]nonane-2-carbonitrile (34). The title compound was synthesized according to General Method A using 2-(cyclohexylidene)naphthalene (44.5 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 28.2 mg (0.102 mmol, 51% yield, 1.0:1 d.r.) of the title compound as a colorless oil.

[0488] 1 H NMR (CDCl 3 , 400 MHz): δ 7.92 - 7.73 (m, 3.50H), 7.58 - 7.41 (m, 3H), 7.26 - 7.19 (m, 0.50H), 3.70 (d, J = 10.2 Hz, 0.50H), 3.67 - 3.55 (m, 1H), 3.47 (q, J = 9.2 Hz, 0.50H), 2.44 - 2.08 (m, 2H), 1.88 - 0.76 (m, 10H).

[0489] 13 C NMR (CDCl 3, 100 MHz): δ 134.4, 134.24, 133.20, 133.1, 132.47, 132.45, 128.0, 127.9, 127.7, 127.6, 127.5, 127.0, 126.3, 126.1, 125.82, 125.77, 125.3, 122.1, 121.7, 54.5, 51.9, 44.1, 40.5, 39.5, 35.3, 33.9, 33.2, 30.9, 25.6, 25.5, 22.93, 22.91, 22.8, 21.90, 21.86, 20.5.

[0490] HRMS (EI) calculation for [C 20 H 21 N] + requires m / z 275.1669, found m / z 275.1671.

[0491]

[0492] 2-(2-([1,1'-Biphenyl]-4-yl)-1-methylcyclobutyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (35). The title compound was synthesized according to General Method A using 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (168 mg, 1.0 mmol) and 4-vinyl-1,1'-biphenyl (36.1 mg, 0.2 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (30:1 v / v) as the eluent to give 31.3 mg (0.090 mmol, 45% yield, 3.4:1 d.r.) of the title compound as a colorless oil.

[0493] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.59 (d, J = 8.0 Hz, 2H), 7.53 (d, J = 8.0 Hz, 2H), 7.46 - 7.37 (m, 2H), 7.34 - 7.28 (m, 1H), 7.26 - 7.19 (m, 2H), 3.87 - 3.75 (m, 1H), 2.69 - 2.57 (m, 1H), 2.36 - 2.19 (m, 2H), 1.55 - 1.46 (m, 1H), 1.30 (s, 12H), 0.89 (s, 3H).

[0494] 13 C NMR (CDCl 3, 100 MHz): δ 141.6, 141.2, 138.3, 128.6, 127.9, 127.0, 126.9, 126.6, 83.2, 42.8, 27.1, 24.8, 24.7, 22.7, 17.5.

[0495] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.55 (d, J = 7.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.44 - 7.39 (m, 2H), 7.34 - 7.31 (m, 1H), 7.30 - 7.27 (m, 2H), 3.33 - 3.23 (m, 1H), 2.55 - 2.44 (m, 1H), 2.22 - 2.11 (m, 2H), 1.70 - 1.61 (m, 1H), 1.38 (s, 3H), 0.95 (s, 6H), 0.91 (s, 6H).

[0496] 13 C NMR(CDCl 3 , 100 MHz): δ 143.6, 141.5, 138.6, 128.7, 127.2, 127.0, 126.9, 126.6, 82.8, 50.4, 29.0, 26.2, 24.7, 24.6, 22.0.

[0497] HRMS(EI) calcd for [C 23 H 29 BO 2 + requires m / z 348.2255, found m / z 348.2250.

[0498]

[0499] 6-(2-Phenylcyclobutyl)quinoline (36). The title compound was synthesized according to General Method B using 6-vinylquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to afford 363 mg (1.40 mmol, 70% yield, 2.9:1 d.r.) of the title compound as a colorless oil.

[0500] 1 H NMR(CDCl 3 ​, 400 MHz): δ 9.37 - 8.96 (m, 1H), 8.59 - 8.37 (m, 1H), 7.90 (d, J = 8.4 Hz, 0.75H), 7.70 - 7.57 (m, 1.75H), 7.53 - 7.46 (m, 1H), 7.44 (s, 0.25H), 7.36 - 7.29 (m, 1.50H), 7.27 - 7.20 (m, 2.25H), 7.13 - 6.91 (m, 1.50H), 4.28 - 4.08 (m, 0.50H), 3.84 - 3.63 (m, 1.50H), 2.65 - 2.49 (m, 1H), 2.48 - 2.35 (m, 1.50H), 2.32 - 2.18 (m, 1.50H).

[0501] 13 C NMR(CDCl 3 , 100 MHz): δ 149.7, 149.5, 147.3, 146.9, 144.2, 142.9, 141.0, 140.2, 135.7, 135.6, 130.7, 129.3, 129.1, 128.4, 128.3, 128.2, 127.80, 127.78, 126.6, 126.2, 125.7, 125.4, 124.4, 121.1, 120.8, 47.9, 47.8, 45.3, 45.1, 26.0, 25.9, 24.3, 24.2。

[0502] HRMS(EI) calculated for [C 19 H 17 N] + requires m / z 259.1356, found m / z 259.1360。

[0503]

[0504] 6-(2-(4-Methoxyphenyl)cyclobutyl)quinoline (37). The title compound was synthesized using 6-vinylquinoline (312 mg, 2.0 mmol) and 1-methoxy-4-vinylbenzene (1.3 mL, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 440 mg (1.52 mmol, 76% yield, 3.2:1 d.r.) of the title compound as a colorless oil.

[0505] 1 H NMR(CDCl 3, 400 MHz): δ 8.86 (s, 1H), 8.15 - 7.75 (m, 2H), 7.66 - 7.28 (m, 2.52H), 7.25 - 7.11 (m, 2H), 6.92 - 6.81 (m, 2H), 6.57 (d, J = 8.8 Hz, 0.48H), 4.25 - 4.02 (m, 0.48H), 3.83 - 3.55 (m, 4.52H), 2.62 - 2.47 (m, 0.96H), 2.45 - 2.31 (m, 1.52H), 2.28 - 2.13 (m, 1.52H).

[0506] 13 C NMR(CDCl 3 , 100 MHz): δ 158.1, 157.5, 142.9, 140.3, 136.3, 135.71, 135.65, 133.2, 130.8, 129.30, 129.26, 129.2, 129.1, 128.8, 127.6, 125.4, 124.4, 113.82, 113.77, 113.7, 113.2, 55.2, 55.0, 48.2, 47.5, 45.1, 44.6, 26.3, 25.6, 24.6, 24.1.

[0507] HRMS(EI) calcd for [C 20 H 19 NO] + requires m / z 289.1461, found m / z 289.1462.

[0508]

[0509] 4-(2-(Quinolin-6-yl)cyclobutyl)phenyl acetate (38). The title compound was synthesized using 6-vinylquinoline (313 mg, 2.0 mmol) and 4-vinylphenyl acetate (1.6 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 425 mg (1.34 mmol, 67% yield, 3.3:1 d.r.) of the title compound as a colorless oil.

[0510] 1 H NMR(CDCl 3, 400 MHz): δ 8.86 (dd, J = 4.2, 1.6 Hz, 0.77H), 8.79 (dd, J = 4.2, 1.6 Hz, 0.23H), 8.10 (dd, J = 8.4, 1.0 Hz, 0.77H), 8.06 - 8.02 (m, 0.77H), 8.01 - 7.98 (m, 0.23H), 7.80 (d, J = 8.4 Hz, 0.23H), 7.65 - 7.57 (m, 1.54H), 7.41 - 7.34 (m, 1H), 7.33 - 7.29 (m, 0.23H), 7.28 - 7.21 (m, 1.77H), 7.05 - 6.99 (m, 1.54H), 6.95 (d, J = 8.4 Hz, 0.46H), 6.76 (d, J = 8.4 Hz, 0.46H), 4.30 - 3.99 (m, 0.46H), 3.81 - 3.59 (m, 1.54H), 2.63 - 2.46 (m, 0.92H), 2.46 - 2.34 (m, 1.54H), 2.32 - 2.16 (m, 4.54H).

[0511] 13 C NMR(CDCl 3 , 100 MHz): δ 169.7, 169.4, 149.8, 149.6, 149.0, 148.6, 147.3, 146.9, 142.6, 141.8, 139.9, 138.7, 135.8, 135.7, 130.6, 129.4, 129.0, 128.7, 128.5, 128.2, 127.9, 127.5, 125.5, 124.4, 121.4, 121.2, 120.9, 120.8, 47.9, 47.3, 45.0, 44.7, 26.0, 25.9, 24.4, 24.2, 21.1, 21.0.

[0512] HRMS(EI) calculated [C 21 H 19 NO 2 + requires m / z 317.1410, found m / z 317.1410.

[0513]

[0514] ​6-(2-(p-Tolyl)cyclobutyl)quinoline (39). The title compound was synthesized according to General Method B using 6-vinylquinoline (312 mg, 2.0 mmol) and 1-methyl-4-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 355 mg (1.30 mmol, 65% yield, 3.1:1 d.r.) of the title compound as a colorless oil.

[0515] 1 H NMR(CDCl 3 , 400 MHz): δ 9.20 (s, 0.75H), 9.09 (s, 0.25H), 8.56 - 8.33 (m, 1H), 7.89 (d, J = 8.4 Hz, 0.75H), 7.73 - 7.38 (m, 3H), 7.22 - 7.03 (m, 3.25H), 6.84 (s, 1H), 4.28 - 4.01 (m, 0.50H), 3.84 - 3.56 (m, 1.50H), 2.60 - 2.13 (m, 7H).

[0516] 13 C NMR(CDCl 3 , 100 MHz): δ 149.7, 149.5, 147.2, 146.9, 143.0, 141.2, 140.4, 138.0, 135.8, 135.78, 135.72, 135.1, 130.8, 129.3, 129.08, 129.07, 128.5, 128.3, 128.20, 128.19, 127.7, 126.5, 125.4, 124.3, 121.1, 120.8, 47.9, 47.7, 45.0, 44.9, 26.1, 25.7, 24.4, 24.2, 21.0, 20.8.

[0517] HRMS(EI) calcd for [C 20 H 19 N] + requires m / z 273.1512, found m / z 273.1514.

[0518]

[0519] 6-(2-(4-Chlorophenyl)cyclobutyl)quinoline (40). The title compound was synthesized using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-chloro-4-vinylbenzene (1.4 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 305 mg (1.04 mmol, 52% yield, 2.9:1 d.r.) of the title compound as a colorless oil.

[0520] 1 H NMR(CDCl 3 , 400 MHz): δ 9.21 (s, 0.75H), 9.10 (s, 0.25H), 8.57 - 8.39 (m, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.70 - 7.41 (m, 3H), 7.30 - 7.26 (m, 1H), 7.21 - 7.05 (m, 2H), 7.02 - 6.96 (m, 0.50H), 6.91 - 6.79 (m, 0.50H), 4.25 - 4.06 (m, 0.50H), 3.79 - 3.58 (m, 1.50H), 2.68 - 2.49 (m, 1H), 2.47 - 2.35 (m, 1.50H), 2.32 - 2.14 (m, 1.50H).

[0521] 13 C NMR(CDCl 3 , 100 MHz): δ 152.1, 152.0, 146.6, 143.1, 143.0, 142.9, 142.4, 136.0, 135.6, 132.0, 129.12, 129.07, 128.5, 128.4, 128.0, 127.9, 127.8, 127.6, 126.97, 126.95, 126.8, 126.5, 124.1, 123.11, 123.06, 120.3, 48.3, 47.3, 45.3, 44.6, 26.0, 25.5, 24.4, 23.8.

[0522] HRMS(EI) calcd for [C 19 H 16 ClN] + requires m / z 293.0966, found m / z 293.0969.

[0523]

[0524] 6-(2-(4-Fluorophenyl)cyclobutyl)quinoline (41). The title compound was synthesized according to General Method B using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-fluoro-4-vinylbenzene (1.2 g, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to afford 372 mg (1.34 mmol, 67% yield, 2.8:1 d.r.) of the title compound as a colorless oil.

[0525] 1 H NMR(CDCl 3 , 400 MHz): δ 8.86 (dd, J = 4.2, 1.8 Hz, 0.74H), 8.80 (dd, J = 4.2, 1.8 Hz, 0.26H), 8.13 - 8.03 (m, 1.48H), 8.02 - 7.97 (m, 0.26H), 7.80 (d, J = 8.8 Hz, 0.26H), 7.62 - 7.56 (m, 1.48H), 7.42 - 7.35 (m, 1H), 7.34 - 7.29 (m, 0.26H), 7.24 - 7.18 (m, 1.74H), 7.03 - 6.95 (m, 1.48H), 6.92 - 6.87 (m, 0.52H), 6.75 - 6.67 (m, 0.52H), 4.22 - 4.04 (m, 0.52H), 3.77 - 3.56 (m, 1.48H), 2.62 - 2.47 (m, 1.04H), 2.46 - 2.35 (m, 1.48H), 2.30 - 2.13 (m, 1.48H).

[0526] 19 F NMR(CDCl 3 , 376 MHz): δ -116.9, -117.4.

[0527] 13 C NMR(CDCl 3, 100 MHz): δ 161.4 (d, J = 244.1 Hz), 161.0 (d, J = 243.8 Hz), 149.8, 149.6, 147.3, 146.9, 142.5, 139.9, 139.8 (d, J = 3.2 Hz), 136.7 (d, J = 3.2 Hz), 135.8, 135.7, 130.6, 129.4, 129.1 (d, J = 7.8 Hz), 129.0, 128.5, 128.2, 128.0 (d, J = 7.8 Hz), 127.9, 125.5, 124.4, 121.2, 120.9, 115.1 (d, J = 21.2 Hz), 114.6 (d, J = 21.1 Hz), 48.2, 47.4, 45.0, 44.5, 26.1, 25.7, 24.4, 23.9.

[0528] HRMS (EI) calculation for [C 19 H 16 FN] + requires m / z 277.1261, found m / z 277.1262.

[0529]

[0530] 6-(2-(4-(Trifluoromethyl)phenyl)cyclobutyl)quinoline (42). The title compound was synthesized using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-(trifluoromethyl)-4-vinylbenzene (1.7 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to give 563 mg (1.72 mmol, 86% yield, 3.3:1 d.r.) of the title compound as a colorless oil.

[0531] 1 H NMR (CDCl 3, 400 MHz): δ 8.87 (dd, J = 4.2, 1.6 Hz, 0.77 H), 8.80 (dd, J = 4.2, 1.6 Hz, 0.23 H), 8.11 (dd, J = 8.4, 1.6 Hz, 0.77 H), 8.08 - 8.04 (m, 0.77 H), 7.99 (dd, J = 8.4, 1.6 Hz, 0.23 H), 7.80 (d, J = 8.7 Hz, 0.23 H), 7.64 - 7.59 (m, 1.54 H), 7.56 (d, J = 8.2 Hz, 1.54 H), 7.41 - 7.27 (m, 3.23 H), 7.23 (dd, J = 8.8, 2.0 Hz, 0.23 H), 7.06 (d, J = 8.4 Hz, 0.46 H), 4.29 - 4.10 (m, 0.46 H), 3.85 - 3.67 (m, 1.54 H), 2.65 - 2.49 (m, 0.92 H), 2.48 - 2.39 (m, 1.54 H), 2.35 - 2.20 (m, 1.54 H).

[0532] 19 F NMR(CDCl 3 , 376 MHz): δ -62.3, -62.4.

[0533] 13 C NMR(CDCl 3 , 100 MHz): δ 149.9, 149.7, 148.1, 147.2, 146.9, 145.3, 142.2, 139.5, 135.8, 135.7, 130.4, 129.5, 128.9, 128.67, 128.65, 128.5 (q, J = 31.8 Hz), 128.2 (q, J = 32.1 Hz), 128.0, 126.9, 125.6, 125.5, 125.3 (q, J = 3.8 Hz), 124.7 (q, J = 3.8 Hz), 124.5, 124.3 (q, J = 270.2 Hz), 124.2 (q, J = 270.2 Hz), 121.3, 121.0, 47.9, 47.6, 45.0, 25.9, 25.7, 24.24, 24.18.

[0534] HRMS(EI) calculated for [C 20 H 16 F 3 N] + requires m / z 327.1229, found m / z 327.1231.

[0535]

[0536] 6-(2-(m-Tolyl)cyclobutyl)quinoline (43). The title compound was synthesized using 6-vinylquinoline (313 mg, 2.0 mmol) and 1-methyl-3-vinylbenzene (1.2 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 421 mg (1.54 mmol, 77% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0537] 1 H NMR(CDCl 3 , 400 MHz): δ 8.85 (dd, J = 4.4, 1.8 Hz, 0.75H), 8.78 (dd, J = 4.4, 1.8 Hz, 0.25H), 8.12 - 8.07 (m, 0.75H), 8.06 - 7.98 (m, 1H), 7.79 (d, J = 8.8 Hz, 0.25H), 7.64 - 7.56 (m, 1.50H), 7.41 (d, J = 2.0 Hz, 0.25H), 7.36 (dd, J = 8.4, 4.4 Hz, 0.75H), 7.30 (dd, J = 8.4, 4.4 Hz, 0.25H), 7.24 - 7.17 (m, 1H), 7.09 - 7.01 (m, 2.25H), 6.93 - 6.88 (m, 0.25H), 6.79 - 6.71 (m, 0.75H), 4.24 - 4.02 (m, 0.50H), 3.85 - 3.57 (m, 1.50H), 2.61 - 2.47 (m, 1H), 2.44 - 2.35 (m, 1.50H), 2.33 (s, 2.25H), 2.27 - 2.18 (m, 1.50H), 2.10 (s, 0.75H).

[0538] 13 C NMR(CDCl 3 , 100 MHz): δ 149.6, 149.3, 147.2, 146.8, 144.1, 143.0, 140.9, 140.4, 138.0, 137.1, 135.80, 135.75, 130.8, 129.3, 129.1, 128.7, 128.3, 128.21, 128.19, 127.8, 127.6, 127.3, 127.0, 126.5, 125.4, 124.8, 124.4, 123.7, 121.1, 120.8, 47.9, 47.7, 45.2, 45.1, 26.1, 25.9, 24.3, 24.2, 21.5, 21.3.

[0539] HRMS(EI) calcd for [C 20 H19 N] + The required m / z is 273.1512, and the measured m / z is 273.1514.

[0540]

[0541] 6-(2-(3-Fluorophenyl)cyclobutyl)quinoline (44). The title compound was synthesized using 6-vinylquinoline (310 mg, 2.0 mmol) and 1-fluoro-3-vinylbenzene (1.2 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to give 316 mg (1.14 mmol, 57% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0542] 1 H NMR(CDCl 3 , 400 MHz): δ 8.86 (dd, J = 4.4, 1.6 Hz, 0.75H), 8.79 (dd, J = 4.4, 1.6 Hz, 0.25H), 8.10 (dd, J = 8.4, 1.6 Hz, 0.75H), 8.07 - 8.02 (m, 0.75H), 8.00 (dd, J = 8.4, 2.0 Hz, 0.25H), 7.80 (d, J = 8.8 Hz, 0.25H), 7.65 - 7.58 (m, 1.50H), 7.41 (d, J = 2.0 Hz, 0.25H), 7.37 (dd, J = 8.4, 4.4 Hz, 0.75H), 7.31 (dd, J = 8.4, 4.4 Hz, 0.25H), 7.28 - 7.26 (m, 0.25H), 7.26 - 7.21 (m, 0.75H), 7.03 - 6.87 (m, 2.50H), 6.74 - 6.59 (m, 0.75H), 4.27 - 4.03 (m, 0.50H), 3.80 - 3.60 (m, 1.50H), 2.66 - 2.49 (m, 1H), 2.46 - 2.35 (m, 1.50H), 2.31 - 2.14 (m, 1.50H).

[0543] 19 F NMR(CDCl 3 , 376 MHz): δ -113.3, -114.1.

[0544] 13 C NMR(CDCl 3, 100 MHz): δ 163.0 (d, J = 245.6 Hz), 162.6 (d, J = 244.8 Hz), 149.8, 149.6, 147.3, 146.9, 146.8 (d, J = 6.9 Hz), 143.9 (d, J = 6.9 Hz), 142.4, 139.7, 135.8, 135.7, 130.5, 129.8 (d, J = 8.3 Hz), 129.5, 129.1 (d, J = 8.3 Hz), 128.9, 128.6, 128.2, 127.9, 125.4, 124.4, 123.6 (d, J = 2.7 Hz), 122.3 (d, J = 2.8 Hz), 121.2, 120.9, 114.5 (d, J = 21.1 Hz), 113.4 (d, J = 20.9 Hz), 113.1 (d, J = 21.1 Hz), 112.6 (d, J = 21.0 Hz), 47.8, 47.6 (d, J = 1.7 Hz), 45.01, 44.96 (d, J = 1.6 Hz), 25.9, 25.8, 24.13, 24.08。

[0545] HRMS (EI) calculation for [C 19 H 16 FN] + requires m / z 277.1261, found m / z 277.1263。

[0546]

[0547] 6-(2-(o-Tolyl)cyclobutyl)quinoline (45). The title compound was synthesized using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-methyl-2-vinylbenzene (1.2 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to give 519 mg (1.90 mmol, 95% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0548] 1 H NMR (CDCl 3, 400 MHz): δ 8.84 (dd, J = 4.4, 1.6 Hz, 0.75H), 8.76 (dd, J = 4.4, 1.6 Hz, 0.25H), 8.16 - 7.98 (m, 1.50H), 7.93 (dd, J = 8.4, 1.8 Hz, 0.25H), 7.75 (d, J = 8.8 Hz, 0.25H), 7.68 - 7.56 (m, 1.50H), 7.45 - 7.33 (m, 1.75H), 7.30 - 7.26 (m, 0.50H), 7.24 - 7.17 (m, 1H), 7.14 - 7.11 (m, 1.50H), 7.05 - 6.98 (m, 0.25H), 6.96 - 6.85 (m, 0.50H), 4.33 - 4.14 (m, 0.50H), 4.05 - 3.67 (m, 1.50H), 2.75 - 2.56 (m, 1H), 2.50 - 2.41 (m, 1.50H), 2.29 - 2.18 (m, 3H), 2.12 - 2.01 (m, 1.50H).

[0549] 13 C NMR(CDCl 3 , 100 MHz): δ 149.7, 149.5, 147.2, 146.9, 143.0, 141.9, 140.4, 138.6, 136.2, 135.9, 135.74, 135.71, 130.6, 130.2, 130.1, 129.8, 129.3, 129.0, 128.3, 128.2, 126.3, 126.1, 126.0, 125.9, 125.62, 125.60, 125.4, 124.3, 121.1, 120.8, 45.5, 45.2, 42.4, 26.7, 26.1, 25.2, 23.1, 19.74, 19.71.

[0550] HRMS(EI) calculated [C 20 H 19 N] + requires m / z 273.1512, found m / z 273.1514.

[0551]

[0552] 6-(2-(2-Fluorophenyl)cyclobutyl)quinoline (46). The title compound was synthesized using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-fluoro-2-vinylbenzene (1.2 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to afford 360 mg (1.30 mmol, 65% yield, 2.5:1 d.r.) of the title compound as a colorless oil.

[0553] 1 H NMR(CDCl 3 , 400 MHz): δ 8.85 (dd, J = 4.4, 1.6 Hz, 0.71H), 8.77 (dd, J = 4.4, 1.6 Hz, 0.29H), 8.09 (d, J = 8.0 Hz, 0.71H), 8.04 (d, J = 9.2 Hz, 0.71H), 7.99 (d, J = 8.0 Hz, 0.29H), 7.78 (d, J = 8.8 Hz, 0.29H), 7.65 - 7.58 (m, 1.42H), 7.45 (d, J = 2.0 Hz, 0.29H), 7.41 - 7.28 (m, 2H), 7.21 - 7.17 (m, 0.71H), 7.15 - 7.09 (m, 0.71H), 7.07 - 7.05 (m, 0.29H), 7.01 - 6.94 (m, 0.71H), 6.94 - 6.88 (m, 0.29H), 6.88 - 6.78 (m, 0.29H), 6.76 - 6.66 (m, 0.29H), 4.44 - 4.17 (m, 0.58H), 4.08 - 3.77 (m, 1.42H), 2.71 - 2.34 (m, 2.58H), 2.32 - 2.10 (m, 1.42H).

[0554] 19 F NMR(CDCl 3 , 376 MHz): δ -116.2, -117.1.

[0555] 13 C NMR(CDCl 3, 100 MHz): δ 160.8 (d, J = 245.3 Hz), 160.6 (d, J = 244.2 Hz), 149.8, 149.5, 147.3, 146.9, 142.6, 140.0, 135.8, 135.7, 130.8, 130.6, 130.4, 129.3, 129.0, 128.4, 128.21, 128.19, 128.1 (d, J = 5.0 Hz), 128.0 (d, J = 5.0 Hz), 127.8 (d, J = 8.2 Hz), 127.5 (d, J = 8.4 Hz), 125.3, 124.3, 124.1 (d, J = 3.6 Hz), 123.4 (d, J = 3.4 Hz), 121.1, 120.8, 115.3 (d, J = 22.3 Hz), 114.5 (d, J = 22.2 Hz), 46.3, 44.9, 41.2 (d, J = 0.9 Hz), 38.5 (d, J = 1.7 Hz), 26.6, 25.9 (d, J = 1.9 Hz), 24.1, 22.7.

[0556] HRMS (EI) calculation for [C 19 H 16 FN] + requires m / z 277.1261, found m / z 277.1260.

[0557]

[0558] 6-(2-(Pyridin-2-yl)cyclobutyl)quinoline (47). The title compound was synthesized using 6-vinylquinoline (312 mg, 2.0 mmol) and 2-vinylpyridine (1.1 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to give 427 mg (1.64 mmol, 82% yield, 2.6:1 d.r.) of the title compound as a colorless oil.

[0559] 1 H NMR (CDCl 3, 400 MHz): δ 8.85 (dd, J = 4.4, 1.6 Hz, 0.72H), 8.77 (dd, J = 4.4, 1.6 Hz, 0.28H), 8.67 - 8.60 (m, 0.72H), 8.40 - 8.33 (m, 0.28H), 8.09 (d, J = 8.2 Hz, 0.72H), 8.02 (d, J = 8.8 Hz, 0.72H), 8.00 - 7.96 (m, 0.28H), 7.75 (d, J = 8.8 Hz, 0.28H), 7.66 - 7.55 (m, 2H), 7.43 (d, J = 2.0 Hz, 0.28H), 7.36 (dd, J = 8.4, 4.4 Hz, 0.72H), 7.33 - 7.20 (m, 1H), 7.18 - 7.10 (m, 1.44H), 6.90 - 6.78 (m, 0.56H), 4.36 - 4.18 (m, 0.56H), 4.14 - 4.01 (m, 0.72H), 3.84 - 3.73 (m, 0.72H), 2.79 - 2.24 (m, 4H).

[0560] 13 C NMR(CDCl 3 , 100 MHz): δ 162.5, 160.7, 149.7, 149.6, 149.5, 148.7, 147.2, 146.8, 142.9, 140.1, 136.3, 135.74, 135.69, 135.5, 130.4, 129.3, 129.1, 128.3, 128.2, 127.8, 125.5, 124.3, 122.8, 121.8, 121.5, 121.1, 120.81, 120.78, 49.7, 47.1, 46.0, 44.7, 25.5, 24.9, 24.3, 22.6.

[0561] HRMS(EI) calculated for [C 18 H 16 N 2 + requires m / z 260.1308, found m / z 260.1309.

[0562]

[0563] ​6-(2-(1-Methyl-1H-indol-5-yl)cyclobutyl)quinoline (48). The title compound was synthesized using 6-vinylquinoline (311 mg, 2.0 mmol) and 1-methyl-5-vinyl-1H-indole (1.6 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to afford 524 mg (1.68 mmol, 84% yield, 3.6:1 d.r.) of the title compound as a colorless oil.

[0564] 1 H NMR(CDCl 3 , 400 MHz): δ 8.83 (dd, J = 4.4, 1.6 Hz, 0.78H), 8.73 (dd, J = 4.4, 1.6 Hz, 0.22H), 8.07 (d, J = 8.4 Hz, 0.78H), 8.01 (d, J = 9.2 Hz, 0.78H), 7.96 (d, J = 8.4 Hz, 0.22H), 7.71 (d, J = 8.8 Hz, 0.22H), 7.65 - 7.59 (m, 1.56H), 7.53 (s, 0.78H), 7.46 (d, J = 2.0 Hz, 0.22H), 7.37 - 7.31 (m, 1H), 7.28 - 7.23 (m, 1.22H), 7.14 (dd, J = 8.4, 1.7 Hz, 0.78H), 7.02 (d, J = 3.1 Hz, 0.78H), 6.91 (d, J = 8.4 Hz, 0.22H), 6.88 (d, J = 3.2 Hz, 0.22H), 6.73 (dd, J = 8.4, 1.6 Hz, 0.22H), 6.43 (d, J = 3.2 Hz, 0.78H), 6.28 (d, J = 3.2 Hz, 0.22H), 4.31 - 4.17 (m, 0.44H), 3.86 - 3.70 (m, 3.90H), 3.61 (s, 0.66H), 2.64 - 2.52 (m, 0.88H), 2.49 - 2.36 (m, 1.56H), 2.34 - 2.18 (m, 1.56H).

[0565] 13 C NMR(CDCl 3, 100 MHz): δ 149.6, 149.2, 147.2, 146.8, 143.4, 140.9, 135.8, 135.7, 135.6, 135.2, 131.9, 131.0, 129.3, 129.2, 129.1, 128.52, 128.48, 128.21, 128.16, 128.1, 127.9, 125.3, 124.3, 122.2, 121.0, 120.8, 120.6, 119.4, 118.3, 109.1, 108.5, 100.6, 100.4, 48.5, 48.3, 45.4, 45.3, 32.8, 32.7, 26.8, 25.6, 25.0, 24.4.

[0566] HRMS(EI) calculation for [C 22 H 20 N 2 + Calcd for m / z 312.1621, found 312.1623.

[0567]

[0568] 6-(2-(Benzofuran-5-yl)cyclobutyl)quinoline (49). The title compound was synthesized using 6-vinylquinoline (312 mg, 2.0 mmol) and 5-vinylbenzofuran (1.4 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to afford 479 mg (1.60 mmol, 80% yield, 3.8:1 d.r.) of the title compound as a colorless oil.

[0569] 1 H NMR (CDCl 3 ​, 400 MHz): δ 8.86 (s, 0.79H), 8.75 (s, 0.21H), 8.09 (d, J = 8.4 Hz, 0.79H), 8.04 (d, J = 9.2 Hz, 0.79H), 7.96 (dd, J = 8.4, 1.6 Hz, 0.21H), 7.73 (d, J = 8.8 Hz, 0.21H), 7.67 - 7.56 (m, 2.21H), 7.51 - 7.40 (m, 2H), 7.36 (dd, J = 8.4, 4.4 Hz, 0.79H), 7.30 - 7.22 (m, 0.79H), 7.19 (dd, J = 8.4, 1.6 Hz, 0.79H), 7.12 (d, J = 8.4 Hz, 0.21H), 6.84 (dd, J = 8.4, 1.6 Hz, 0.21H), 6.72 (d, J = 2.2 Hz, 0.79H), 6.55 (d, J = 2.2 Hz, 0.21H), 4.27 - 4.13 (m, 0.42H), 3.89 - 3.66 (m, 1.58H), 2.63 - 2.53 (m, 0.84H), 2.48 - 2.38 (m, 1.58H), 2.32 - 2.21 (m, 1.58H).

[0570] 13 C NMR (CDCl 3 , 100 MHz): δ 153.8, 153.3, 149.7, 149.4, 147.3, 146.8, 145.2, 144.7, 142.9, 140.3, 138.8, 135.8, 135.65, 135.63, 130.7, 129.3, 129.1, 128.3, 128.2, 127.8, 127.5, 127.0, 125.4, 124.5, 124.4, 123.2, 121.1, 120.8, 119.8, 118.7, 111.1, 110.5, 106.5, 106.4, 48.4, 48.0, 45.23, 45.17, 26.5, 25.8, 24.8, 24.2.

[0571] HRMS (EI) calculated for [C 21 H 17 NO] + requires m / z 299.1305, found m / z 299.1307.

[0572]

[0573] 6-(2-(Benzo[b]thiophen-5-yl)cyclobutyl)quinoline (50). The title compound was synthesized according to General Method B using 6-vinylquinoline (310 mg, 2.0 mmol) and 5-vinylbenzofuran (1.6 g, 2.0 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (4:1 v / v) as the eluent to afford 536 mg (1.70 mmol, 85% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0574] 1 H NMR(CDCl 3 , 400 MHz): δ 8.85 (dd, J = 4.4, 1.6 Hz, 0.75H), 8.74 (dd, J = 4.4, 1.6 Hz, 0.25H), 8.10 - 8.01 (m, 1.50H), 7.94 (dd, J = 8.4, 1.6 Hz, 0.25H), 7.80 (d, J = 8.4 Hz, 0.75H), 7.73 (d, J = 8.8 Hz, 0.25H), 7.70 (s, 0.75H), 7.64 - 7.59 (m, 1.50H), 7.50 - 7.45 (m, 0.50H), 7.44 - 7.39 (m, 1H), 7.35 (dd, J = 8.4, 4.4 Hz, 0.75H), 7.29 - 7.23 (m, 2.25H), 7.12 (d, J = 5.4 Hz, 0.25H), 6.87 (dd, J = 8.4, 1.6 Hz, 0.25H), 4.28 - 4.17 (m, 0.50H), 3.87 - 3.71 (m, 1.50H), 2.66 - 2.52 (m, 1H), 2.50 - 2.37 (m, 1.50H), 2.33 - 2.20 (m, 1.50H).

[0575] 13 C NMR(CDCl 3 , 100 MHz): δ 149.7, 149.4, 147.2, 146.8, 142.8, 140.4, 140.2, 139.8, 139.4, 137.7, 137.4, 137.2, 135.8, 135.6, 130.7, 129.3, 129.1, 128.4, 128.2, 127.8, 126.7, 126.1, 125.4, 124.8, 124.4, 123.7, 123.6, 123.5, 122.4, 122.2, 121.7, 121.2, 121.1, 120.8, 48.1, 48.0, 45.15, 45.14, 26.3, 25.8, 24.6, 24.3.

[0576] HRMS(EI) calculation [C 21 H 17 NS] + The required m / z is 315.1076, and the measured m / z is 315.1080.

[0577]

[0578] Methyl 2-phenyl-3-(quinolin-6-yl)cyclobutane-1-carboxylate (51). The title compound was synthesized using 6-vinylquinoline (310 mg, 2.0 mmol) and methyl cinnamate (1.6 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (6:1 → 3:1 v / v) as the eluent to give 387 mg (1.22 mmol, 61% yield, 2.0:1 d.r.) of the title compound as a colorless oil.

[0579] 1 H NMR(CDCl 3 , 400 MHz): δ 9.40 - 8.97 (m, 1H), 8.62 - 8.38 (m, 1H), 7.94 (d, J = 8.4 Hz, 0.67H), 7.69 (s, 0.67H), 7.68 - 7.61 (m, 1H), 7.60 - 7.52 (m, 1.33H), 7.36 - 7.24 (m, 3.33H), 7.10 (dd, J = 8.4, 1.6 Hz, 0.33H), 7.06 - 6.97 (m, 1H), 6.94 - 6.87 (m, 0.67H), 4.40 (t, J = 9.2 Hz, 0.33H), 4.24 - 4.16 (m, 0.33H), 3.96 (t, J = 9.8 Hz, 0.67H), 3.81 - 3.66 (m, 4H), 3.36 - 3.26 (m, 0.67H), 2.98 - 2.85 (m, 0.33H), 2.80 - 2.68 (m, 1H), 2.55 - 2.50 (m, 0.67H).

[0580] 13 C NMR(CDCl 3, 100 MHz): δ 174.9, 174.4, 151.7, 151.4, 146.0, 143.9, 142.6, 142.0, 141.5, 138.5, 136.1, 135.8, 128.8, 128.6, 128.4, 128.1, 128.0, 127.5, 127.2, 127.1, 127.04, 127.00, 126.6, 126.4, 124.3, 123.7, 120.6, 52.03, 51.97, 50.7, 47.6, 43.7, 42.6, 41.5, 40.5, 29.2, 26.7.

[0581] HRMS(EI) calculation [C 21 H 19 NO 2 + Requires m / z 317.1410, measured m / z 317.1411.

[0582]

[0583] 1-(2-Phenyl-3-(quinolin-6-yl)cyclobutyl)ethan-1-one (52). The title compound was synthesized using 6-vinylquinoline (313 mg, 2.0 mmol) and (E)-4-phenylbut-3-en-2-one (1.5 g, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (6:1 → 3:1 v / v) as the eluent to give 361 mg (1.20 mmol, 60% yield, 2.0:1 d.r.) of the title compound as a colorless oil.

[0584] 1 H NMR(CDCl 3 ​, 400 MHz): δ 9.22 (s, 0.67H), 9.11 (s, 0.33H), 8.49 (d, J = 6.0 Hz, 0.67H), 8.45 (d, J = 6.0 Hz, 0.33H), 7.92 (d, J = 8.4 Hz, 0.67H), 7.69 - 7.57 (m, 2H), 7.54 (s, 0.33H), 7.50 - 7.45 (m, 0.67H), 7.39 - 7.28 (m, 3.33H), 7.08 - 6.89 (m, 2H), 4.28 - 4.20 (m, 0.33H), 4.15 - 4.08 (m, 0.33H), 3.83 - 3.71 (m, 1.67H), 3.46 - 3.37 (m, 0.67H), 2.89 - 2.82 (m, 0.33H), 2.73 - 2.66 (m, 1H), 2.50 - 2.42 (m, 0.67H), 2.15 (s, 0.99H), 2.11 (s, 2.01H).

[0585] 13 C NMR(CDCl 3 , 100 MHz): δ 208.3, 208.0, 151.4, 151.0, 146.4, 144.3, 142.0, 141.5, 141.4, 138.6, 136.2, 135.9, 129.1, 128.81, 128.77, 128.12, 128.09, 127.7, 127.2, 126.9, 126.6, 124.2, 123.5, 120.7, 50.6, 49.8, 48.4, 47.6, 43.0, 41.8, 28.5, 28.3, 27.8, 24.9.

[0586] HRMS(EI) calculated for [C 21 H 19 NO] + requires m / z 301.1461, found m / z 301.1458.

[0587]

[0588] 4-(2-Phenylcyclobutyl)-1,1'-biphenyl (53). The title compound was synthesized according to General Method B using 4-vinyl-1,1'-biphenyl (360 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane as the eluent to give 466 mg (1.64 mmol, 82% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0589] 1 H NMR(CDCl3 , 400 MHz): δ 7.61 - 7.47 (m, 3.50H), 7.45 - 7.17 (m, 9H), 7.10 - 6.94 (m, 1.50H), 4.11 - 3.98 (m, 0.50H), 3.68 - 3.55 (m, 1.50H), 2.54 - 2.42 (m, 1H), 2.41 - 2.27 (m, 1.50H), 2.24 - 2.09 (m, 1.50H).

[0590] 13 C NMR(CDCl 3 , 100 MHz): δ 144.5, 143.7, 141.4, 141.1, 141.0, 140.7, 139.0, 138.2, 128.7, 128.6, 128.33, 128.32, 127.9, 127.7, 127.05, 127.02, 126.99, 126.9, 126.8, 126.6, 126.3, 126.1, 126.0, 125.6, 47.9, 47.6, 45.3, 45.0, 26.0, 25.9, 24.4, 24.2.

[0591] HRMS(EI) calculated for [C 22 H 20 + requires m / z 284.1560, found m / z 284.1564.

[0592]

[0593] Methyl 4-(2-phenylcyclobutyl)benzoate (54). The title compound was synthesized according to General Method B using methyl 4-vinylbenzoate (324 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to give 442 mg (1.66 mmol, 83% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0594] 1 H NMR(CDCl 3 ​, 400 MHz): δ 7.96 (d, J = 8.4 Hz, 1.50H), 7.75 (d, J = 8.4 Hz, 0.50H), 7.33 - 7.26 (m, 3H), 7.24 - 7.17 (m, 2.25H), 7.10 - 7.04 (m, 0.50H), 7.03 - 6.97 (m, 0.75H), 6.94 - 6.89 (m, 0.50H), 4.11 - 3.98 (m, 0.50H), 3.89 (s, 2.25H), 3.83 (s, 0.75H), 3.67 - 3.53 (m, 1.50H), 2.53 - 2.43 (m, 1H), 2.39 - 2.29 (m, 1.50H), 2.23 - 2.11 (m, 1.50H).

[0595] 13 C NMR(CDCl 3 , 100 MHz): δ 167.2, 167.1, 149.8, 147.2, 144.0, 140.9, 129.7, 129.0, 128.4, 128.0, 127.83, 127.78, 127.7, 127.3, 126.6, 126.5, 126.3, 125.7, 52.0, 51.8, 47.9, 47.8, 45.3, 45.2, 25.9, 25.6, 24.1, 24.0.

[0596] HRMS(EI) calculated for [C 18 H 18 O 2 + requires m / z 266.1301, found m / z 266.1306.

[0597]

[0598] 1-(4-(2-Phenylcyclobutyl)phenyl)ethan-1-one (55). The title compound was synthesized using 1-(4-vinylphenyl)ethan-1-one (292 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to give 415 mg (1.66 mmol, 83% yield, 3.3:1 d.r.) of the title compound as a colorless oil.

[0599] 1 H NMR(CDCl 3 ​, 400 MHz): δ 7.89 (d, J = 8.4 Hz, 1.54 H), 7.68 (d, J = 8.4 Hz, 0.46 H), 7.34 - 7.27 (m, 3.08 H), 7.24 - 7.18 (m, 2.23 H), 7.12 - 7.06 (m, 0.46 H), 7.04 - 6.99 (m, 0.77 H), 6.96 - 6.89 (m, 0.46 H), 4.16 - 4.02 (m, 0.46 H), 3.70 - 3.52 (m, 1.54 H), 2.58 (s, 2.31 H), 2.54 - 2.43 (m, 1.61 H), 2.40 - 2.30 (m, 1.54 H), 2.24 - 2.12 (m, 1.54 H).

[0600] 13 C NMR(CDCl 3 , 100 MHz): δ 198.0, 197.8, 150.1, 147.6, 144.0, 140.9, 135.2, 134.6, 128.5, 128.4, 128.0, 127.84, 127.82, 127.7, 126.8, 126.5, 126.3, 125.8, 47.90, 47.86, 45.3, 45.2, 26.6, 26.5, 25.9, 25.6, 24.2, 24.1.

[0601] HRMS(EI) calculated for [C 18 H 18 O] + requires m / z 250.1352, found m / z 250.1352.

[0602]

[0603] 4-(2-Phenylcyclobutyl)benzaldehyde (56). The title compound was synthesized according to General Method B using 4-vinylbenzaldehyde (264 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to afford 402 mg (1.70 mmol, 85% yield, 3.6:1 d.r.) of the title compound as a colorless oil.

[0604] 1 H NMR(CDCl 3, 400 MHz): δ 9.97 (s, 0.78H), 9.85 (s, 0.22H), 7.81 (d, J = 8.2 Hz, 1.56H), 7.59 (d, J = 8.2 Hz, 0.44H), 7.40 - 7.19 (m, 5.44H), 7.12 - 6.90 (m, 1.56H), 4.16 - 3.98 (m, 0.44H), 3.75 - 3.51 (m, 1.56H), 2.58 - 2.45 (m, 0.88H), 2.43 - 2.28 (m, 1.56H), 2.27 - 2.11 (m, 1.56H).

[0605] 13 C NMR(CDCl 3 , 100 MHz): δ 192.1, 192.0, 151.7, 149.2, 143.8, 140.8, 134.6, 134.0, 129.9, 129.2, 128.5, 128.4, 127.8, 127.7, 127.2, 126.6, 126.4, 125.9, 47.94, 47.93, 45.41, 45.38, 26.0, 25.6, 24.1, 24.0.

[0606] HRMS(EI) calculated for [C 17 H 16 O] + requires m / z 236.1196, found m / z 236.1202.

[0607]

[0608] N,N - Diethyl - 4 - (2 - phenylcyclobutyl)benzamide (57). The title compound was synthesized according to General Method B using N,N - diethyl - 4 - vinylbenzamide (407 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to give 516 mg (1.68 mmol, 84% yield, 4.7:1 d.r.) of the title compound as a colorless oil.

[0609] 1 H NMR(CDCl 3, 400 MHz): δ 7.33 - 7.17 (m, 7.36H), 7.11 - 6.89 (m, 1.64H), 4.17 - 3.94 (m, 0.36H), 3.73 - 2.96 (m, 5.64H), 2.56 - 2.42 (m, 0.72H), 2.41 - 2.25 (m, 1.64H), 2.22 - 2.06 (m, 1.64H), 1.28 - 1.05 (m, 6H).

[0610] 13 C NMR(CDCl 3 , 100 MHz): δ 171.5, 171.4, 145.6, 144.2, 142.6, 141.1, 135.0, 134.3, 128.3, 127.9, 127.8, 127.6, 126.60, 126.58, 126.4, 126.2, 125.6, 125.5, 47.9, 47.7, 45.3, 45.1, 43.3, 39.2, 25.9, 25.8, 23.9, 23.7, 14.1, 13.0.

[0611] HRMS(EI) calculated for [C 21 H 25 NO] + requires m / z 307.1931, found m / z 307.1935.

[0612]

[0613] trans-1-(2-Phenylcyclobutyl)naphthalene (58). The title compound was synthesized according to General Method B using 1-vinylnaphthalene (308 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane as the eluent to afford 362 mg (1.40 mmol, 70% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0614] 1 H NMR(CDCl 3 , 400 MHz): δ 7.96 - 7.89 (m, 1H), 7.87 - 7.80 (m, 1H), 7.71 (d, J = 8.0 Hz, 1H), 7.53 - 7.39 (m, 4H), 7.35 - 7.26 (m, 4H), 7.23 - 7.15 (m, 1H), 4.27 (q, J = 9.2 Hz, 1H), 3.99 (q, J = 9.2 Hz, 1H), 2.71 - 2.59 (m, 1H), 2.50 - 2.39 (m, 1H), 2.33 - 2.21 (m, 1H), 2.16 - 2.04 (m, 1H).

[0615] 13 C NMR (CDCl 3 , 100 MHz): δ 144.6, 140.4, 133.7, 131.6, 128.6, 128.3, 126.7, 126.6, 126.1, 125.57, 125.55, 125.5, 124.2, 122.8, 44.8, 44.7, 28.0, 26.6。

[0616] HRMS (EI) calculated for [C 20 H 18 + requires m / z 258.1403, found m / z 258.1409。

[0617]

[0618] trans-1-Fluoro-4-(2-phenylcyclobutyl)naphthalene (59). The title compound was synthesized according to General Method B using 1-fluoro-4-vinylnaphthalene (343 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane as the eluent to afford 359 mg (1.30 mmol, 65% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0619] 1 H NMR (CDCl 3 , 400 MHz): δ 8.13 - 8.10 (m, 1H), 7.89 (d, J = 8.4 Hz, 1H), 7.56 - 7.44 (m, 2H), 7.42 - 7.35 (m, 1H), 7.32 - 7.27 (m, 4H), 7.22 - 7.17 (m, 1H), 7.13 - 7.05 (m, 1H), 4.28 - 4.12 (m, 1H), 3.99 - 3.85 (m, 1H), 2.69 - 2.55 (m, 1H), 2.50 - 2.38 (m, 1H), 2.33 - 2.19 (m, 1H), 2.14 - 1.99 (m, 1H)。

[0620] 19 F NMR (CDCl 3 , 376 MHz): δ -126.0。

[0621] 13 C NMR (CDCl 3 ​, 100 MHz): δ 157.5 (d, J = 250.1 Hz), 144.4, 136.2 (d, J = 4.2 Hz), 132.7 (d, J = 4.3 Hz), 128.4, 126.6, 126.5, 126.2, 125.8 (d, J = 1.9 Hz), 124.2 (d, J = 2.8 Hz), 123.9 (d, J = 16.1 Hz), 122.4 (d, J = 8.2 Hz), 121.0 (d, J = 5.8 Hz), 108.7 (d, J = 19.6 Hz), 45.0, 44.4, 27.9, 26.5.

[0622] HRMS (EI) calculation for [C 20 H 17 F] + requires m / z 276.1309, found m / z 276.1315.

[0623]

[0624] 2-(2-Phenylcyclobutyl)naphthalene (60). The title compound was synthesized according to General Method B using 2-vinylnaphthalene (308 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane as the eluent to afford 418 mg (1.62 mmol, 81% yield, 6.7:1 d.r.) of the title compound as a colorless oil.

[0625] 1 H NMR (CDCl 3 , 400 MHz): δ 7.82 - 7.63 (m, 3.87H), 7.51 - 7.17 (m, 7.13H), 7.11 - 6.91 (m, 1H), 4.21 - 4.07 (m, 0.26H), 3.82 - 3.60 (m, 1.74H), 2.62 - 2.48 (m, 0.52H), 2.46 - 2.32 (m, 1.74H), 2.30 - 2.13 (m, 1.74H).

[0626] 13 C NMR (CDCl 3, 100 MHz): δ 144.5, 142.0, 141.5, 139.3, 133.5, 133.2, 132.2, 131.8, 128.3, 127.9, 127.7, 127.60, 127.58, 127.5, 127.4, 127.1, 127.0, 126.6, 126.1, 125.9, 125.7, 125.6, 125.5, 125.2, 124.9, 124.7, 48.2, 47.8, 45.3, 45.2, 26.0, 25.9, 24.4, 24.3.

[0627] HRMS (EI) calculation for [C 20 H 18 + requires m / z 258.1403, found m / z 258.1411.

[0628]

[0629] trans-9-(2-Phenylcyclobutyl)phenanthrene (61). The title compound was synthesized using 9-vinylphenanthrene (409 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane as the eluent to give 493 mg (1.60 mmol, 80% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0630] 1 H NMR (CDCl 3 , 400 MHz): δ 8.71 (d, J = 7.6 Hz, 1H), 8.63 (d, J = 7.6 Hz, 1H), 7.97 (dd, J = 8.0, 1.2 Hz, 1H), 7.84 (dd, J = 7.6, 1.6 Hz, 1H), 7.72 (s, 1H), 7.66 - 7.50 (m, 4H), 7.37 - 7.28 (m, 4H), 7.22 - 7.18 (m, 1H), 4.33 - 4.20 (m, 1H), 4.18 - 4.04 (m, 1H), 2.77 - 2.63 (m, 1H), 2.54 - 2.44 (m, 1H), 2.35 - 2.24 (m, 1H), 2.19 - 2.05 (m, 1H).

[0631] 13 C NMR (CDCl 3 ​, 100 MHz): δ 144.8, 138.6, 131.8, 130.9, 130.6, 129.5, 128.8, 128.4, 126.7, 126.6, 126.4, 126.2, 126.12, 126.10, 124.8, 123.4, 123.1, 122.4, 45.0, 44.0, 28.2, 26.55.

[0632] HRMS (EI) calculation for [C 24 H 20 + Requires m / z 308.1560, found m / z 308.1557.

[0633]

[0634] 4-(2-Phenylcyclobutyl)quinoline (62). The title compound was synthesized using 4-vinylquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (6:1 v / v) as the eluent to afford 410 mg (1.58 mmol, 79% yield, 4.5:1 d.r.) of the title compound as a colorless oil.

[0635] 1 H NMR (CDCl 3 , 400 MHz): δ 8.86 (d, J = 4.4 Hz, 0.82H), 8.66 (d, J = 4.4 Hz, 0.18H), 8.11 (d, J = 8.4 Hz, 0.82H), 7.99 - 7.90 (m, 0.36H), 7.84 (dd, J = 8.4, 1.6 Hz, 0.82H), 7.71 - 7.63 (m, 0.82H), 7.62 - 7.56 (m, 0.18H), 7.50 - 7.42 (m, 1H), 7.40 (dd, J = 4.4, 1.2 Hz, 0.82H), 7.35 - 7.19 (m, 4.18H), 7.10 (d, J = 4.4 Hz, 0.18H), 6.93 - 6.82 (m, 0.82H), 4.78 - 4.68 (m, 0.18H), 4.31 - 4.17 (m, 1H), 3.92 (q, J = 9.4 Hz, 0.82H), 2.94 - 2.76 (m, 0.18H), 2.74 - 2.59 (m, 1H), 2.56 - 2.26 (m, 2H), 2.22 - 2.10 (m, 0.82H).

[0636] 13 C NMR (CDCl 3 ​, 100 MHz): δ 150.4, 150.0, 149.8, 148.2, 147.7, 147.1, 143.7, 140.3, 130.0, 129.8, 129.0, 128.6, 128.5, 127.6, 127.4, 127.3, 127.0, 126.6, 126.5, 126.1, 126.0, 125.8, 124.00, 123.96, 118.9, 117.8, 46.5, 44.9, 44.1, 41.2, 27.3, 26.5, 24.4, 22.7.

[0637] HRMS(EI) calculation for [C 19 H 17 N] + requires m / z 259.1356, found m / z 259.1360.

[0638]

[0639] trans-4-(2-Phenylcyclobutyl)isoquinoline (63). The title compound was synthesized according to General Method B using 4-vinylisoquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to afford 322 mg (1.24 mmol, 62% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0640] 1 H NMR (CDCl 3 , 400 MHz): δ 9.13 (s, 1H), 8.57 (s, 1H), 8.02 - 7.92 (m, 1H), 7.84 - 7.76 (m, 1H), 7.66 - 7.53 (m, 2H), 7.36 - 7.27 (m, 4H), 7.24 - 7.18 (m, 1H), 4.18 (q, J = 9.2 Hz, 1H), 3.99 (q, J = 9.2 Hz, 1H), 2.67 - 2.57 (m, 1H), 2.52 - 2.41 (m, 1H), 2.40 - 2.27 (m, 1H), 2.26 - 2.13 (m, 1H).

[0641] 13 C NMR (CDCl 3 , 100 MHz): δ 151.3, 144.0, 140.2, 134.2, 133.1, 130.0, 128.4, 128.2, 126.8, 126.7, 126.4, 123.3, 45.3, 43.2, 27.1, 26.7.

[0642] HRMS(EI) calculation for [C 19 H 17 N] + Requires m / z 259.1356, measured m / z 259.1354.

[0643]

[0644] 6-(2-Phenylcyclobutyl)isoquinoline (64). The title compound was synthesized using 6-vinylisoquinoline (311 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol) according to General Method B. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to give 337 mg (1.30 mmol, 65% yield, 3.3:1 d.r.) of the title compound as a colorless oil.

[0645] 1 H NMR(CDCl 3 , 400 MHz): δ 8.85 (dd, J = 4.4, 1.6 Hz, 0.75H), 8.77 (dd, J = 4.4, 1.6 Hz, 0.25H), 8.08 (d, J = 8.0 Hz, 0.75H), 8.04 (d, J = 9.2 Hz, 0.75H), 7.98 (d, J = 8.4 Hz, 0.25H), 7.77 (d, J = 8.8 Hz, 0.25H), 7.63 - 7.59 (m, 1.25H), 7.40 - 7.19 (m, 5.75H), 7.07 - 7.00 (m, 0.50H), 6.98 - 6.93 (m, 0.50H), 4.25 - 4.06 (m, 0.50H), 3.85 - 3.60 (m, 1.50H), 2.63 - 2.48 (m, 1H), 2.46 - 2.34 (m, 1.50H), 2.30 - 2.16 (m, 1.50H).

[0646] 13 C NMR(CDCl 3 , 100 MHz): δ 149.7, 149.5, 147.2, 146.8, 144.2, 142.9, 141.0, 140.2, 135.8, 135.7, 132.8, 130.7, 129.3, 129.1, 128.4, 128.3, 128.2, 127.80, 127.78, 126.6, 126.2, 125.7, 125.4, 124.4, 121.1, 120.8, 47.9, 47.8, 45.3, 45.1, 26.0, 25.9, 24.25, 24.16.

[0647] HRMS(EI) calculation for [C 19 H 17 N] + Requires m / z 259.1356, measured m / z 259.1364.

[0648]

[0649] 5-(2-Phenylcyclobutyl)benzo[b]thiophene (65). The title compound was synthesized according to General Method B using 5-vinylbenzo[b]thiophene (320 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane as the eluent to give 423 mg (1.60 mmol, 80% yield, 3.2:1 d.r.) of the title compound as a colorless oil.

[0650] 1 H NMR (CDCl 3 , 400 MHz): δ 7.78 (d, J = 8.4 Hz, 0.76H), 7.68 (s, 0.76H), 7.54 (d, J = 8.4 Hz, 0.24H), 7.45 (s, 0.24H), 7.42 - 7.37 (m, 0.76H), 7.32 - 7.16 (m, 5.76H), 7.07 - 7.02 (m, 0.48H), 7.00 - 6.94 (m, 0.76H), 6.86 (dd, J = 8.4, 1.7 Hz, 0.24H), 4.20 - 3.94 (m, 0.48H), 3.78 - 3.52 (m, 1.52H), 2.58 - 2.44 (m, 0.96H), 2.43 - 2.29 (m, 1.52H), 2.26 - 2.10 (m, 1.52H).

[0651] 13 C NMR (CDCl 3 , 100 MHz): δ 144.5, 141.5, 140.8, 139.8, 139.4, 137.8, 137.6, 137.0, 128.3, 127.9, 127.7, 126.6, 126.5, 126.1, 125.9, 125.5, 125.1, 123.7, 123.6, 122.3, 122.2, 121.5, 121.2, 48.1, 47.9, 45.3, 45.1, 26.3, 25.8, 24.7, 24.3.

[0652] HRMS(EI) calculation for [C 18 H 16 S] +The required m / z is 264.0967, and the measured m / z is 264.0971.

[0653]

[0654] 2-Isopropyl-5-methylcyclohexyl 4-(2-phenylcyclobutyl)benzoate (66). The title compound was synthesized according to General Method B using (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl 4-vinylbenzoate (570 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (v / v 20:1) as the eluent to give 500 mg (1.28 mmol, 64% yield, 3.2:1 d.r.) of the title compound as a colorless oil.

[0655] 1 H NMR(CDCl 3 , 400 MHz): δ 7.97 (d, J = 8.4 Hz, 1.52H), 7.76 (d, J = 8.4 Hz, 0.48H), 7.33 - 7.25 (m, 3.04H), 7.24 - 7.17 (m, 2.24H), 7.12 - 7.06 (m, 0.48H), 7.05 - 6.92 (m, 1.24H), 4.98 - 4.80 (m, 1H), 4.14 - 3.97 (m, 0.48H), 3.70 - 3.46 (m, 1.52H), 2.55 - 2.41 (m, 0.96H), 2.39 - 2.28 (m, 1.52H), 2.22 - 2.05 (m, 2.52H), 2.01 - 1.88 (m, 1H), 1.78 - 1.65 (m, 2H), 1.60 - 1.45 (m, 2H), 1.19 - 1.01 (m, 2H), 0.95 - 0.86 (m, 7H), 0.82 - 0.73 (m, 3H).

[0656] 13 C NMR(CDCl 3, 100 MHz): δ 166.2, 166.1, 149.6, 147.0, 144.0, 141.1, 129.7, 129.0, 128.7, 128.4, 128.0, 127.83, 127.80, 127.77, 126.54, 126.52, 126.3, 125.7, 74.6, 74.5, 47.90, 47.87, 47.3, 47.2, 45.21, 45.15, 41.0, 40.9, 34.3, 31.41, 31.38, 26.5, 26.4, 25.9, 25.7, 24.34, 24.26, 23.6, 22.0, 20.7, 16.5。

[0657] HRMS(EI) calculation for [C 27 H 34 O 2 + Requires m / z 390.2553, found m / z 390.2563。

[0658]

[0659] 3-(4-Methoxyphenyl)-7-(2-phenylcyclobutyl)-4H-chromen-4-one (67). The title compound was synthesized according to General Method B using 3-(4-methoxyphenyl)-7-vinyl-4H-chromen-4-one (555 mg, 2.0 mmol) and styrene (1.1 mL, 10 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to afford 650 mg (1.70 mmol, 85% yield, 3.0:1 d.r.) of the title compound as a colorless oil.

[0660] 1 H NMR(CDCl 3 , 400 MHz): δ 8.21 (d, J = 8.2 Hz, 0.75H), 7.98 (d, J = 8.2 Hz, 0.25H), 7.95 (s, 0.75H), 7.87 (s, 0.25H), 7.53 - 7.44 (m, 2H), 7.38 - 7.21 (m, 5H), 7.13 - 6.89 (m, 4H), 4.19 - 4.06 (m, 0.50H), 3.87 - 3.81 (m, 3H), 3.75 - 3.56 (m, 1.50H), 2.60 - 2.45 (m, 1H), 2.44 - 2.31 (m, 1.50H), 2.29 - 2.14 (m, 1.50H).

[0661] 13 C NMR(CDCl 3 ​, 100 MHz): δ 176.4, 176.3, 159.55, 159.47, 156.4, 156.0, 152.3, 152.2, 151.2, 148.8, 143.6, 140.6, 130.1, 130.0, 128.5, 128.0, 127.7, 126.6, 126.4, 126.3, 126.0, 125.6, 125.4, 124.9, 124.7, 124.3, 124.2, 124.1, 122.7, 122.1, 116.4, 115.4, 113.94, 113.90, 55.31, 55.28, 47.9, 47.8, 45.3, 45.2, 25.9, 25.6, 24.074, 24.068.

[0662] HRMS(EI) calculation for [C 26 H 22 O 3 + Requires m / z 382.1563, found m / z 382.1552.

[0663]

[0664] tert-Butyl 6-cyano-5-(naphthalen-2-yl)-2-azaspiro[3.3]heptane-2-carboxylate (68). The title compound was synthesized according to General Method C using tert-butyl 3-(naphthalen-2-ylmethylene)azetidine-1-carboxylate (59.2 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to give 67.4 mg (0.194 mmol, 97% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0665] 1 H NMR(CDCl 3 , 400 MHz): δ 7.93 - 7.80 (m, 3H), 7.74 (s, 0.44H), 7.57 (s, 0.56H), 7.55 - 7.47 (m, 2H), 7.39 (dd, J = 8.4, 2.0 Hz, 0.44H), 7.26 (dd, J = 8.4, 2.0 Hz, 0.56H), 4.18 - 3.84 (m, 4H), 3.66 (s, 1H), 3.62 - 3.51 (m, 0.44H), 3.37 - 3.22 (m, 0.56H), 2.83 - 2.56 (m, 2H), 1.48 - 1.24 (m, 9H).

[0666] 13 C NMR(CDCl​3 , 100 MHz): δ 156.0, 155.9, 133.6, 133.31, 133.30, 133.28, 132.73, 132.70, 129.0, 128.8, 127.9, 127.72, 127.68, 127.6, 127.0, 126.6, 126.4, 126.3, 126.2, 125.5, 125.0, 124.3, 120.5, 119.9, 79.74, 79.73, 51.7, 50.3, 40.9, 40.8, 36.4, 34.9, 28.22, 28.19, 24.6, 21.8。

[0667] HRMS(EI) calculation for [C 22 H 24 N 2 O 2 + requires m / z 348.1832, found m / z 348.1830。

[0668]

[0669] 5-(Naphthalen-2-yl)-2-thiaspiro[3.3]heptane-6-carbonitrile (69). Prepared according to General Procedure C using 3-(naphthalen-2-ylmethylene)thiacyclobutane (42.6 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol) and UiO-69-phen(binap)Cu (8.9 mg, 1.5 μmol based on Cu, 0.75 mol%). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (6:1 v / v) as the eluent to afford 24.4 mg (0.092 mmol, 46% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0670] 1 H NMR (CDCl 3 , 400 MHz): δ 7.94 - 7.82 (m, 3.41H), 7.61 (s, 0.59H), 7.56 - 7.48 (m, 2.41H), 7.39 (dd, J = 8.4, 2.0 Hz, 0.59H), 3.80 - 3.73 (m, 1H), 3.63 - 3.52 (m, 1.41H), 3.34 - 3.16 (m, 2H), 3.08 (d, J = 9.2 Hz, 0.59H), 3.03 (d, J = 9.8 Hz, 0.41H), 2.90 - 2.73 (m, 2H), 2.60 - 2.52 (m, 0.59H)。

[0671] 13 ​13C NMR (CDCl 3 , 100 MHz): δ 133.5, 133.34, 133.28, 133.1, 132.8, 132.7, 128.8, 128.6, 128.0, 127.8, 127.73, 127.67, 127.2, 126.6, 126.4, 126.3, 126.2, 125.6, 125.5, 124.9, 120.7, 120.3, 54.9, 53.1, 50.6, 50.3, 39.8, 38.7, 38.2, 36.9, 34.3, 32.7, 23.6, 21.0.

[0672] HRMS (EI) calcd for [C 17 H 15 NS] + requires m / z 265.0920, found m / z 265.0918.

[0673]

[0674] 5-(Naphthalen-2-yl)-2-oxaspiro[3.3]heptane-6-carbonitrile (70). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.3 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to afford 47.4 mg (0.190 mmol, 95% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0675] Major: 1 1H NMR (CDCl 3 , 400 MHz): δ 7.91 (d, J = 8.4 Hz, 1H), 7.88 - 7.81 (m, 2H), 7.64 - 7.60 (m, 1H), 7.56 - 7.47 (m, 2H), 7.36 (dd, J = 8.4, 2.0 Hz, 1H), 4.83 (d, J = 7.2 Hz, 1H), 4.75 (d, J = 7.2 Hz, 1H), 4.46 (d, J = 6.8 Hz, 1H), 4.42 (d, J = 6.8 Hz, 1H), 4.02 (d, J = 9.8 Hz, 1H), 3.25 (q, J = 9.4 Hz, 1H), 2.79 - 2.60 (m, 2H).

[0676] 13 13C NMR (CDCl 3, 100 MHz): δ 133.8, 133.3, 132.8, 129.0, 127.8, 127.7, 126.7, 126.3, 125.6, 124.4, 120.7, 81.0, 78.0, 51.6, 46.2, 34.2, 22.0.

[0677] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.92 (d, J = 8.4 Hz, 1H), 7.89 - 7.82 (m, 2H), 7.77 (s, 1H), 7.55 - 7.46 (m, 2H), 7.42 (dd, J = 8.4, 2.0 Hz, 1H), 4.87 (d, J = 6.8 Hz, 1H), 4.80 (d, J = 6.8 Hz, 1H), 4.67 (q, J = 7.2 Hz, 2H), 4.00 (d, J = 8.8 Hz, 1H), 3.59 - 3.49 (m, 1H), 2.92 - 2.75 (m, 2H).

[0678] 13 C NMR(CDCl 3 , 100 MHz): δ 133.4, 133.3, 132.8, 128.9, 127.9, 127.7, 127.0, 126.5, 126.3, 125.0, 120.0, 82.5, 78.9, 50.0, 46.2, 35.8, 24.6.

[0679] HRMS(EI) calculated for [C 17 H 15 NO] + requires m / z 249.1148, found m / z 249.1152.

[0680]

[0681] 1-(Naphthalen-1-yl)spiro[3.3]heptane-2-carbonitrile (71). The title compound was synthesized using 3-(naphthalen-1-ylmethylene)oxetane (39.4 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to give 47.4 mg (0.190 mmol, 95% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0682] 1 H NMR(CDCl 3, 400 MHz): δ 8.11 (d, J = 8.2 Hz, 1H), 7.92 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 8.2 Hz, 1H), 7.64 - 7.45 (m, 3H), 7.19 (d, J = 7.2 Hz, 1H), 4.98 (d, J = 7.2 Hz, 1H), 4.76 - 4.65 (m, 2H), 4.37 (d, J = 6.6 Hz, 1H), 4.19 (d, J = 6.6 Hz, 1H), 3.42 (q, J = 8.8 Hz, 1H), 2.88 - 2.68 (m, 2H).

[0683] 13 C NMR(CDCl 3 , 100 MHz): δ 133.8, 133.3, 132.8, 129.0, 127.8, 127.7, 126.7, 126.3, 125.6, 124.4, 120.7, 81.0, 78.0, 51.6, 46.2, 34.2, 22.0.

[0684] HRMS(EI) calculated for [C 17 H 15 NO] + requires m / z 249.1148, found m / z 249.1139.

[0685]

[0686] 1 - ([1,1'-Biphenyl]-4-yl)spiro[3.3]heptane-2-carbonitrile (72). The title compound was synthesized using 3-([1,1'-biphenyl]-4-ylmethylene)oxetane (44.6 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (2:1 v / v) as the eluent to afford 46.3 mg (0.168 mmol, 84% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0687] Major: 1 H NMR(CDCl 3, 400 MHz): δ 7.65 (d, J = 8.2 Hz, 2H), 7.62 - 7.56 (m, 2H), 7.50 - 7.42 (m, 2H), 7.40 - 7.33 (m, 1H), 7.29 (d, J = 8.2 Hz, 2H), 4.78 (d, J = 7.2 Hz, 1H), 4.73 (d, J = 7.2 Hz, 1H), 4.53 - 4.44 (m, 2H), 3.90 (d, J = 9.8 Hz, 1H), 3.15 (q, J = 9.4 Hz, 1H), 2.78 - 2.57 (m, 2H).

[0688] 13 C NMR(CDCl 3 , 100 MHz): δ 140.9, 140.3, 135.2, 128.9, 127.8, 127.6, 127.2, 127.0, 120.6, 80.9, 78.0, 51.3, 46.2, 34.2, 22.1.

[0689] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.65 (d, J = 8.0 Hz, 2H), 7.61 (d, J = 7.4 Hz, 2H), 7.49 - 7.42 (m, 2H), 7.42 - 7.32 (m, 3H), 4.83 (d, J = 6.8 Hz, 1H), 4.77 (d, J = 6.8 Hz, 1H), 4.73 (d, J = 7.2 Hz, 1H), 4.65 (d, J = 7.2 Hz, 1H), 3.87 (d, J = 8.8 Hz, 1H), 3.49 (q, J = 8.0 Hz, 1H), 2.80 (d, J = 7.6 Hz, 2H).

[0690] 13 C NMR(CDCl 3 , 100 MHz): δ 140.7, 140.4, 134.7, 128.8, 128.1, 127.7, 127.5, 127.1, 120.0, 82.4, 78.8, 49.5, 46.2, 35.7, 24.7.

[0691] HRMS(EI) calculated for [C 19 H 17 NO] + requires m / z 275.1305, found m / z 275.1311.

[0692]

[0693] 1-(4-Chlorophenyl)spiro[3.3]heptane-2-carbonitrile (73). The title compound was synthesized according to General Method C using 3-(4-chlorobenzylidene)oxetane (36.2 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol), and UiO-69-phen(binap)Cu (11.9 mg, 2.0 μmol based on Cu, 1.0 mol%). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (3:1 v / v) as the eluent to give 18.7 mg (0.080 mmol, 40% yield, 1.1:1 d.r.) of the title compound as a colorless oil.

[0694] 1 H NMR(CDCl 3 , 400 MHz): δ 7.46 - 7.36 (m, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 4.77 (d, J = 3.2 Hz, 1H), 4.72 (s, 1H), 4.63 (d, J = 3.2 Hz, 1H), 4.47 (d, J = 6.6 Hz, 0.50H), 4.40 (d, J = 6.6 Hz, 0.50H), 3.83 (t, J = 9.2 Hz, 1H), 3.57 - 3.41 (m, 0.50H), 3.11 - 3.02 (m, 0.50H), 2.87 - 2.55 (m, 2H).

[0695] 13 C NMR(CDCl 3 , 100 MHz): δ 134.7, 134.3, 133.89, 133.88, 129.3, 129.2, 129.0, 128.1, 120.3, 119.7, 82.2, 80.8, 78.6, 77.7, 50.9, 49.2, 46.1, 35.5, 34.0, 24.6, 22.1.

[0696] HRMS(EI) calcd for [C 13 H 12 ClNO] + requires m / z 233.0602, found m / z 233.0605.

[0697]

[0698] 1-(4-Formylphenyl)spiro[3.3]heptane-2-carbonitrile (74). The title compound was synthesized according to General Method C using 4-(oxetan-3-ylidene)benzaldehyde (34.8 mg, 0.2 mmol), acrylonitrile (40 μL, 0.6 mmol) and UiO-69-phen(binap)Cu (5.9 mg, 1.0 μmol based on Cu, 0.5 mol%). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 → 1:1 v / v) as the eluent to give 27.3 mg (0.120 mmol, 60% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0699] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 10.05 (s, 1H), 7.96 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz, 2H), 4.82 - 4.71 (m, 2H), 4.50 (d, J = 6.8 Hz, 1H), 4.37 (d, J = 6.8 Hz, 1H), 3.97 (d, J = 10.0 Hz, 1H), 3.18 (q, J = 9.4 Hz, 1H), 2.78 - 2.60 (m, 2H).

[0700] 13 C NMR(CDCl 3 , 100 MHz): δ 191.4, 143.0, 135.9, 130.4, 127.4, 120.1, 80.8, 77.7, 51.3, 46.2, 34.0, 21.9.

[0701] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 10.04 (s, 1H), 7.97 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 4.88 - 4.75 (m, 2H), 4.70 - 4.58 (m, 2H), 3.94 (d, J = 8.8 Hz, 1H), 3.59 - 3.48 (m, 1H), 2.86 - 2.73 (m, 2H).

[0702] 13 C NMR(CDCl 3 , 100 MHz): δ 191.6, 142.6, 135.8, 130.3, 128.3, 119.5, 82.1, 78.6, 49.6, 46.1, 35.5, 24.5.

[0703] HRMS(EI) calculated for [C14 H 13 NO 2 + Requires m / z 227.0941, measured m / z 227.0939.

[0704]

[0705] 1-(4-Acetylphenyl)spiro[3.3]heptane-2-carbonitrile (75). The title compound was synthesized according to General Method C using 1-(4-(oxetan-3-ylmethylene)phenyl)ethan-1-one (37.7 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (2:1 v / v) as the eluent to give 44.9 mg (0.186 mmol, 93% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0706] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 8.03 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 4.83 - 4.69 (m, 2H), 4.48 (d, J = 6.8 Hz, 1H), 4.37 (d, J = 6.8 Hz, 1H), 3.94 (d, J = 9.8 Hz, 1H), 3.16 (q, J = 9.4 Hz, 1H), 2.78 - 2.59 (m, 5H).

[0707] 13 C NMR (CDCl 3 , 100 MHz): δ 197.3, 141.5, 136.6, 129.1, 126.9, 120.2, 80.8, 77.7, 51.2, 46.2, 34.1, 26.6, 21.9.

[0708] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 8.03 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 4.81 (q, J = 6.8 Hz, 2H), 4.64 (d, J = 2.0 Hz, 2H), 3.91 (d, J = 8.8 Hz, 1H), 3.57 - 3.44 (m, 1H), 2.86 - 2.74 (m, 2H), 2.63 (s, 3H).

[0709] 13 C NMR (CDCl 3 ​, 100 MHz): δ 197.4, 141.1, 136.6, 129.0, 127.9, 119.6, 82.2, 78.6, 49.6, 46.1, 35.5, 26.6, 24.5.

[0710] HRMS(EI) calculation [C 15 H 15 NO 2 + Requires m / z 241.1097, measured m / z 241.1103.

[0711]

[0712] Methyl 4-(2-cyanospiro[3.3]heptan-1-yl)benzoate (76). The title compound was synthesized using methyl 4-(oxetan-3-ylmethylene)benzoate (40.7 mg, 0.2 mmol) and acrylonitrile (40 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (2:1 v / v) as the eluent to afford 39.7 mg (0.154 mmol, 77% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0713] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 8.10 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 4.80 - 4.70 (m, 2H), 4.47 (d, J = 6.8 Hz, 1H), 4.36 (d, J = 6.8 Hz, 1H), 3.96 - 3.90 (m, 4H), 3.15 (q, J = 9.4 Hz, 1H), 2.77 - 2.57 (m, 2H).

[0714] 13 C NMR(CDCl 3 , 100 MHz): δ 166.5, 141.3, 130.4, 129.8, 126.7, 120.3, 80.8, 77.7, 52.2, 51.2, 46.2, 34.1, 21.9.

[0715] Minor: 1 H NMR(CDCl 3 ​, 400 MHz): δ 8.11 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 4.85 - 4.76 (m, 2H), 4.63 (s, 2H), 3.93 (s, 3H), 3.90 (d, J = 8.8 Hz, 1H), 3.56 - 3.44 (m, 1H), 2.84 - 2.73 (m, 2H).

[0716] 13 C NMR(CDCl 3 , 100 MHz): δ 166.6, 140.9, 130.3, 129.8, 127.7, 119.6, 82.3, 78.6, 52.2, 49.7, 46.1, 35.6, 24.5.

[0717] HRMS(EI) calcd for [C 15 H 15 NO 3 + requires m / z 257.1046, found m / z 257.1045.

[0718]

[0719] Ethyl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (77). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.3 mg, 0.2 mmol) and ethyl acrylate (64 μL, 0.6 mmol) according to General Procedure C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (7:1 v / v) as the eluent to afford 55.7 mg (0.188 mmol, 94% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0720] 1 H NMR(CDCl 3 ​, 400 MHz): δ 7.90 - 7.76 (m, 3H), 7.68 (s, 0.40H), 7.62 (s, 0.60H), 7.52 - 7.40 (m, 2.40H), 7.28 (dd, J = 8.4, 1.6 Hz, 0.60H), 4.90 - 4.79 (m, 1.60H), 4.74 (d, J = 6.8 Hz, 0.40H), 4.66 (s, 1.20H), 4.46 (d, J = 6.6 Hz, 0.40H), 4.41 (d, J = 6.4 Hz, 0.40H), 4.20 - 4.11 (m, 0.80H), 4.04 (d, J = 9.8 Hz, 0.60H), 3.92 (d, J = 9.2 Hz, 0.40H), 3.82 - 3.73 (m, 1.20H), 3.56 - 3.45 (m, 0.60H), 3.30 (q, J = 9.0 Hz, 0.40H), 2.90 (dd, J = 12.6, 7.0 Hz, 0.60H), 2.61 - 2.48 (m, 1.40H), 1.24 (t, J = 7.2 Hz, 1.20H), 0.79 (t, J = 7.2 Hz, 1.80H).

[0721] 13 C NMR(CDCl 3 , 100 MHz): δ 173.8, 173.0, 136.1, 135.4, 133.44, 133.35, 132.5, 132.3, 128.5, 128.1, 127.71, 127.66, 127.6, 127.5, 126.4, 126.2, 126.1, 125.8, 125.7, 125.6, 125.5, 125.3, 83.6, 81.8, 79.6, 78.8, 60.8, 60.3, 51.1, 50.1, 44.86, 44.84, 39.4, 37.6, 33.4, 33.0, 14.2, 13.7.

[0722] HRMS(EI) calculated for [C 19 H 20 O 3 + requires m / z 296.1407, found m / z 296.1408.

[0723]

[0724] ​Benzyl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (78). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and benzyl acrylate (97.3 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (7:1 v / v) as the eluent to afford 63.8 mg (0.178 mmol, 89% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0725] 1 H NMR(CDCl 3 , 400 MHz): δ 7.90 - 7.70 (m, 3H), 7.67 (s, 0.40H), 7.59 (s, 0.60H), 7.52 - 7.38 (m, 2.40H), 7.34 - 7.26 (m, 2H), 7.22 (dd, J = 8.4, 1.8 Hz, 0.60H), 7.15 - 7.07 (m, 0.60H), 7.03 - 6.94 (m, 1.20H), 6.80 - 6.72 (m, 1.20H), 5.13 (s, 0.80H), 4.87 - 4.77 (m, 1.60H), 4.76 - 4.66 (m, 1.60H), 4.60 (s, 1.20H), 4.45 (d, J = 6.6 Hz, 0.40H), 4.41 (d, J = 6.6 Hz, 0.40H), 4.03 (d, J = 9.8 Hz, 0.60H), 3.93 (d, J = 9.2 Hz, 0.40H), 3.62 - 3.50 (m, 0.60H), 3.36 (q, J = 9.1 Hz, 0.40H), 2.94 (dd, J = 12.7, 7.3 Hz, 0.60H), 2.63 - 2.47 (m, 1.40H).

[0726] 13 C NMR(CDCl 3 , 100 MHz): δ 173.6, 172.8, 135.9, 135.7, 135.3, 135.1, 133.4, 132.5, 132.4, 128.5, 128.23, 128.19, 128.17, 128.1, 128.0, 127.9, 127.8, 127.7, 127.62, 127.56, 126.7, 126.2, 126.1, 125.8, 125.72, 125.68, 125.22, 125.20, 83.6, 81.7, 79.6, 78.7, 66.5, 66.4, 51.3, 50.2, 44.9, 44.7, 39.4, 37.6, 33.5, 32.9.

[0727] HRMS(EI) calculation for [C 24 H 22 O 3 + m / z 358.1563 was required and m / z 358.1568 was measured.

[0728]

[0729] Prop-2-yn-1-yl 1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (79). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.0 mg, 0.2 mmol) and prop-2-yn-1-yl acrylate (66.1 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (8:1 v / v) as the eluent to give 42.9 mg (0.140 mmol, 70% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0730] 1 H NMR(CDCl 3 , 400 MHz): δ 7.91 - 7.76 (m, 3H), 7.70 - 7.65 (m, 0.40H), 7.63 - 7.59 (m, 0.60H), 7.53 - 7.38 (m, 2.40H), 7.28 (dd, J = 8.4, 2.0 Hz, 0.60H), 4.89 (d, J = 6.4 Hz, 0.60H), 4.87 - 4.80 (m, 1H), 4.78 - 4.64 (m, 2.40H), 4.47 (d, J = 6.4 Hz, 0.40H), 4.41 (d, J = 6.4 Hz, 0.40H), 4.40 - 4.31 (m, 0.60H), 4.31 - 4.22 (m, 0.60H), 4.14 - 4.02 (m, 0.60H), 3.95 (d, J = 9.3 Hz, 0.40H), 3.64 - 3.52 (m, 0.60H), 3.37 (q, J = 9.1 Hz, 0.40H), 2.99 - 2.89 (m, 0.60H), 2.63 - 2.53 (m, 1.40H), 2.47 (t, J = 2.4 Hz, 0.40H), 2.03 (t, J = 2.4 Hz, 0.60H).

[0731] 13 C NMR(CDCl 3 ​, 100 MHz): δ 173.0, 172.2, 135.7, 135.0, 133.4, 132.5, 132.4, 128.6, 128.3, 127.9, 127.8, 127.7, 127.5, 126.5, 126.3, 126.1, 125.9, 125.8, 125.7, 125.4, 125.2, 83.5, 81.8, 79.6, 78.7, 77.4, 77.0, 75.1, 74.5, 52.3, 51.7, 51.2, 50.1, 44.9, 44.8, 39.3, 37.3, 33.4, 33.0.

[0732] HRMS(EI) calculation for [C 20 H 18 O 3 + requires m / z 306.1250, found m / z 306.1245.

[0733]

[0734] Ethyl 2-methyl-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (80). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and ethyl methacrylate (75 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 54.6 mg (0.176 mmol, 88% yield, 1.2:1 d.r.) of the title compound as a colorless oil.

[0735] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.88 - 7.80 (m, 3H), 7.75 (s, 1H), 7.52 - 7.44 (m, 2H), 7.36 (dd, J = 8.4, 1.8 Hz, 1H), 5.00 (d, J = 6.8 Hz, 1H), 4.93 (d, J = 6.8 Hz, 1H), 4.87 (d, J = 6.8 Hz, 1H), 4.70 (d, J = 6.8 Hz, 1H), 4.23 (q, J = 7.2 Hz, 2H), 4.07 (s, 1H), 2.86 - 2.77 (m, 1H), 2.29 (d, J = 11.8 Hz, 1H), 1.32 (t, J = 7.2 Hz, 3H), 1.07 (s, 3H).

[0736] 13 C NMR(CDCl 3 ​, 100 MHz): δ 176.8, 134.9, 133.4, 132.2, 128.1, 127.8, 127.6, 127.0, 126.2, 126.1, 125.8, 83.5, 79.5, 61.0, 53.0, 44.0, 43.0, 42.2, 19.1, 14.2.

[0737] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.82 - 7.75 (m, 3H), 7.60 - 7.56 (m, 1H), 7.49 - 7.40 (m, 2H), 7.26 - 7.22 (m, 1H), 4.92 (d, J = 6.4 Hz, 1H), 4.85 (d, J = 6.4 Hz, 1H), 4.71 - 4.63 (m, 2H), 3.78 - 3.66 (m, 2H), 3.62 (d, J = 1.6 Hz, 1H), 3.13 - 2.99 (m, 1H), 2.25 (dd, J = 12.5, 1.8 Hz, 1H), 1.56 (s, 3H), 0.71 (t, J = 7.2 Hz, 3H).

[0738] 13 C NMR(CDCl 3 , 100 MHz): δ 175.1, 135.9, 133.4, 132.2, 128.1, 127.7, 127.5, 126.1, 126.0, 125.6, 125.2, 84.0, 79.9, 60.4, 58.8, 45.7, 42.4, 41.1, 25.8, 13.6.

[0739] HRMS(EI) calcd for [C 20 H 22 O 3 + requires m / z 310.1563, found m / z 310.1565.

[0740]

[0741] Methyl 2 - acetamido - 1 - (naphthalen - 2 - yl)spiro[3.3]heptane - 2 - carboxylate (81). The title compound was synthesized using 3 - (naphthalen - 2 - ylmethylene)oxetane (39.2 mg, 0.2 mmol) and methyl 2 - acetamidoacrylate (85.9 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to give 54.3 mg (0.160 mmol, 80% yield, 1.0:1 d.r.) of the title compound as a colorless oil.​

[0742] 1 1H NMR(CDCl 3 , 400 MHz): δ 7.91 - 7.77 (m, 3H), 7.65 (d, J = 16.2 Hz, 1H), 7.56 - 7.44 (m, 2H), 7.36 (dd, J = 8.6, 1.8 Hz, 0.50H), 7.25 (dd, J = 8.6, 1.9 Hz, 0.50H), 6.80 (brs, 0.50H), 5.56 (brs, 0.50H), 4.97 - 4.87 (m, 2.50H), 4.77 - 4.71 (m, 1H), 4.67 - 4.59 (m, 1H), 4.15 (d, J = 2.6 Hz, 0.50H), 3.81 (s, 1.50H), 3.48 (s, 1.50H), 3.30 (dd, J = 13.2, 2.6 Hz, 0.50H), 3.16 (d, J = 12.2 Hz, 0.50H), 2.92 (d, J = 12.2 Hz, 0.50H), 2.72 (d, J = 13.2 Hz, 0.50H), 2.05 (s, 1.50H), 1.68 (s, 1.50H).

[0743] 13 13C NMR(CDCl 3 , 100 MHz): δ 173.3, 173.1, 170.3, 170.0, 134.6, 133.4, 132.6, 132.2, 131.7, 128.8, 128.5, 128.4, 127.9, 127.7, 127.65, 127.60, 126.7, 126.5, 126.3, 125.85, 125.75, 124.6, 124.2, 83.9, 82.2, 79.3, 78.7, 60.5, 57.5, 55.5, 52.9, 52.6, 52.4, 42.6, 42.4, 42.1, 39.5, 24.0, 22.6.

[0744] HRMS (EI) calculated for [C 20 1 21 H 4 NO + requires m / z 339.1465, found m / z 339.1467.

[0745]

[0746] Methyl 2-fluoro-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxylate (82). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and methyl 2-fluoroacrylate (56 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (10:1 v / v) as the eluent to afford 45.0 mg (0.150 mmol, 75% yield, 1.6:1 d.r.) of the title compound as a colorless oil.

[0747] 1 H NMR(CDCl 3 , 400 MHz): δ 7.88 - 7.78 (m, 3.62H), 7.73 (s, 0.38H), 7.52 - 7.43 (m, 2.62H), 7.35 (d, J = 8.4 Hz, 0.38H), 4.99 (d, J = 7.4 Hz, 0.62H), 4.94 - 4.84 (m, 2H), 4.75 (d, J = 7.4 Hz, 0.62H), 4.71 - 4.61 (m, 0.76H), 4.27 - 4.16 (m, 1H), 3.85 (s, 1.14H), 3.59 (s, 1.86H), 3.13 - 3.02 (m, 0.38H), 3.00 - 2.93 (m, 0.62H), 2.92 - 2.81 (m, 0.38H), 2.72 - 2.61 (m, 0.62H).

[0748] 19 F NMR(CDCl 3 , 376 MHz): δ -142.1, -171.7.

[0749] 13 C NMR(CDCl 3, 100 MHz): δ 170.8 (d, J = 27.1 Hz), 170.3 (d, J = 27.5 Hz), 133.5, 133.3, 133.0, 132.6, 132.4, 131.1 (d, J = 1.7 Hz), 128.7, 128.3, 128.1 (d, J = 2.1 Hz), 127.9, 127.8, 127.64, 127.59, 126.34, 126.26, 126.13, 126.06 (d, J = 2.2 Hz), 126.0, 124.8, 124.0, 92.7 (d, J = 232.0 Hz), 92.5 (d, J = 224.7 Hz), 82.1 (d, J = 1.6 Hz), 80.9, 78.6 (d, J = 2.8 Hz), 78.4, 56.1 (d, J = 21.8 Hz), 55.6 (d, J = 21.1 Hz), 52.9, 52.5, 42.71 (d, J = 22.5 Hz), 42.70 (d, J = 2.5 Hz), 41.7 (d, J = 20.8 Hz), 39.4 (d, J = 16.0 Hz).

[0750] HRMS (EI) calculation for [C 18 H 17 FO 3 + Requires m / z 300.1156, found m / z 300.1157.

[0751]

[0752] N,N-Dimethyl-1-(naphthalen-2-yl)spiro[3.3]heptane-2-carboxamide (83). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and N,N-dimethylacrylamide (59.5 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (1:1 v / v) as the eluent to afford 44.9 mg (0.152 mmol, 76% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0753] 1 H NMR (CDCl 3 ​, 400 MHz): δ 7.88 - 7.75 (m, 3H), 7.62 (s, 1H), 7.51 - 7.42 (m, 2H), 7.38 (dd, J = 8.4, 2.0 Hz, 0.40H), 7.23 (dd, J = 8.4, 2.0 Hz, 0.60H), 4.86 - 4.77 (m, 1.60H), 4.72 (d, J = 6.8 Hz, 0.40H), 4.53 (d, J = 7.0 Hz, 0.60H), 4.48 (q, J = 6.6 Hz, 0.80H), 4.33 (d, J = 7.0 Hz, 0.60H), 4.05 - 3.95 (m, 1H), 3.69 - 3.56 (m, 0.60H), 3.44 (q, J = 8.6 Hz, 0.40H), 3.33 - 3.21 (m, 0.60H), 2.98 - 2.86 (m, 2.40H), 2.64 - 2.48 (m, 5H).

[0754] 13 C NMR(CDCl 3 , 100 MHz): δ 172.9, 171.4, 136.7, 134.9, 133.5, 133.3, 132.49, 132.45, 131.2, 128.5, 128.1, 127.7, 127.64, 127.60, 127.5, 127.3, 126.2, 126.1, 126.0, 125.8, 125.7, 125.5, 84.1, 82.5, 79.6, 79.1, 53.0, 49.6, 44.4, 44.3, 38.1, 36.93, 36.86, 36.4, 35.6, 35.1, 33.7, 33.2.

[0755] HRMS(EI) calculated for [C 19 H 21 NO 2 + requires m / z 295.1567, found m / z 295.1566.

[0756]

[0757] ​1-(1-(Naphthalen-2-yl)spiro[3.3]heptan-2-yl)propan-1-one (84). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and pent-1-en-3-one (50.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (5:1 v / v) as the eluent to give 53.8 mg (0.192 mmol, 96% yield, 1.3:1 d.r.) of the title compound as a colorless oil.

[0758] 1 H NMR(CDCl 3 , 400 MHz): δ 7.96 - 7.73 (m, 3H), 7.64 (s, 0.46H), 7.55 (s, 0.54H), 7.53 - 7.42 (m, 2H), 7.38 (dd, J = 8.4, 1.8 Hz, 0.46H), 7.08 (dd, J = 8.4, 1.8 Hz, 0.54H), 4.87 (d, J = 6.2 Hz, 0.54H), 4.82 (d, J = 6.2 Hz, 0.54H), 4.75 (d, J = 6.8 Hz, 0.46H), 4.68 (d, J = 6.8 Hz, 0.46H), 4.52 (d, J = 7.0 Hz, 0.54H), 4.47 (d, J = 6.5 Hz, 0.46H), 4.43 - 4.34 (m, 1H), 4.10 (d, J = 10.1 Hz, 0.54H), 3.76 (d, J = 9.1 Hz, 0.46H), 3.70 - 3.57 (m, 0.54H), 3.46 (q, J = 8.9 Hz, 0.46H), 3.20 - 3.08 (m, 0.54H), 2.58 - 2.38 (m, 2.46H), 2.06 - 1.78 (m, 1H), 1.02 (t, J = 7.3 Hz, 1.62H), 0.62 (t, J = 7.3 Hz, 1.38H).

[0759] 13 C NMR(CDCl 3 , 100 MHz): δ 210.5, 210.3, 136.1, 135.1, 133.5, 133.4, 132.6, 132.4, 128.7, 128.5, 127.7, 127.6, 127.3, 126.4, 126.3, 126.0, 125.92, 125.90, 125.52, 125.47, 84.4, 81.9, 79.4, 78.9, 53.2, 50.1, 45.8, 44.3, 43.9, 35.0, 34.5, 32.3, 32.2, 7.5, 7.2.

[0760] HRMS (EI) calculation for [C 19 H 20 O 2 + m / z 280.1458 was required and m / z 280.1459 was measured.

[0761]

[0762] 4,4,5,5 - Tetramethyl - 2-(1-(naphthalen - 2 - yl)spiro[3.3]hept - 2 - yl)-1,3,2 - dioxaborolane (85). The title compound was synthesized according to General Method C using 3-(naphthalen - 2 - ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 4,4,5,5 - tetramethyl - 2 - vinyl - 1,3,2 - dioxaborolane (92.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to afford 63.7 mg (0.182 mmol, 91% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0763] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.84 - 7.75 (m, 3H), 7.70 (s, 1H), 7.49 - 7.39 (m, 3H), 4.90 (d, J = 6.4 Hz, 1H), 4.83 (d, J = 6.4 Hz, 1H), 4.63 (d, J = 7.2 Hz, 1H), 4.59 (d, J = 7.2 Hz, 1H), 3.89 (d, J = 9.9 Hz, 1H), 2.57 - 2.48 (m, 1H), 2.47 - 2.37 (m, 1H), 2.35 - 2.24 (m, 1H), 0.94 (s, 6H), 0.93 (s, 6H).

[0764] 13 C NMR (CDCl 3 , 100 MHz): δ 139.2, 133.4, 132.1, 127.9, 127.55, 127.54, 125.89, 125.85, 125.6, 125.2, 84.0, 83.2, 80.3, 49.2, 47.0, 32.3, 24.7, 24.6.

[0765] Minor: 1 H NMR (CDCl 3 ​, 400 MHz): δ 7.90 - 7.78 (m, 3H), 7.64 (s, 1H), 7.51 - 7.40 (m, 3H), 4.82 (d, J = 6.8 Hz, 1H), 4.70 (d, J = 6.8 Hz, 1H), 4.43 (d, J = 6.4 Hz, 1H), 4.39 (d, J = 6.4 Hz, 1H), 3.72 (d, J = 9.6 Hz, 1H), 2.43 - 2.24 (m, 2H), 2.03 (q, J = 9.5 Hz, 1H), 1.24 (s, 12H).

[0766] 13 C NMR(CDCl 3 , 100 MHz): δ 138.7, 133.6, 132.3, 128.1, 127.7, 127.6, 126.0, 125.8, 125.44, 125.41, 83.4, 82.6, 79.7, 48.5, 48.1, 31.5, 24.75, 24.68.

[0767] HRMS(EI) calculated for [C 22 H 27 BO 3 + requires m / z 350.2048, found m / z 350.2052.

[0768]

[0769] 5-(Naphthalen-2-yl)-6,6-diphenyl-2-oxaspiro[3.3]heptane (86). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and styrene (68 μL, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to afford 58.9 mg (0.196 mmol, 98% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0770] 1 H NMR(CDCl 3 ​, 400 MHz): δ 7.92 - 7.78 (m, 1.20H), 7.72 - 7.64 (m, 1.60H), 7.56 - 7.44 (m, 1.80H), 7.42 - 7.34 (m, 1.80H), 7.30 - 7.17 (m, 2H), 7.09 - 7.01 (m, 1.20H), 7.00 - 6.94 (m, 0.60H), 6.93 - 6.85 (m, 1.80H), 5.04 (d, J = 6.0 Hz, 0.60H), 4.97 (d, J = 6.0 Hz, 0.60H), 4.85 (d, J = 6.7 Hz, 0.40H), 4.74 (d, J = 6.7 Hz, 0.40H), 4.62 - 4.50 (m, 1.40H), 4.44 (d, J = 6.9 Hz, 0.60H), 4.21 - 4.15 (m, 0.60H), 4.10 - 3.98 (m, 0.60H), 3.82 - 3.67 (m, 0.80H), 3.07 - 2.98 (m, 0.60H), 2.92 - 2.83 (m, 0.60H), 2.80 - 2.70 (m, 0.40H), 2.45 - 2.31 (m, 0.40H).

[0771] 13 C NMR(CDCl 3 , 100 MHz): δ 143.6, 140.2, 137.1, 135.7, 133.5, 133.2, 132.5, 131.9, 128.5, 128.4, 127.8, 127.72, 127.71, 127.66, 127.6, 127.5, 127.4, 127.2, 126.8, 126.4, 126.2, 125.9, 125.82, 125.78, 125.7, 125.6, 125.3, 85.3, 81.4, 79.4, 79.2, 55.2, 53.8, 44.9, 43.6, 38.9, 38.4, 37.2, 36.7.

[0772] HRMS(EI) calculated for [C 22 H 20 O] + requires m / z 300.1509, found m / z 300.1508.

[0773]

[0774] 5-(Naphthalen-2-yl)-6-(p-tolyl)-2-oxaspiro[3.3]heptane (87). The title compound was synthesized according to General Procedure C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-methyl-4-vinylbenzene (77 μL, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to afford 57.2 mg (0.182 mmol, 91% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0775] 1 H NMR(CDCl 3 , 400 MHz): δ 7.91 - 7.76 (m, 1.20H), 7.72 - 7.63 (m, 1.60H), 7.54 (d, J = 8.5 Hz, 0.60H), 7.51 - 7.33 (m, 3H), 7.16 - 7.05 (m, 1.60H), 6.90 (dd, J = 8.5, 1.8 Hz, 0.60H), 6.85 (d, J = 8.0 Hz, 1.20H), 6.78 (d, J = 8.0 Hz, 1.20H), 5.02 (d, J = 5.9 Hz, 0.60H), 4.96 (d, J = 6.0 Hz, 0.60H), 4.84 (d, J = 6.7 Hz, 0.40H), 4.73 (d, J = 6.7 Hz, 0.40H), 4.61 - 4.50 (m, 1.40H), 4.44 (d, J = 6.9 Hz, 0.60H), 4.14 (dd, J = 9.3, 3.0 Hz, 0.60H), 3.99 (q, J = 9.4 Hz, 0.60H), 3.77 - 3.62 (m, 0.80H), 3.03 - 2.95 (m, 0.60H), 2.89 - 2.80 (m, 0.60H), 2.78 - 2.69 (m, 0.40H), 2.37 - 2.28 (m, 1.60H), 2.14 (s, 1.80H).

[0776] 13 C NMR(CDCl 3, 100 MHz): δ 140.5, 137.2, 137.1, 135.9, 135.0, 133.5, 133.3, 132.5, 131.9, 129.1, 128.5, 128.4, 127.70, 127.68, 127.64, 127.60, 127.5, 127.4, 127.1, 126.9, 126.3, 126.1, 125.9, 125.8, 125.7, 125.6, 125.3, 85.3, 81.5, 79.4, 79.2, 55.1, 53.9, 44.9, 43.6, 38.7, 38.2, 37.4, 36.9, 21.0, 20.9。

[0777] HRMS(EI) calculation for [C 23 H 22 O] + requires m / z 314.1665, found m / z 314.1665.

[0778]

[0779] 5-(Naphthalen-2-yl)-6-(4-(trifluoromethyl)phenyl)-2-oxaspiro[3.3]heptane (88). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-(trifluoromethyl)-4-vinylbenzene (103 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (8:1 v / v) as the eluent to afford 60.4 mg (0.164 mmol, 82% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0780] Major: 1 H NMR (CDCl 3 , 400 MHz): δ 7.94 - 7.80 (m, 3H), 7.71 - 7.66 (m, 1H), 7.57 - 7.44 (m, 5H), 7.36 - 7.29 (m, 2H), 4.85 (d, J = 6.8 Hz, 1H), 4.74 (d, J = 6.8 Hz, 1H), 4.60 (d, J = 6.2 Hz, 1H), 4.53 (d, J = 6.2 Hz, 1H), 3.88 - 3.67 (m, 2H), 2.88 - 2.76 (m, 1H), 2.46 - 2.29 (m, 1H).

[0781] 19 F NMR (CDCl 3 , 376 MHz): δ -62.38.

[0782] 13 C NMR (CDCl 3 , 100 MHz): δ 147.6, 136.4, 133.5, 132.6, 130.9, 128.68 (q, J=32.3 Hz), 128.66, 127.7, 126.7, 126.4, 125.90, 125.86, 125.6, 125.4 (q, J=3.7 Hz), 124.2 (q, J=270.2 Hz), 81.2, 79.0, 53.8, 45.0, 38.3, 37.0。

[0783] Minor: 1 H NMR (CDCl 3 , 400 MHz): δ 7.74 - 7.66 (m, 2H), 7.55 (d, J=8.6 Hz, 1H), 7.46 - 7.37 (m, 3H), 7.30 (d, J=8.0 Hz, 2H), 7.00 (d, J=8.0 Hz, 2H), 6.85 (dd, J=8.6, 1.8 Hz, 1H), 5.05 (d, J=6.0 Hz, 1H), 4.98 (d, J=6.0 Hz, 1H), 4.55 (d, J=7.0 Hz, 1H), 4.43 (d, J=7.0 Hz, 1H), 4.24 - 4.20 (m, 1H), 4.11 - 4.06 (m, 1H), 3.09 - 2.90 (m, 2H)。

[0784] 19 F NMR (CDCl 3 , 376 MHz): δ - 62.36。

[0785] 13 C NMR (CDCl 3 , 100 MHz): δ 144.6, 135.1, 133.3, 132.0, 127.9 (q, J=18.2 Hz), 127.9, 127.8, 127.54, 127.53, 127.4, 126.4, 126.1, 125.6, 124.8 (q, J=3.8 Hz), 124.1 (q, J=272.0 Hz), 85.1, 79.3, 55.2, 43.6, 38.8, 36.9。

[0786] HRMS (EI) calculated for [C 23 H 19 F 3 O] + requires m / z 368.1383, found m / z 368.1374。

[0787]

[0788] 6-(4-Chlorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (89). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-chloro-4-vinylbenzene (83.2 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to give 58.8 mg (0.176 mmol, 88% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0789] Major: 1 H NMR(CDCl 3 , 400 MHz): δ 7.95 - 7.81 (m, 3H), 7.71 (s, 1H), 7.56 - 7.46 (m, 3H), 7.31 - 7.24 (m, 2H), 7.20 - 7.15 (m, 2H), 4.87 (d, J = 6.8 Hz, 1H), 4.77 (d, J = 6.8 Hz, 1H), 4.62 (d, J = 6.2 Hz, 1H), 4.55 (d, J = 6.2 Hz, 1H), 3.81 - 3.61 (m, 2H), 2.85 - 2.76 (m, 1H), 2.42 - 2.31 (m, 1H).

[0790] 13 C NMR(CDCl 3 , 100 MHz): δ 142.0, 136.7, 133.5, 132.6, 132.1, 128.6, 128.5, 127.74, 127.70, 126.3, 125.9, 125.8, 125.7, 81.3, 79.1, 53.9, 45.0, 38.0, 37.2.

[0791] Minor: 1 H NMR(CDCl 3 , 400 MHz): δ 7.74 - 7.65 (m, 2H), 7.56 (d, J = 8.4 Hz, 1H), 7.46 - 7.35 (m, 3H), 7.03 - 6.97 (m, 2H), 6.89 - 6.78 (m, 3H), 5.03 (d, J = 6.0 Hz, 1H), 4.97 (d, J = 6.0 Hz, 1H), 4.55 (d, J = 6.8 Hz, 1H), 4.44 (d, J = 6.8 Hz, 1H), 4.17 (dd, J = 9.2, 3.2 Hz, 1H), 3.99 (q, J = 9.4 Hz, 1H), 3.04 - 2.94 (m, 1H), 2.93 - 2.81 (m, 1H).

[0792] 13 C NMR(CDCl 3 , 100 MHz): δ 138.8, 135.4, 133.2, 132.0, 131.4, 128.5, 127.9, 127.8, 127.7, 127.6, 127.5, 126.6, 126.0, 125.5, 85.2, 79.3, 55.2, 43.5, 38.4, 36.9.

[0793] HRMS(EI) calcd for [C 22 H 19 ClO] + requires m / z 334.1119, found m / z 334.1112.

[0794]

[0795] 6-(4-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (90). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-4-vinylbenzene (73.3 mg, 0.6 mmol) according to General Procedure C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (8:1 v / v) as the eluent to afford 63.1 mg (0.198 mmol, 99% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0796] 1 H NMR(CDCl 3, 400 MHz): δ 7.90 - 7.65 (m, 3H), 7.54 (d, J = 8.4 Hz, 0.57H), 7.49 - 7.43 (m, 1.14H), 7.43 - 7.35 (m, 1.43H), 7.20 - 7.13 (m, 0.86H), 6.99 - 6.68 (m, 4H), 5.03 (d, J = 6.0 Hz, 0.57H), 4.96 (d, J = 6.0 Hz, 0.57H), 4.83 (d, J = 6.8 Hz, 0.43H), 4.72 (d, J = 6.8 Hz, 0.43H), 4.61 - 4.54 (m, 1H), 4.51 (d, J = 6.2 Hz, 0.43H), 4.46 (d, J = 6.9 Hz, 0.57H), 4.14 (dd, J = 9.4, 3.0 Hz, 0.57H), 3.98 (q, J = 9.5 Hz, 0.57H), 3.75 - 3.61 (m, 0.86H), 3.03 - 2.93 (m, 0.57H), 2.91 - 2.81 (m, 0.57H), 2.80 - 2.71 (m, 0.43H), 2.43 - 2.17 (m, 0.43H).

[0797] 19 F NMR(CDCl 3 , 376 MHz): δ -116.6, -117.3.

[0798] 13 C NMR(CDCl 3 , 100 MHz): δ 161.4 (d, J = 244.4 Hz), 160.9 (d, J = 243.9 Hz), 139.2 (d, J = 3.3 Hz), 136.7, 135.9 (d, J = 3.2 Hz), 135.5, 133.5, 133.2, 132.5, 131.9, 128.6, 128.5, 127.8 (d, J = 7.9 Hz), 127.7, 127.5 (d, J = 6.0 Hz), 126.7, 126.2, 125.90, 125.87, 125.7, 125.5, 115.2 (d, J = 21.2 Hz), 114.6 (d, J = 21.2 Hz), 85.2, 81.3, 79.3, 79.1, 55.2, 54.0, 44.9, 43.4, 38.3, 37.8, 37.3, 37.0.

[0799] HRMS(EI) calculated for [C 22 H 19 FO] + requires m / z 318.1414, found m / z 318.1407.

[0800]

[0801] 6-(3-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (91). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-3-vinylbenzene (73.5 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (8:1 v / v) as the eluent to afford 59.2 mg (0.186 mmol, 93% yield, 1.4:1 d.r.) of the title compound as a colorless oil.

[0802] 1 H NMR(CDCl 3 , 400 MHz): δ 7.93 - 7.79 (m, 1.29H), 7.73 - 7.61 (m, 1.57H), 7.55 (d, J = 8.5 Hz, 0.57H), 7.48 - 7.36 (m, 2.43H), 7.25 - 7.17 (m, 0.57H), 7.03 - 6.81 (m, 2.86H), 6.72 - 6.56 (m, 1.71H), 5.02 (d, J = 6.0 Hz, 0.57H), 4.96 (d, J = 6.0 Hz, 0.57H), 4.83 (d, J = 6.8 Hz, 0.43H), 4.72 (d, J = 6.8 Hz, 0.43H), 4.60 - 4.48 (m, 1.43H), 4.43 (d, J = 6.9 Hz, 0.57H), 4.16 (dd, J = 9.3, 3.0 Hz, 0.57H), 4.01 (q, J = 9.5 Hz, 0.57H), 3.79 - 3.64 (m, 0.86H), 3.04 - 2.94 (m, 0.57H), 2.91 - 2.82 (m, 0.57H), 2.82 - 2.65 (m, 0.43H), 2.42 - 2.27 (m, 0.43H).

[0803] 19 F NMR(CDCl 3 , 376 MHz): δ -113.1, -113.8.

[0804] 13 C NMR(CDCl 3, 100 MHz): δ 162.9 (d, J = 246.0 Hz), 162.6 (d, J = 245.3 Hz), 146.2 (d, J = 7.0 Hz), 143.0 (d, J = 7.1 Hz), 136.6, 135.3, 133.5, 133.2, 132.6, 132.0, 129.9 (d, J = 8.4 Hz), 129.2 (d, J = 8.3 Hz), 128.6, 127.71, 127.68, 127.6, 127.5, 126.5, 126.3, 125.90, 125.88, 125.8, 125.7, 125.5, 122.9 (d, J = 2.8 Hz), 122.0 (d, J = 2.7 Hz), 114.1 (d, J = 21.3 Hz), 113.3 (d, J = 21.0 Hz), 113.2 (d, J = 21.0 Hz), 112.5 (d, J = 21.1 Hz), 85.1, 81.3, 79.3, 79.0, 55.2, 53.8, 44.9, 43.5, 38.7 (d, J = 1.8 Hz), 38.2 (d, J = 1.8 Hz), 37.1, 36.7。

[0805] HRMS (EI) calculated for [C 22 H 19 FO] + requires m / z 318.1414, found m / z 318.1415.

[0806]

[0807] 6-(2-Fluorophenyl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (92). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1-fluoro-2-vinylbenzene (73.1 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (8:1 v / v) as the eluent to afford 59.7 mg (0.188 mmol, 94% yield, 1.5:1 d.r.) of the title compound as a colorless oil.

[0808] 1 H NMR (CDCl 3, 400 MHz): δ 7.90 - 7.78 (m, 1.20H), 7.71 - 7.63 (m, 1.60H), 7.56 - 7.43 (m, 1.80H), 7.41 - 7.31 (m, 1.80H), 7.27 - 7.21 (m, 0.60H), 7.20 - 7.11 (m, 0.40H), 7.07 - 6.84 (m, 3H), 6.71 - 6.64 (m, 0.60H), 5.06 (d, J = 6.0 Hz, 0.60H), 4.98 (d, J = 6.0 Hz, 0.60H), 4.87 (d, J = 6.8 Hz, 0.40H), 4.75 (d, J = 6.8 Hz, 0.40H), 4.62 - 4.56 (m, 1H), 4.51 (d, J = 6.3 Hz, 0.40H), 4.47 (d, J = 6.9 Hz, 0.60H), 4.25 - 4.19 (m, 0.60H), 4.19 - 4.08 (m, 0.60H), 3.96 - 3.80 (m, 0.80H), 3.16 - 3.04 (m, 0.60H), 2.86 - 2.76 (m, 1H), 2.46 - 2.24 (m, 0.40H).

[0809] 19 F NMR(CDCl 3 , 376 MHz): δ -115.3, -116.9.

[0810] 13 C NMR(CDCl 3, 100 MHz): δ 160.9 (d, J = 245.3 Hz), 160.6 (d, J = 245.1 Hz), 136.6, 135.6, 133.5, 133.2, 132.5, 131.9, 129.9 (d, J = 15.5 Hz), 128.4, 128.0, 127.90, 127.89 (d, J = 7.2 Hz), 127.88, 127.7, 127.64, 127.63 (d, J = 8.2 Hz), 127.61, 127.4 (d, J = 7.3 Hz), 127.3, 127.2, 127.1, 126.4, 126.2, 125.8 (d, J = 4.7 Hz), 125.7, 125.6 (d, J = 4.0 Hz), 125.3, 124.1 (d, J = 3.5 Hz), 123.4 (d, J = 3.4 Hz), 115.3 (d, J = 22.0 Hz), 114.6 (d, J = 21.5 Hz), 85.3, 81.4, 79.5, 79.1, 55.3 (d, J = 1.3 Hz), 52.5, 45.3, 43.7, 37.2 (d, J = 2.0 Hz), 35.4, 34.4 (d, J = 1.6 Hz), 32.9 (d, J = 1.6 Hz).

[0811] HRMS (EI) calculation for [C 22 H 19 FO] + requires m / z 318.1414, found m / z 318.1406.

[0812]

[0813] trans-2-(5-(Naphthalen-2-yl)-2-oxaspiro[3.3]heptan-6-yl)pyridine (93). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 2-vinylpyridine (63 μL, 0.6 mmol). According to 1 1H NMR analysis, the diastereomeric ratio of the trans and cis products in the crude reaction mixture was determined to be 1.1:1. The mixture was then purified by flash column chromatography using hexane / ethyl acetate (5:1 → 2:1 v / v) as the eluent to give 54.2 mg (0.180 mmol, 90% yield, >10:1 d.r.) of the title compound as a colorless oil.

[0814] 1 1H NMR (CDCl 3, 400 MHz): δ 8.59 (d, J = 4.4 Hz, 1H), 7.90 - 7.78 (m, 3H), 7.71 (s, 1H), 7.57 (td, J = 7.6, 1.8 Hz, 1H), 7.51 - 7.42 (m, 3H), 7.19 (d, J = 7.6 Hz, 1H), 7.15 - 7.09 (m, 1H), 4.90 (d, J = 6.8 Hz, 1H), 4.79 (d, J = 6.8 Hz, 1H), 4.60 (d, J = 6.2 Hz, 1H), 4.54 (d, J = 6.2 Hz, 1H), 4.02 (d, J = 9.8 Hz, 1H), 3.88 - 3.74 (m, 1H), 2.79 - 2.59 (m, 2H).

[0815] 13 C NMR(CDCl 3 , 100 MHz): δ 161.7, 149.6, 137.0, 136.4, 133.5, 132.5, 128.4, 127.69, 127.66, 126.2, 125.812, 125.807, 125.6, 121.9, 121.7, 81.7, 79.2, 52.6, 44.9, 40.9, 36.2.

[0816] HRMS(EI) calculated for [C 21 H 19 NO] + requires m / z 301.1461, found m / z 301.1467.

[0817]

[0818] 1 - Methyl - 5-(5-(naphthalen - 2 - yl)-2 - oxaspiro[3.3]hept - 6 - yl)-1H - indole (94). The title compound was synthesized using 3-(naphthalen - 2 - ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 1 - methyl - 5 - vinyl - 1H - indole (94.3 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 → 5:1 v / v) as the eluent to give 65.6 mg (0.186 mmol, 93% yield, 1.2:1 d.r.) of the title compound as a colorless oil.

[0819] 1 H NMR(CDCl 3, 400 MHz): δ 7.89 - 7.77 (m, 1.45H), 7.74 (s, 0.45H), 7.68 - 7.58 (m, 1.10H), 7.54 - 7.40 (m, 3H), 7.38 - 7.29 (m, 1.10H), 7.24 - 7.16 (m, 0.90H), 7.10 (d, J = 8.4 Hz, 0.45H), 7.01 - 6.83 (m, 2H), 6.68 (d, J = 8.4 Hz, 0.55H), 6.38 (d, J = 3.2 Hz, 0.45H), 6.29 (d, J = 3.2 Hz, 0.55H), 5.04 (d, J = 6.0 Hz, 0.55H), 4.98 (d, J = 6.0 Hz, 0.55H), 4.86 (d, J = 6.8 Hz, 0.45H), 4.75 (d, J = 6.8 Hz, 0.45H), 4.63 - 4.51 (m, 1.45H), 4.44 (d, J = 6.8 Hz, 0.55H), 4.21 - 4.09 (m, 1.10H), 3.85 - 3.75 (m, 0.90H), 3.70 (s, 1.35H), 3.56 (s, 1.65H), 3.13 - 3.03 (m, 0.55H), 2.95 - 2.85 (m, 0.55H), 2.83 - 2.74 (m, 0.45H), 2.51 - 2.30 (m, 0.45H).

[0820] 13 C NMR(CDCl 3 , 100 MHz): δ 137.5, 136.3, 135.5, 135.1, 134.5, 133.7, 133.2, 132.4, 131.8, 131.1, 129.2, 128.54, 128.48, 128.3, 128.1, 127.7, 127.62, 127.57, 127.4, 127.0, 126.02, 125.97, 125.9, 125.6, 125.5, 125.1, 121.4, 120.4, 118.7, 118.0, 109.1, 108.6, 100.6, 100.4, 85.4, 81.6, 79.5, 79.4, 55.3, 54.2, 44.8, 43.7, 39.1, 38.7, 38.0, 37.2, 32.8, 32.6.

[0821] HRMS(EI) calculated for [C 25 H 23 NO] + requires m / z 353.1774, found m / z 353.1773.

[0822]

[0823] 5-(5-(Naphthalen-2-yl)-2-oxaspiro[3.3]hept-6-yl)benzofuran (95). The title compound was synthesized using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 5-vinylbenzofuran (86.5 mg, 0.6 mmol) according to General Method C. The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 → 5:1 v / v) as the eluent to give 62.6 mg (0.184 mmol, 92% yield, 1.0:1 d.r.) of the title compound as a colorless oil.

[0824] 1 H NMR(CDCl 3 , 400 MHz): δ 7.94 - 7.75 (m, 1.50H), 7.73 (s, 0.50H), 7.69 - 7.62 (m, 1H), 7.56 (d, J = 2.3 Hz, 0.50H), 7.51 - 7.32 (m, 5H), 7.20 - 7.10 (m, 1.50H), 6.89 (dd, J = 8.4, 1.8 Hz, 0.50H), 6.78 (d, J = 8.4 Hz, 0.50H), 6.66 (d, J = 2.4 Hz, 0.50H), 6.55 (d, J = 2.4 Hz, 0.50H), 5.05 (d, J = 6.0 Hz, 0.50H), 4.98 (d, J = 6.0 Hz, 0.50H), 4.85 (d, J = 6.8 Hz, 0.50H), 4.74 (d, J = 6.8 Hz, 0.50H), 4.60 (d, J = 6.2 Hz, 0.50H), 4.58 - 4.51 (m, 1H), 4.44 (d, J = 6.8 Hz, 0.50H), 4.22 - 4.07 (m, 1H), 3.90 - 3.70 (m, 1H), 3.11 - 3.02 (m, 0.50H), 2.95 - 2.87 (m, 0.50H), 2.84 - 2.77 (m, 0.50H), 2.43 - 2.32 (m, 0.50H).

[0825] 13 C NMR(CDCl 3, 100 MHz): δ 153.7, 153.3, 145.3, 144.8, 138.2, 137.1, 135.8, 134.8, 133.6, 133.2, 132.5, 131.9, 128.5, 127.72, 127.71, 127.66, 127.53, 127.48, 127.4, 127.0, 126.8, 126.2, 125.93, 125.86, 125.8, 125.7, 125.3, 123.8, 122.8, 119.2, 118.5, 111.2, 110.6, 106.40, 106.36, 85.3, 81.4, 79.4, 79.2, 55.3, 54.2, 44.9, 43.5, 38.9, 38.4, 37.7, 37.2。

[0826] HRMS (EI) calculation for [C 24 H 20 O 2 + requires m / z 340.1458, found m / z 340.1452.

[0827]

[0828] 6-(Benzo[b]thiophen-5-yl)-5-(naphthalen-2-yl)-2-oxaspiro[3.3]heptane (96). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and 5-vinylbenzo[b]thiophene (96.0 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane / ethyl acetate (10:1 → 5:1 v / v) as the eluent to give 62.8 mg (0.176 mmol, 88% yield, 1.0:1 d.r.) of the title compound as a colorless oil.

[0829] 1 H NMR (CDCl 3 ​, 400 MHz): δ 7.91 - 7.72 (m, 2.50H), 7.68 - 7.57 (m, 1.50H), 7.53 - 7.31 (m, 5H), 7.28 (d, J = 5.4 Hz, 0.50H), 7.23 - 7.18 (m, 1H), 7.13 (d, J = 5.4 Hz, 0.50H), 6.90 (dd, J = 8.4, 1.8 Hz, 0.50H), 6.81 (d, J = 8.4 Hz, 0.50H), 5.05 (d, J = 6.0 Hz, 0.50H), 4.98 (d, J = 6.0 Hz, 0.50H), 4.86 (d, J = 6.8 Hz, 0.50H), 4.74 (d, J = 6.8 Hz, 0.50H), 4.60 (d, J = 6.4 Hz, 0.50H), 4.57 - 4.52 (m, 1H), 4.43 (d, J = 6.8 Hz, 0.50H), 4.23 - 4.09 (m, 1H), 3.89 - 3.73 (m, 1H), 3.17 - 3.04 (m, 0.50H), 2.98 - 2.88 (m, 0.50H), 2.84 - 2.73 (m, 0.50H), 2.45 - 2.30 (m, 0.50H).

[0830] 13 C NMR(CDCl 3 , 100 MHz): δ 139.8, 139.4, 137.8, 137.1, 137.0, 136.6, 135.7, 133.5, 133.2, 132.5, 131.9, 128.5, 127.8, 127.71, 127.66, 127.6, 127.5, 127.4, 126.8, 126.7, 126.20, 126.18, 125.9, 125.82, 125.78, 125.7, 125.3, 124.1, 123.62, 123.60, 123.2, 122.4, 121.74, 121.65, 120.9, 85.3, 81.4, 79.4, 79.2, 55.2, 54.0, 44.9, 43.6, 38.9, 38.4, 37.5, 37.1.

[0831] HRMS(EI) calculated [C 24 H 20 OS] + requires m / z 356.1229, found m / z 356.1227.

[0832]

[0833] 5-(Naphthalen-2-yl)-6,6-diphenyl-2-oxaspiro[3.3]heptane (97). The title compound was synthesized according to General Method C using 3-(naphthalen-2-ylmethylene)oxetane (39.2 mg, 0.2 mmol) and ethene-1,1-diyl dibenzene (108 mg, 0.6 mmol). The crude mixture was purified by flash column chromatography using hexane to hexane / ethyl acetate (20:1 v / v) as the eluent to afford 62.5 mg (0.166 mmol, 83% yield) of the title compound as a colorless oil.

[0834] 1 H NMR(CDCl 3 , 400 MHz): δ 7.77 - 7.64 (m, 2H), 7.57 (d, J = 8.4 Hz, 1H), 7.46 - 7.37 (m, 5H), 7.33 - 7.27 (m, 2H), 7.20 - 7.11 (m, 1H), 7.07 - 6.98 (m, 3H), 6.97 - 6.91 (m, 2H), 6.81 (dd, J = 8.4, 2.0 Hz, 1H), 4.72 - 4.65 (m, 2H), 4.62 (d, J = 6.4 Hz, 1H), 4.55 (d, J = 6.8 Hz, 2H), 3.64 (d, J = 12.6 Hz, 1H), 3.16 (dd, J = 12.6, 2.1 Hz, 1H).

[0835] 13 C NMR(CDCl 3 , 100 MHz): δ 150.3, 144.1, 135.6, 133.2, 132.2, 129.0, 128.4, 127.9, 127.74, 127.72, 127.44, 127.41, 127.37, 126.2, 125.89, 125.87, 125.7, 125.6, 83.9, 79.2, 59.9, 52.5, 43.8, 43.7.

[0836] HRMS(EI) calcd for [C 28 H 24 O] + requires m / z 376.1822, found m / z 376.1812.

[0837] Stability studies of Cu-2 and UiO-69-phen(binap)Cu

[0838]

[0839] Cu-2 (2 μmol, 2.8 mg), 4-dimethylaminopyridine (0.01 mmol, 5.0 equiv), and 1,2-dichloroethane (1.0 mL) were added to a cooled 25 mL direct-fire dried Schlenk flask under N 2 at. After three freeze-thaw pump cycles, the reaction was irradiated at room temperature for 24 h with three 40 W Kessil PR160L-440 blue LED lights (with three fans). Then, 1,2-dichloroethane was removed in vacuo and 0.6 mL of CDCl 3 . The resulting mixture was analyzed by 1 H NMR and 31 P NMR. The NMR spectra showed that Cu-2 had been completely degraded; 31 only the signal of phosphine oxide was detected by

[0840]

[0841] UiO-69-phen(binap)Cu (2 μmol based on Cu, 11.9 mg), 4-dimethylaminopyridine (0.01 mmol, 5.0 equiv), and 1,2-dichloroethane (1.0 mL) were added to a cooled 25 mL direct-fire dried Schlenk flask under N 2 at. After three freeze-thaw pump cycles, the reaction was irradiated at room temperature for 24 h with three 40 W Kessil PR160L-440 blue LED lights (with three fans). After irradiation, the solid was collected by filtration and washed with 1,2-dichloroethane. 2 mg of the dried solid was dissolved in a D 3 PO 4 / D 2 O / DMSO-d 6 (1:1:5 v / v / v) solution and 1 H NMR analysis was performed. According to the 1 H NMR spectrum, the ratio of Cu-2 to L3 was found to be 1:5.

[0842] Recovery experiment:

[0843] UiO-69-phen(binap)Cu (2 μmol based on Cu, 11.9 mg), 4-dimethylaminopyridine (0.01 mmol, 5.0 equiv), and 1,2-dichloroethane (1.0 mL) were added to a cooled 25 mL direct-fire dried Schlenk flask under N 2Under an inert atmosphere, UiO-69-phen(binap)Cu (5.9 mg, 1 μmol based on Cu, 0.5 mol %), 4-dimethylaminopyridine (29 mg, 0.24 mmol, 1.2 equiv), 1,2-dichloroethane (1.0 mL), 1-vinylnaphthalene (30.8 mg, 0.2 mmol), and acrylonitrile (66 μL, 1.0 mmol) were successively added to a cooled 25 mL direct-fire drying Schlenk tube. After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (equipped with three fans) for 48 hours. After irradiation, UiO-69-phen(binap)Cu was recovered by filtration and washed with anhydrous 1,2-dichloroethane (3 × 10 mL) for subsequent photocatalytic reactions. The filtrate was concentrated under vacuum and used for 1 1H NMR analysis to determine the yield. The above operation was repeated six times.

[0844] Mechanism study:

[0845] Triplet excited state quenching experiment

[0846]

[0847] The reaction was carried out according to General Method A, using trans-stilbene as a triplet energy transfer inhibitor. After irradiation, using phenyltrimethylsilane as an internal standard, the yield of 23 was determined by crude 1 1H NMR.

[0848] The required intermolecular cross-ring cycloaddition was completely inhibited.

[0849]

[0850] The reaction was carried out according to General Method C, using trans-stilbene as a triplet energy transfer inhibitor. After irradiation, using phenyltrimethylsilane as an internal standard, the yield of 70 was determined by crude 1 1H NMR. The required intermolecular cross-ring cycloaddition was completely inhibited.

[0851] Intermolecular cross-[2+2] cycloaddition kinetics study:

[0852] For the reaction with styrene (2.0 M): To the reaction system in N 2Under an inert atmosphere, 4-phenylmorpholine (39.2 mg, 0.24 mmol), acrylonitrile (132 μL, 2.0 mmol), and styrene (0.40 mmol) were successively added to a cooled 25 mL direct-fire drying Schlenk tube. The mixture was diluted to a total volume of 0.2 mL with 1,2-dichloroethane to obtain a homogeneous solution with a styrene concentration of 2.0 M. Then UiO-69-phen(binap)Cu (35.6 mg, 6 μmol based on Cu, 1.5 mol%) was added. After three freeze-thaw pump cycles, the reaction mixture was irradiated at room temperature with three 40-watt Kessil PR160L-440 blue LED lights (with three fans). 30 μL of the reaction mixture was taken out after 10, 24, 29, 34, and 48 hours, respectively. After removing the solvent under vacuum, 0.8 mL of phenyltrimethylsilane solution (0.05 M, in CDCl 3 3) was added to the residue, and the sample was subjected to 1 1H NMR analysis using phenyltrimethylsilane as the internal standard.

[0853] For the reaction with styrene (1.5 M): The procedure was the same as described above, except that 0.30 mmol of styrene was added to the reaction.

[0854] For the reaction with styrene (1.0 M): The procedure was the same as described above, except that 0.20 mmol of styrene was added to the reaction.

[0855] For the reaction with styrene (0.5 M): The procedure was the same as described above, except that 0.10 mmol of styrene was added to the reaction.

[0856] For the reaction with styrene (0.2 M): The procedure was the same as described above, except that 0.04 mmol of styrene was added to the reaction.

[0857] The molar concentration of product 16 was calculated based on the 1 1H NMR integration with reference to the internal standard. At each time point, the data represent the average of two identical experiments. The molar concentration of product 16 was plotted against the reaction time to obtain a typical reaction kinetic curve. The reaction rate was calculated by measuring the accumulation of product 16 from 10 to 24 hours.

[0858] References (cited in the additional detailed information of Example 1 above):

[0859] 1. Zhang, X., et al. Catalytic chemoselective functionalization of methane in a metal-organic framework. Nat. Catal. 1, 356 - 362 (2018).

[0860] 2. Murray, P. R. D., et al. Intermolecular crossed [2+2] cycloaddition promoted by visible-light triplet photosensitization: expedient access to polysubstituted 2-oxaspiro[3.3]heptanes. J. Am. Chem. Soc. 143, 4055 - 4063 (2021).

[0861] 3. Wu, X.-H., et al. NH 4 Cl-induced low-temperature formation of nitrogen-rich g-C 3 N 4 nanosheets with improved photocatalytic hydrogen evolution. Carbon 153, 757 - 766 (2019).

[0862] 4. Ho, W. H., et al. Proton-conductive cerium-based metal-organic frameworks. ACS Appl. Mater. Interfaces 13, 55358 - 55366 (2021).

[0863] 5. Chen, H., Wang, L.-F., Wang, J. & Yang, R. T. Investigation on hydrogenation of metal-organic frameworks HKUST-1, MIL-53, and ZIF-8 by hydrogen spillover. J. Phys. Chem. C 117, 7565 - 7576 (2013).

[0864] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed invention pertains. Publications and materials cited herein are specifically incorporated by reference.

[0865] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

1. A heterogeneous catalyst comprising: a metal-organic framework formed from a plurality of inorganic nodes and a plurality of organic linkers, wherein at least one organic linker of the plurality of organic linkers comprises a phenanthroline moiety; At least one copper (I) ion is attached to the phenanthroline moiety and to a phosphine ligand to form a catalyst complex within the metal organic framework.

2. The heterogeneous catalyst of claim 1, wherein the phosphine ligand has the following chemical structure: wherein Rq and Rq' are each independently selected from hydrogen, alkyl, alkoxy or aryl; and wherein each Ar is independently selected from a phenyl group or an aromatic group; optionally, wherein the aromatic group is wherein each Alk is independently an alkyl group. 3 . The heterogeneous catalyst of claim 1 , wherein the phosphine ligand is 2,2′-bis(diphenylphosphine)-1,1′-binaphthyl (binap).

4. The heterogeneous catalyst of claim 1, wherein the plurality of inorganic nodes comprises [Zr6] inorganic nodes.

5. The heterogeneous catalyst of claim 1, wherein the plurality of organic linkers comprises a quaternary dicarboxylic acid organic linker; optionally, wherein the quaternary dicarboxylic acid organic linker comprises one or more tetramethyl-substituted quaternary dicarboxylic acid organic linkers, and optionally, the tetramethyl-substituted quaternary group is 2',2",5',5"-tetramethyl-[1,1':4',1":4",1"'-quaternary]-4,4"'-dicarboxylic acid.

6. The heterogeneous catalyst of claim 1, wherein at least one of the plurality of organic linkers comprising the phenanthroline moiety is derived from 4,4'-(1,10-phenanthroline-3,8-diyl)dibenzoic acid.

7. The heterogeneous catalyst of claim 1, wherein the metal organic framework is a Universitetet Oslo-69 metal organic framework.

8. The heterogeneous catalyst of claim 1, wherein the catalyst complex comprises the following chemical structure:

9. A method for synthesizing the heterogeneous catalyst according to claim 1, comprising the following steps: (i) reacting a plurality of organic linkers with an inorganic salt to form a metal-organic framework comprising a plurality of inorganic nodes, wherein at least one of the plurality of organic linkers comprises a phenanthroline moiety; (ii) metallizing the metal organic framework by mixing a metal complex comprising at least one copper(I) ion linked to a phosphine ligand with the metal organic framework; wherein the metallating step comprises causing the at least one copper (I) ion to become attached to the phenanthroline moiety to form a catalyst complex within the metal organic framework.

10. A method for synthesizing the heterogeneous catalyst according to claim 1, comprising the following steps: (i') metallizing the metal organic framework by mixing a metal complex comprising at least one copper(I) ion linked to a phosphine ligand with the metal organic framework; wherein the metal organic framework is formed by a plurality of inorganic nodes and a plurality of organic linkers, wherein at least one organic linker of the plurality of organic linkers comprises a phenanthroline moiety; wherein the metallating step comprises causing the at least one copper (I) ion to become attached to the phenanthroline moiety to form a catalyst complex within the metal organic framework.

11. The method of claim 9, wherein the phosphine ligand has the following chemical structure: wherein Rq and Rq' are each independently selected from hydrogen, alkyl, alkoxy or aryl; and wherein each Ar is independently selected from a phenyl group or an aromatic group; optionally, wherein the aromatic group is wherein each Alk is independently an alkyl group.

12. The method of claim 9, wherein the plurality of inorganic nodes comprises [Zr6] inorganic nodes.

13. The method of claim 9, wherein the plurality of organic linkers comprises a quatrefoil organic linker; optionally, wherein the quatrefoil organic linker comprises one or more tetramethyl-substituted quatrefoil organic linkers, and optionally, the tetramethyl-substituted quatrefoil is 2',2",5',5"-tetramethyl-[1,1':4',1":4",1"'-quatrefoil]-4,4"'-dicarboxylic acid.

14. The method of claim 9, wherein the metal complex is:

15. The method of claim 9, wherein the catalyst complex comprises the following chemical structure:

16. A method for performing a [2+2] cycloaddition, the method comprising the steps of: (a) forming a mixture of a first compound and a second compound in an organic solvent comprising the heterogeneous catalyst of claim 1; wherein the first compound and the second compound each contain a carbon-carbon double bond capable of undergoing a [2+2] cycloaddition; as well as (b) exposing the mixture to visible light irradiation to photoexcite the heterogeneous catalyst, wherein energy transfer from the photoexcited heterogeneous catalyst initiates a [2+2] cycloaddition between the carbon-carbon double bonds of the first compound and the second compound.

17. The method of claim 16, wherein at least one of the first compound and the second compound comprises an electron-deficient olefin.

18. The method of claim 16, wherein at least one of the first compound and / or the second compound has the following chemical structure: wherein EWG is an electron withdrawing group; optionally, wherein the electron withdrawing group is selected from -C(O)OR; -C(O)R'; -C(O)NR1R2; or -CN; and wherein R, R', R1 and R2 are each independently selected from hydrogen, a halogen group, a C1-C5 alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group, a cycloalkynyl group, a hydroxyl group, an aryl group, a heteroaryl group, a benzyl group, an acyl group, an ester group, a carbonyl group, a carboxylic acid group, an amino group, an amide group and a nitro group.

19. The method of claim 16, wherein at least one of the first compound and / or the second compound has a chemical structure according to any one of formulas (I)-(IV): wherein A, B, C, D and E are each independently selected from hydrogen, a halogen group; a C2-C5 alkyl group; an alkenyl group; an alkynyl group; a cycloalkyl group; a cycloalkenyl group; a cycloalkynyl group; a hydroxyl group; an alkoxy group; an aryl group; a heteroaryl group; a benzyl group; an acyl group; an ester group; a carbonyl group; a carboxylic acid group; an amino group; an amide group; and a nitro group; optionally wherein A and B; B and C; C and E; and E and D may be combined to form a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group; wherein Rx and Ry are each independently selected from hydrogen or alkyl; wherein Ra, Ra', Ra", Rb, Rb' and Rb" are each independently selected from hydrogen, hydrogen, halogen groups; C2-C5 alkyl; alkenyl; alkynyl; cycloalkyl; cycloalkenyl; cycloalkynyl; hydroxyl; alkoxy, aryl; heteroaryl; benzyl; acyl; ester; carbonyl; carboxylic acid; amino; amide; and nitro; wherein Q, Q', X, X', Z and Z' are each independently selected from hydrogen and alkyl; optionally, wherein Q and Z and Q' and Z' may be combined to form a cycloalkyl or heterocycloalkyl; in, Optionally, the carbon of the aromatic ring of formula (I), (III), (IV) or (V) is substituted with nitrogen.

20. The method of claim 16, wherein the visible light illumination comprises blue light; optionally wherein the blue light comprises a wavelength of 440 nm.

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