A method for iron-catalyzed dehydrogenative coupling of benzylic c-h bonds with quinones

Abstract

The application discloses a method for dehydrogenation coupling of a benzyl C-H bond and a quinone compound catalyzed by iron, and the method comprises the following steps: in a solvent, taking the quinone compound as a substrate, a peroxide as an oxidant, iron as a catalyst, and an amino acid and a derivative thereof as a ligand, catalyzing the dehydrogenation coupling reaction of the benzyl C(sp 3 )‑H bond and the quinone compound to generate a benzylated quinone compound. The method has the advantages of wide source, low cost and environmental protection of the catalyst, wide source and low cost of the oxidant, mild reaction condition, high selectivity, use of 1-2 equivalents of an alkylated substrate, good functional group compatibility of the substrate and wide application range of the substrate, and realization of the functional group functionalization reaction of the benzyl C(sp 3 )‑H bond. Under the optimized reaction condition, the yield of the target product can reach 97% after separation.

Description

Technical Field

[0001] This invention belongs to the fields of catalytic synthesis technology and fine chemical synthesis, specifically relating to a method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds. Background Technology

[0002] Quinones are an important class of organic compounds with wide applications in chemistry, materials science, medicine, and biology. Methyl-substituted quinones exhibit good biological activity; for example, vitamins K1 and K3 have excellent blood-clotting properties; coenzyme Q... 10 Capable of driving ATP production, leucone exhibits significant anticancer effects. Allyl-substituted quinones are also a crucial class of bioactive substances and important components of cell membranes, playing a vital role in cell metabolism and photosynthesis. Benzyl-substituted quinones are important intermediates in the synthesis of bioactive substances and also have significant applications in medicine. Therefore, introducing methyl, allyl, and benzyl groups into quinone compounds will greatly enhance their potential in biological and pharmaceutical applications.

[0003] Several challenges remain in current benzylation of quinones, such as limited substrate applicability, the need for strong oxidants (Y. Dong, J. Yang, W. Ji-Yu et al, RSCAdv., 2019, 9, 27588–27592), expensive and uneconomical substrates (M. Donzel, M. Elhabiri, E. Davioud-Charvet, J. Org. Chem. 2021, 86, 10055-10066), large excess of alkylbenzene, use of noble metal catalysis (JD. Garloway, DN. Mai, and R.D. Baxter, J. Org. Chem. 2019, 84, 12131-12137), and limited expansion to complex molecules. These factors severely limit the large-scale application of this method. Summary of the Invention

[0004] Objective of the Invention: To address the problems existing in the prior art, this invention provides a method for iron-catalyzed dehydrogenation coupling of benzylic C-CH bonds with quinone compounds. This invention is a method for iron-catalyzed oxidation of benzylic C(sp) bonds with a suitable oxidant. 3This invention discloses a method for the dehydrogenation coupling of quinone compounds with α-H bonds. This method not only provides an economical and applicable new approach for the synthesis of benzylated quinone compounds, but also solves a series of problems existing in current benzylated quinone reactions, such as demanding reaction conditions, low reaction yields, and the need for precious metal catalysts. The method of this invention requires only one step, does not require acid-base interaction, uses a small amount of alkylating substrate, and features widely available, inexpensive, and environmentally friendly catalysts; inexpensive and low-toxicity oxidants; widely available and stable substrates; mild reaction conditions and good selectivity; good compatibility of substrate functional groups and a wide range of substrate applications; mild reaction conditions, good selectivity, and high yield; compatibility with drug molecules and drug derivatives; and excellent ability to achieve benzylated quinone reactions.

[0005] Technical Solution: To achieve the above objectives, the present invention provides a method for iron-catalyzed dehydrogenation coupling of benzylic C-CH bonds with quinone compounds, comprising the following steps: in a solvent, using quinone compounds as substrates, alkylbenzenes as alkylation substrates, peroxides as oxidants, iron as catalysts, and amino acids or their derivatives as ligands, catalyzing the dehydrogenation coupling of benzylic C(sp) bonds. 3 The -H bond dehydrogenates and couples with quinone compounds to form benzylated quinone compounds;

[0006] The general formula for the reaction is as follows:

[0007]

[0008] In the formula: R1 represents hydrogen, alkyl or aromatic ring; R2 represents hydrogen, halogen, methoxy or ester group; R3 represents alkyl, tert-butyl, methoxy, carbonyl, ester group, thiophene, naphthone, cyano, nitro, halogen or heterocyclic ring; R4 represents alkyl, benzoyl, hydroxyl, isopropyl, halogen or aromatic ring.

[0009] Wherein, R1 represents a substituent on the aryl group in a quinone aromatic hydrocarbon, wherein R1 represents hydrogen, C1-C4 alkyl or aryl; R2 is a substituent on the double bond of a quinone, wherein R2 represents hydrogen, halogen, methoxy or ester group.

[0010] Wherein, R3 represents a substituent on the aromatic (hetero) ring of the benzene ring, wherein R3 represents hydrogen, C1-C4 alkyl, tert-butyl, methoxy, carbonyl, ester, thiophene, naphthone, cyano, nitro, halogen or heterocyclic ring; R4 represents a substituent at the benzyl position, wherein R4 represents hydrogen, C1-C4 alkyl, benzoyl, hydroxyl, isopropyl, halogen or aromatic ring.

[0011] The iron is selected from any one or more of the following: ferrous acetate, ferrous sulfate, ferrous ammonium sulfate, ferric sulfate, ferrous oxalate, ferric oxalate, ferrous fluoride, ferric fluoride, ferrous bromide, ferric bromide, ferrous iodide, ferric iodide, ferric chloride, ferric perchlorate (III) hydrate, 1,1'-bis(diphenylphosphine)ferrocene, ferrous phthalocyanine, ferric nitrate, ferric oxide, ferric tetroxide, ferrous trifluoromethanesulfonate, ferric trifluoromethanesulfonate, ferrous chloride, ferrous acetylacetone, ferric acetylacetone, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferric 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferrous 1,3-diphenylpropanedione, ferric 1,3-diphenylpropanedione, ferric benzoylacetone, ferrous ferricyanide, and ferric ferricyanide.

[0012] The ligand is selected from any one or more of the following: L-serine, D-cysteine, aspartic acid, D-arginine, isoserine, L-threonine, L-tyrosine, BOC-L-proline, BOC-glycine-glycine-glycine, 2-allyl-N-FMOC-L-glycine, BOC-D-phenylalanine, L-cysteine, D-serine, β-thiovaline, D-proline, D-valine, L-proline, L-phenylalanine, N-BOC-N'-triphenylmethyl-L-histidine, L-tryptophan, N-BOC-L-leucine, L-histidine, BOC-L-glutamic acid, L-cysteine, L-homocysteine, S-acetamidomethyl-N-tert-butoxycarbonyl-L-cysteine, N-acetyl-L-cysteine, and N,N'-bis(tert-butoxycarbonyl)-L-cysteine.

[0013] The oxidant is selected from any one or more of potassium persulfate, ammonium persulfate, sodium persulfate, tert-butyl hydroperoxide, hydrogen peroxide, peracetic acid, m-chloroperoxybenzoic acid, benzoyl peroxide, benzoyl tert-butyl peroxide, di-tert-butyl peroxide, potassium persulfate, dicumyl peroxide, 2-butanone peroxide, or bis(trimethylsilyl) peroxide.

[0014] Wherein, the solvent is an organic solvent, water, or an aqueous solution of an organic solvent, wherein the organic solvent is selected from methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propanediol, glycerol, n-butanol, isobutanol, tert-butanol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butanol, tert-amyl alcohol, 4-methyl-2-pentanol, isoamyl alcohol, 2-pentanol, 3-pentanol, cyclopentanol, n-pentanol, polyethylene glycol 200-10000, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dicarboxamide, N,N-diacetamide, ethyl acetate, 1,4-dioxane, or tetrahydrofuran; when the solvent is an aqueous solution of an organic solvent, the volume ratio of the organic solvent to water is 1:(0.1-5).

[0015] The molar ratio of the quinone compound, alkylbenzene, peroxide, amino acid or its derivative, and iron catalyst is 1:(1-2):(2-50):(0.002-20):(0.001-10).

[0016] Preferably, the molar ratio of the quinone compound, alkylbenzene, peroxide, amino acid or its derivative, and iron catalyst is 1:(1-2):(2-10):(0.004-0.8):(0.04-0.2).

[0017] The reaction is carried out at a temperature of 25–100°C for 1–24 hours.

[0018] The method of this invention utilizes iron as a catalyst, which is characterized by its high natural abundance, low cost, and low toxicity. Specific amino acid ligands are used to coordinate with the iron catalyst, forming a highly active catalytic species. This catalytic species, in conjunction with the oxidant and solvent, enables the alkylating reagent to form alkyl radicals that attack quinone reagents, exhibiting high activity and selectivity. Furthermore, the method of this invention uses mild reagents and a mild environment, solving the problem of harsh reaction conditions; it also solves the problem of benzylated quinones; the reaction directly attacks quinone reagents without pre-functionalization; iron is used as the catalyst, eliminating the need for precious metals, and the effect is significant. The method of this invention has the advantages of widely available, inexpensive, and environmentally friendly catalysts; widely available and inexpensive oxidants; mild reaction conditions and high selectivity; good compatibility of substrate functional groups and a wide range of substrate applications; compatibility with drug molecules and drug derivatives, and excellent ability to achieve benzylated quinone reactions. Under optimized reaction conditions, the yield of the target product after separation can reach 97%.

[0019] This invention first oxidizes low-valent iron to high-valent iron using an oxidant, generating corresponding anionic radicals. These anionic radicals abstract hydrogen ions from p-methyl anisole, providing alkyl radicals. Alkyl radicals are then generated through C / C bond cleavage. These alkyl radicals undergo radical addition with the alkene bond of naphthoquinone, generating benzyl-attached quinone radicals. Finally, the high-valent iron gains electrons and reverts to low-valent iron, and the benzyl-attached quinone is deprotonated to yield benzylated quinones, thus completing the catalytic cycle. Practical application has demonstrated excellent results. This is the first time that an amino acid ligand-promoted iron-catalyzed method has been applied to the coupling of alkylbenzenes and quinones. Unlike existing synthetic routes for benzylated quinones, which typically involve hydrogen transfer radical processes, this method utilizes the single-electron transfer between alkylbenzene and the iron catalyst to form an aryl radical cationic intermediate. Further deprotonation yields a benzyl radical, which then couples with the quinone, exhibiting excellent selectivity and activity towards quinones. This provides a new method and mechanism for the synthesis of this type of compound. By introducing amino acids or their derivatives to coordinate with iron catalysts, the activity and selectivity of iron catalysis are improved, thereby solving a series of problems existing in the quinone benzylation reaction, such as harsh reaction conditions, low reaction efficiency, the need for a large excess of alkylbenzene substrates, and the need to use noble metal catalysts.

[0020] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0021] (1) This invention provides an iron-catalyzed benzyl C(sp) ligand-promoted ligand-based catalytic process for amino acids and their derivatives. 3 This method involves the dehydrogenation coupling of quinones via the -H bond. It requires only one step, requires no acid or base, and offers unique advantages such as inexpensive, widely available, and environmentally friendly catalysts, ligands, and oxidants. The reaction conditions are mild and highly selective. The substrates are widely available, stable, and easy to handle. The substrate functional groups are compatible, and the substrates have a broad applicability. Experimental results demonstrate the suitability of this method for benzylating quinones, while existing technologies lack effective methods for forming highly active catalyst species.

[0022] (2) The method for benzylation of quinones provided by this invention is simple, easy and safe. It can directly obtain benzylated quinone compounds with distal functional groups in one step. Under optimized reaction conditions, the yield of the target product after separation can reach 97%. Moreover, the amount of alkylbenzene can be controlled at 1-2 equivalents, which can better reduce the reaction cost. It is a general, efficient, economical and environmentally friendly method for benzylating quinones.

[0023] (3) The reason why the method of the present invention can use ideal iron as a catalyst is that it uses amino acid ligands to coordinate with iron catalysts to form highly active catalytic species, so that the reaction can be carried out under very mild conditions for benzylation and quinoneization, and in particular, it can also achieve ideal catalytic effects on drug molecules and their derivatives.

[0024] (4) The benzylquinone compounds synthesized by the method of the present invention can be used as drugs or bioactive molecules, and are also important organic intermediates, which are widely used in the synthesis of pharmaceutical intermediates and high value-added fine chemicals. Detailed Implementation

[0025] The present invention can be better understood from the following embodiments. However, those skilled in the art will readily understand that the descriptions in the embodiments are for illustrative purposes only and should not, and will not, limit the invention as detailed in the claims.

[0026] Unless otherwise specified, the experimental methods described in the embodiments are conventional methods; unless otherwise specified, the reagents and materials can be obtained commercially or through simple preparation using existing technologies.

[0027] The specific structures of the substrates and products in the embodiments are shown in Table 1.

[0028] The reaction substrates 1b-1g and 2a-2x used in this invention are all reported compounds. Products for which NMR / mass spectrometry data are not provided in this invention are all known compounds.

[0029] Example 1

[0030] Synthesis of Compound 1

[0031] In a 25 mL reaction flask, ferric bromide (0.05 mmol), D-serine (0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2a (0.5 mmol), ethanol (2.0 mL), and potassium persulfate (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:0.5) yielded product 1 in 49% yield.

[0032] Example 2

[0033] Synthesis of Compound 2

[0034] In a 25 mL reaction flask, ferric chloride (0.1 mmol), L-homocysteine ​​(0.2 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2b (1 mmol), methanol (2.0 mL), and dicumyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was refluxed at 80 °C for 1 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:1) yielded product 2 in 74% yield.

[0035] Example 3

[0036] Synthesis of Compound 3

[0037] In a 25 mL reaction flask, ferrous trifluoromethanesulfonate (0.02 mmol), aspartic acid (0.8 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2c (1 mmol), tert-butanol (2.0 mL), and di-tert-butyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:2) yielded product 3 in 95% yield.

[0038] Example 4

[0039] Synthesis of Compound 4

[0040] In a 25 mL reaction flask, ferrous chloride (0.025 mmol), S-acetaminomethyl-N-tert-butoxycarbonyl-L-cysteine ​​(1.0 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2d (1 mmol), isopropanol (1.5 mL), water (2.5 mL), and hydrogen peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 12 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:4) to give product 4 in 97% yield.

[0041] Example 5

[0042] Synthesis of Compound 5

[0043] In a 25 mL reaction flask, ferrous acetylacetone (0.02 mmol), BOC-L-glutamic acid (0.04 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2e (1 mmol), glycerol (1.5 mL), water (0.5 mL), and peracetic acid (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, the mixture was separated by column chromatography (petroleum ether: ethyl acetate V / V = 10:2) to give product 5 in 84% yield.

[0044] 1 H NMR (400MHz, CDCl3): δ8.10-8.06(m,1H),8.05-8.01(m,1H),7.99(d,J=8.2Hz,2H) ,7.75-7.69(m,2H),7.32(d,J=8.2Hz,2H),6.61(s,1H),3.94(s,2H),3.90(s,3H). 13 CNMR (100MHz, CDCl3): δ184.18,184.06,157.52,150.18,134.39,132.70,132.64,131 .13,131.03,129.4,127.5,125.6,125.0,113.2,54.2,33.9ppm; HRMS(ESI)calcd.for C 19 H 14 O4H + [M+H] + m / z 307.0965 found m / z 307.0968; IR(KBr,cm -1 ):ν max 3305,3069,2922,2860,1673,1603,1498,1402,1324,1297,1262,1228,1097,939,887,765,660,582,451.

[0045] Example 6

[0046] Synthesis of Compound 6

[0047] In a 25 mL reaction flask, 0.08 mmol of acetylacetone iron, 0.16 mmol of L-tyrosine, 0.5 mmol of 1,4-naphthoquinone, 1 mmol of substrate 2f, 2.0 mL of n-butanol, and 5 mmol of tert-butyl hydroperoxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 85 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:3) yielded product 6 in 72% yield.

[0048] 1 H NMR (400MHz, CDCl3): δ8.06-8.00(m,2H),7.73-7.67(m,2H),7.32-7.27(m,4H),7.24-7.18(m,1H ),6.84(s,1H),4.32(t,J=7.6Hz,1H),3.72-3.61(m,2H),2.08-1.94(m,2H),1.63-1.50(m,2H).; 13 C NMR (100MHz, CDCl3): δ185.4,184.6,153.6),140.8,134.0,133.7,132.2,131.8,1 28.8,128.2,127.1,126.8,126.0,62.3,43.1,30.6,30.2ppm; HRMS(ESI)calcd.for C 20 H 18 O3H + [M+H] + m / z 307.1329found m / z 307.1325; IR(KBr,cm -1 ):ν max 3403,3026,2927,2861,1654,1602,1588,1495,1450,1271,1050,914,727,698,673,570,459.

[0049] Example 7

[0050] Synthesis of Compound 7

[0051] In a 25 mL reaction flask under normal nitrogen pressure, ferric trifluoromethanesulfonate (0.05 mmol), L-cysteine ​​(0.1 mmol), 1,4-naphthoquinone (0.5 mmol), 2 g of substrate (1 mmol), acetonitrile (2.0 mL), and m-chloroperoxybenzoic acid (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 100 °C for 24 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:3) yielded product 7 in 68% yield.

[0052] 1 H NMR (400MHz, CDCl3): δ8.07-8.00(m,2H),7.71-7.65(m,2H),7.35-7.23(m,4H),7.19(dt,J=9.2,4.2Hz,1H),6 .98(d,J=0.6Hz,1H),3.98(d,J=11.2Hz,1H),2.53-2.29(m,1H),1.00(d,J=6.5Hz,3H),0.85(d,J=6.5Hz,3H); 13 C NMR (100MHz, CDCl3): δ199.3,183.9,148.9,141.1,134.9,134.7,132.9,132.8,13 1.0,128.6,127.6,126.1,125.7,125.2,34.8,30.8,7.2ppm.HRMS(ESI)calcd.for C 20 H 16 O3H + [M+H + ]m / z 305.1172, found305.1176; IR(KBr,cm -1 ):ν max 3308,2947,2851,1681,1592,1361,1297,1248,1221,1011,949,772,564cm -1 .

[0053] Example 8

[0054] Synthesis of Compound 8

[0055] In a 25 mL reaction flask, ferrous fluoride (0.1 mmol), N,N'-bis(tert-butyloxycarbonyl)-L-cysteine ​​(0.4 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2h (1 mmol), acetonitrile (1.5 mL), water (1.5 mL), and potassium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 5 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, column chromatography (petroleum ether:ethyl acetate V / V = 10:3) was performed to give product 8 in 69% yield.

[0056] 1H NMR (400MHz, CDCl3): δ8.10-8.07(m,1H),8.05-8.02(m,1H),7.97-7.93(m,2H ),7.74-7.69(m,2H),7.57(t,J=7.4Hz,1H),7.46(t,J=7.6Hz,2H),7.37(d,J=7 .2Hz,2H),7.31(t,J=7.4Hz,2H),7.23(t,J=7.2Hz,1H),6.80(d,J=0.8Hz,1H), 5.10-5.05(m,1H),3.80(dd,J=17.8,8.4Hz,1H),3.66(dd,J=17.8,6.4Hz,1H). 13 C NMR (100MHz, CDCl3): δ196.7,185.2,184.2,152.7,140.4,136.4,133.8,133.7,133.4,132.3, 131.8,128.9,128.7,128.1,128.0,127.3126.9,126.0,43.0,39.5.ppm.HRMS(ESI)calcd.forC 17 H 10 Cl2O2H + [M+H] + m / z 367.1329, found m / z367.1329; IR(KBr,cm -1 ):ν max 3028,2921,2849,1660,1596,1580,1444,1275,1203,982,747,690,545.

[0057] Example 9

[0058] Synthesis of Compound 9

[0059] In a 25 mL reaction flask, ferrous iodide (0.08 mmol), N-acetyl-L-cysteine ​​(0.32 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2i (1 mmol), trifluoroethanol (2.0 mL), and benzoyl peroxide (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 2 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:5) yielded product 9 in 63% yield.

[0060] 1H NMR (400MHz, CDCl3): δ8.12-8.09(m,1H),8.07-8.02(m,1H),7.76-7.71(m,2H),7.28(t ,J=2.0Hz,1H),7.26(s,1H),7.17(t,J=8.1Hz,1H),6.58(d,J=1.2Hz,1H),3.88(s,2H), 13 C NMR (100MHz, CDCl3): δ184.18,184.06,157.52,150.18,134.39,132.70,132.64,131 .13,131.03,129.4,127.5,125.6,125.0,113.2,54.2,33.9ppm; HRMS(ESI)calcd.for C 18 H 16 FO3H + [M+H] + m / z 344.9921found m / z 344.9928; IR(KBr,cm -1 ):ν max 3305,3069,2922,2860,1673,1603,1498,1402,1324,1297,1262,1228,1097,939,887,765,660,582,451.

[0061] Example 10

[0062] Synthesis of Compound 10

[0063] In a 25 mL reaction flask under normal nitrogen pressure, ferrous sulfate (0.05 mmol), L-cysteine ​​(0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2j (0.5 mmol), dimethyl sulfoxide (1.5 mL), water (0.5 mL), and sodium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 8 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: diethyl ether V / V = 10:2) to give product 10 in 66% yield.

[0064] Example 11

[0065] Synthesis of Compound 11

[0066] In a 25 mL reaction flask under normal nitrogen pressure, ferric iodide (0.05 mmol), aspartic acid (0.1 mmol), naphthoquinone (0.5 mmol), substrate 2K (1 mmol), 1,3-propanediol (4.0 mL), and potassium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 24 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: diethyl ether V / V = 10:1) to give product 11, with a yield of 49%.

[0067] 1 H NMR (400MHz, CDCl3): δ7.60(d,J=7.6Hz,1H),7.36(t,J=6.8Hz,1H),7.25(t,J=7.5Hz,2H),6.96(dt,J=15.6,7.0Hz,1H),5.82(dt,J=15.6,1 .5Hz,1H),3.72(s,3H),2.88(t,J=7.3Hz,2H),2.48(s,3H),2.24-2.19(m,2H),1.75-1.68(m,2H),1.54-1.47(m,2H),1.42-1.35ppm(m,2H); 13 C NMR (100MHz, CDCl3): δ204.5,167.1,149.4,138.1,137.8,131.9,131.1,128.2, 125.6,121.0,51.4,41.4,32.0,28.7,27.8,24.1,21.2ppm; HRMS(ESI)calcd.for C 17 H 22 O3H + [M+H + ]m / z275.1642, found 275.1633; IR(KBr,cm -1 ):ν max 3359,3190,2924,2853,1723,1684,1602,1435,1270,1198,1039,980,857,735.

[0068] Example 12

[0069] Synthesis of Compound 12

[0070] In a 25 mL reaction flask, ferrous fluoride (0.02 mmol), BOC-glycine-glycine-glycine (0.2 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2L (1 mmol), dichloromethane (2.0 mL), and 2-butanone peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 95 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:3) yielded product 12 in 69% yield.

[0071] 1 HNMR (400MHz, CDCl3): δ8.17-8.12(m,1H),8.06-8.02(m,1H),7.77-7.70(m,2H),7. 21-7.17(m,2H),7.14-7.08(m,1H),6.37(s,1H),4.08(d,J=1.4Hz,2H),2.44(s,3H). 13 CNMR (100MHz, CDCl3): δ185.1184.9,149.5,139.3136.6,135.3,133.8,133.7,132.1 ,132.0,129.8,129.2,127.6127.3,126.7126.1,36.624.0ppm.HRMS(ESI)calcd.for C 18 H 13 BrO2H + [M+H] + m / z 341.0172foundm / z341.0173; IR(KBr,cm -1 ):ν max 3287,3046,2919,1664,1590,1454,1407,1295,1023,962,758,700,607,539.

[0072] Example 13

[0073] Synthesis of Compound 13

[0074] In a 25 mL reaction flask, ferrous ferricyanide (0.001 mmol), L-serine (0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2m (1 mmol), dimethyl sulfoxide (2.0 mL), and dicumyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether: diethyl ether V / V = 10:7) yielded product 13 in 67% yield.

[0075] 1 HNMR (400MHz, CDCl3): 1 H NMR (400MHz, CDCl3): δ8.19-8.16(m,1H),8.06-8.03(m,1H),7.77-7.73(m,3H),7.19(d,J=7 .5Hz,1H),6.91(t,J=7.8Hz,1H),6.15(t,J=1.9Hz,1H),4.15(d,J=1.8Hz,2H),2.28(s,3H). 13 C NMR (100MHz, CDCl3): δ184.9,184.8,148.5,138.5,137.8,137.7,134.3,133.9,133.7, 132.2,132.1,130.7,129.1,126.7,126.2,103.1,38.0,21.3ppm.HRMS(ESI)calcd.for C 18 H 13 IO2H + [M+H] + m / z 389.0033, foundm / z389.0033; IR(KBr,cm -1 ):ν max 3048,2910,1660,1590,1450,1328,1297,1250,1108,937,774,661,564.

[0076] Example 14

[0077] Synthesis of Compound 14

[0078] In a 25 mL reaction flask, ferric ferricyanide (0.05 mmol), BOC-L-proline (0.002 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2n (1 mmol), acetonitrile (1.0 mL), water (1.0 mL), and ammonium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 20:1) to give product 14 in 91% yield.

[0079] 1H NMR (400MHz, CDCl3): δ8.15-8.11(m,1H),8.08-8.04(m,1H),7.78-7.73(m,3H),7.67-7.62 (m,1H),7.55-7.49(m,3H),7.47-7.42(m,1H),7.42-7.36(m,2H),6.71(s,1H),3.97(s,2H). 13 C NMR (100MHz, CDCl3): δ185.1185.0,150.4,145.0,136.9,135.8,133.9,133.8,132.9,132.1,132. 1,130.1,130.0,129.8,129.3,127.6,126.8126.2,118.7,111.2,35.6.ppm.HRMS(ESI)calcd.for C 28 H 17 NO2H + [M+H] + m / z 400.1332found m / z 400.1331; IR(KBr,cm -1 ):ν max 3057,2923,2226,1664,1596,1477,1442,1289,1161,1112,1007,949,826,768,566.

[0080] Example 15

[0081] Synthesis of Compound 15

[0082] In a 25 mL reaction flask under normal nitrogen pressure, ferrous phthalocyanine (0.02 mmol), L-histidine (0.15 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 2O (1 mmol), 1,2-dichloroethane (2.0 mL), and benzoyl tert-butyl peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 6 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 40:1) to give product 15 in 60% yield.

[0083] 1H NMR (400MHz, CDCl3): δ8.11-8.08(m,1H),8.07-8.04(m,1H),7.77-7.73(m, 2H),7.63(d,J=8.2Hz,2H),7.39(d,J=8.0Hz,2H),6.66(s,1H),3.95(s,2H). 13 C NMR (100MHz, CDCl3): δ184.7,184.6,149.2,142.5,136.1,134.0,133.9,132.6, 132.0,131.9,130.1,126.8,126.3,118.6,111.1,36.0ppm.HRMS(ESI)calcd.for C 18 H 11 NO2H + [M+H] + m / z274.0863found m / z 274.0870; IR(KBr,cm -1 ):ν max 3065,2919,2847,2224,1660,1608,1501,1359,1291,935,824,753,708,564.

[0084] Example 16

[0085] Synthesis of Compound 16

[0086] In a 25 mL reaction flask, ferrous trifluoromethanesulfonate (0.05 mmol), BOC-D-phenylalanine (0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1p (1 mmol), ethyl acetate (2.0 mL), and potassium persulfate (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 90 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:7) yielded product 16 in 76% yield.

[0087] Example 17

[0088] Synthesis of Compound 17

[0089] In a 25 mL reaction flask, 0.04 mmol of 1,3-diphenylpropanedione, 0.04 mmol of L-cysteine, 0.5 mmol of 1,4-naphthoquinone, 1 mmol of substrate 1q, 2.0 mL of N,N-diacetamide, and 1.5 mmol of hydrogen peroxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 90 °C for 6 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 17 in 54% yield.

[0090] Example 18

[0091] Synthesis of Compound 18

[0092] In a 25 mL reaction flask, ferrous oxalate (0.1 mmol), BOC-L-proline (0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1r (0.5 mmol), 1,4-dioxane (2.0 mL), and hydrogen peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 10 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:3) yielded product 18 in 73% yield.

[0093] Example 19

[0094] Synthesis of Compound 19

[0095] In a 25 mL reaction flask, ferrous sulfate (0.05 mmol), D-valine (0.15 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1s (1 mmol), toluene (2.0 mL), and sodium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:dichloromethane V / V = 10:5) yielded product 19 in 68% yield.

[0096] 1 H NMR (400MHz, CDCl3): δ8.16-8.12(m,1H),8.04-8.00(m,1H),7.91(s,1H),7.77-7.71(m,2H),7.32(d,J=7.8Hz,1H),7.00(d, J=7.8Hz,1H),6.27(s,1H),4.67(t,J=4.6Hz,1H),2.62-2.57(m,2H),2.54-2.46(m,1H),2.38(s,3H),2.30-2.22ppm(m,1H). 13CNMR (100MHz, CDCl3): δ197.4,184.5,184.3,152.6,140.0,137.8,137.0,135.2,134.0,133.8,1 32.8,132.1,131.8,129.0,127.6,126.8,126.2,37.9,34.9,27.6,21.0ppm; HRMS(ESI)calcd.for C 21 H 16 O3H + [M+H] + m / z317.1172, found m / z 317.1168; IR(KBr,cm -1 ):ν max 3308,3042,2921,1656,1592,1497,1407,1271,1130,914,673,550,457.

[0097] Example 20

[0098] Synthesis of Compound 20

[0099] In a 25 mL reaction flask, ferrous 1,3-diphenylpropanedione (0.08 mmol), BOC-L-glutamic acid (0.4 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1t (1 mmol), tetrahydrofuran (1.0 mL), water (1.0 mL), and m-chloroperoxybenzoic acid (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 100 °C for 2 h. Upon completion of the reaction, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, and after solvent removal under reduced pressure, column chromatography (petroleum ether:ethyl acetate V / V = 20:3) was performed to obtain product 20 in 65% yield.

[0100] 1 H NMR (400MHz, CDCl3): δ8.17-8.13(m,1H),8.10(d,J=8.8Hz,1H),8.06-8.02(m,1H),7.80-7.73(m,2H),6.92(dd,J=8.8,2 .4Hz,1H),6.55(d,J=2.4Hz,1H),6.29(s,1H),4.66(t,J=4.2Hz,1H),3.81(s,3H),2.58-2.45(m,3H),2.29-2.21(m,1H). 13C NMR (100MHz, CDCl3): δ195.8,184.5,184.3,164.1,152.2,145.2,137.0,134.1,133.9,132.1,13 1.9,130.1,126.9,126.8,126.2,114.1,113.3,55.5,38.5,34.5,27.6ppm.HRMS(ESI)calcd.forC 21 H 17 O4H + [M+H] + m / z 333.1122found m / z 311.1118; IR(KBr,cm -1 ):ν max 3308,3055,2935,2844,1656,1588,1454,1413,1291,1244,1153,1027,819,727,558.

[0101] Example 21

[0102] Synthesis of Compound 21

[0103] In a 25 mL reaction flask, ferrous chloride (0.05 mmol), BOC-D-phenylalanine (0.03 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1u (1 mmol), sec-butanol (2.0 mL), and potassium persulfate (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 50 °C for 24 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 21 in 93% yield.

[0104] 1 H NMR (400MHz, CDCl3): δ8.21-8.16(m,1H),8.07-8.02(m,1H),7.76(t,J=5.2Hz,2H),7.70(dd,J=13.8,8.3Hz,2H),7.51(t,J=7.4Hz,2H), 7.31(d,J=6.8Hz,1H),7.23(d,J=6.8Hz,1H),6.53(s,1H),5.21-5.13(m,1H),4.02(dd,J=17.4,9.0Hz,1H),3.26(dd,J=17.4,2.9Hz,1H). 13C NMR (100MHz, CDCl3): δ185.4,185.3,154.1,144.2,142.7,138.9,134.1,133.9,133.8,132.2,132.0, 131.7,128.3,127.9,126.7,126.1,123.8,122.9,120.6,119.7,42.7,39.7ppm.HRMS(ESI)calcd.for C 22 H 14 O2H + [M+H] + m / z 311.1067foundm / z 311.1062; IR(KBr,cm -1 ):ν max 3310,3034,2919,2849,1930,1643,1588,1497,1353,1283,1242,1139,974,906,788,725,669,461.

[0105] Example 22

[0106] Synthesis of Compound 22

[0107] In a 25 mL reaction flask, ferrous ammonium sulfate (0.1 mmol), N,N'-bis(tert-butyloxycarbonyl)-L-cysteine ​​(0.4 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1v (1 mmol), ethylene glycol (2.0 mL), and di-tert-butyl peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 3 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 10:1) yielded product 22 in 51% yield.

[0108] 1H NMR (400MHz, CDCl3): δ8.33-8.29(m,1H),8.23(d,J=8.0Hz,1H),8.11-8.07(m,1H),8.06-8.02(m,1 H),7.82-7.77(m,1H),7.75-7.70(m,2H),7.27(d,J=6.4Hz,2H),7.11(d,J=1.6Hz,1H),6.97(d,J=4. 8Hz,1H),6.76(s,1H),4.44(t,J=7.4Hz,1H),2.81-2.75(m,1H),2.26-2.18(m,1H),2.01(d,J=5.4Hz ,1H),1.90(d,J=6.0Hz,2H),1.72-1.67(m,1H),1.42(s,1H),1.34-1.24(m,13H),0.93-0.80(m,6H). 13 C NMR (100MHz, CDCl3): δ185.5,184.6,153.8,141.9,134.0,133.7,132.2,131.9,127.3, 126.8,125.9,125.9,121.7,38.8,34.4,31.6,27.5,22.4,14.0.;HRMS(ESI)calcd.for C 20 H 20 SO2H + [M+H] + m / z 325.1257, found m / z325.1257; IR(KBr,cm -1 ):ν max 3094,2925,2855,1666,1590,1454,1308,1252,776,634.

[0109] Example 23

[0110] Synthesis of Compound 23

[0111] In a 25 mL reaction flask, ferric perchlorate(III) hydrate (0.05 mmol), L-tryptophan (0.5 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1w (2 mmol), glycerol (2.0 mL), and 2-butanone peroxide (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 100 °C for 2 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 23 in 60% yield.

[0112] 1H NMR (400MHz, CDCl3): δ8.07-8.02(m,2H),7.71-7.67(m,2H),7.22(dd,J=21.6,8.2Hz,4H),6.95(s,1H),3.95(d,J=1 1.2Hz, 1H), 3.66 (d, J = 7.2Hz, 1H), 3.63 (s, 3H), 1.44 (d, J = 7.2Hz, 3H), 0.99 (d, J = 6.4Hz, 3H), 0.85 (d, J = 6.4Hz, 3H). 13 C NMR (100MHz, CDCl3): δ185.5,184.6,175.0,174.9,153.2,140.1,138.9,133.9,133.7,132.2,131.7,128.7 ,127.7,126.8,125.9,58.4,52.0,50.9,44.9,31.1,21.5,21.4,18.5,18.5,18.4ppm.HRMS(ESI)calcd.for C 24 H 24 O4H + [M+H] + m / z 377.1747found m / z 377.1745; IR(KBr,cm -1 ):ν max 3318,2952,2869,1732,1658,1598,1452,1442,1308,1215,1161,1067,968,782,708,585

[0113] Example 24

[0114] Synthesis of Compound 24

[0115] In a 25 mL reaction flask, ferric oxide (0.2 mmol), L-homocysteine ​​(0.1 mmol), 1,4-naphthoquinone (0.5 mmol), substrate 1x (2 mmol), cyclopentanol (2.0 mL), and 2-butanone peroxide (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 9 h. At the end of the reaction, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The combined organic phases were washed with water (5 mL × 3), and the organic phase was collected. After removing the solvent under reduced pressure, the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:4) to give product 24 in 91% yield.

[0116] 1H NMR (400MHz, CDCl3): δ8.10-8.07(m,1H),8.05-8.02(m,1H),7.97-7.93(m,2H ),7.74-7.69(m,2H),7.57(t,J=7.4Hz,1H),7.46(t,J=7.7Hz,2H),7.37(d,J=7 .2Hz,2H),7.31(t,J=7.4Hz,2H),7.23(t,J=7.2Hz,1H),6.80(d,J=0.8Hz,1H), 5.10-5.05(m,1H),3.80(dd,J=17.8,8.4Hz,1H),3.66(dd,J=17.8,6.4Hz,1H). 13 C NMR (100MHz, CDCl3) δ205.4,185.2,184.3,152.7,149.1,133.8,133.8,133.7,132.4,132.2,13 1.8,126.9,126.0,119.7,111.6,111.3,55.9,55.9,47.8,38.9,30.2ppm.HRMS(ESI)calcd.forC 22 H 20 O5H + [M+H] + m / z 365.1380; IR (KBr, cm -1 ):ν max 3386,2917,2846,1711,1666,1507,1421,1328,1258,1147,1030,758,465.

[0117] Example 25

[0118] Synthesis of Compound 25

[0119] In a 25 mL reaction flask, benzoyl acetone iron (0.05 mmol), N-BOC-L-leucine (0.1 mmol), 2-chloro-naphthoquinone 1b (0.5 mmol), p-methylbenzonitrile (1 mmol), tert-amyl alcohol (1.5 mL), water (0.5 mL), and hydrogen peroxide (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 3 h. At the end of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with diethyl ether (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:3) to give product 25 in 83% yield.

[0120] 1H NMR (400MHz, CDCl3): δ8.18-8.15(m,1H),8.13-8.10(m,1H),7.79-7.75(m,2H),7.58(d,J=8.3Hz,2H),7.48(d,J=8.3Hz,2H),4.22(s,2H). 13 C NMR (100MHz, CDCl3): δ182.2,177.5,145.0,144.4,142.2,134.5,134.3,132.4, 131.4,131.2,130.0,127.4,127.2,118.7,110.9,34.0ppm.HRMS(ESI)calcd.for C18H10ClNO2H+[M+H]+m / z308.0473found m / z 308.0474; IR(KBr,cm-1):νmax 3059,2919,2849,2220,1670,1590,1477,1279,1100,937,714,613,469; Mp:120.8-121.3℃.

[0121] Example 26

[0122] Synthesis of Compound 26

[0123] In a 25 mL reaction flask, ferric oxalate (0.05 mmol), 2-allyl-N-FMOC-L-glycine (0.08 mmol), 2-methoxy-naphthoquinone 1c (0.5 mmol), methyl p-methylbenzoate (1 mmol), tert-amyl alcohol (2.0 mL), and bis(trimethylsilyl)peroxide (1 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 40 °C for 2 h. Upon completion of the reaction, direct chromatography (petroleum ether:diethyl ether V / V = 10:3) yielded product 26 in 60% yield.

[0124] 1 H NMR (400MHz, CDCl3): δ8.08-8.03(m,2H),7.94-7.91(m,2H),7.72-7.68(m,2H),7.39(d,J=8.4Hz,2H),4.14(s,3H),3.98(s,2H),3.88(s,3H). 13C NMR (100MHz, CDCl3) δ184.9,181.6,167.0,144.6,134.0,133.4,132.6,131.7,131 .4,129.8,129.0,128.2,126.3,126.2,61.3,52.0,29.7ppm.HRMS(ESI)calcd.for C 20 H 16 O5H+[M+H]+m / z337.1071found m / z 337.1072; IR(KBr,cm-1):νmax 3087,2939,1673,1595,1454,1341,1297,1062,957,792,747,713,695,459; Mp:125.2-125.8℃.

[0125] Example 27

[0126] Synthesis of Compound 27

[0127] In a 25 mL reaction flask, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl ionone (0.05 mmol), D-serine (0.1 mmol), 1,4-anthraquinone 1d (0.5 mmol), 2-cyano-4'-methylbiphenyl (1 mmol), isobutanol (1.5 mL), water (0.5 mL), and ammonium persulfate (2 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 70 °C for 6 h. At the end of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether: dichloromethane V / V = 10:5) to give product 27 in 65% yield.

[0128] 1 H NMR (400MHz, CDCl3): δ8.67(s,1H),8.60(s,1H),8.09-8.03(m,2H),7.76(d,J=7.8Hz,1H),7 .71-7.62(m,4H),7.53(dd,J=14.6,8.0Hz,4H),7.46-7.40(m,4H),6.81(s,1H),4.03(s,2H). 13C NMR (100MHz, CDCl3): δ185.1,184.9,168.4,150.5,138.4,137.7,135.7,133.8,133.7,1 32.1,132.1,129.5,126.7,126.1,125.3,120.6,118.4,35.7,24.6.HRMS(ESI)calcd.for C 28 H 17 NO2H+[M+H]+m / z400.1332found m / z 400.1331; IR(KBr,cm-1):νmax 3351,2919,2849,2218,1668,1615,1454,1194,1019,753,471; Mp:184.2–184.8℃.

[0129] Example 28

[0130] Synthesis of Compound 28

[0131] In a 25 mL reaction flask, ferrous iodide (0.05 mmol), D-arginine (0.1 mmol), 5-methoxy-naphthoquinone 1e (0.5 mmol), 2-cyano-4'-methylbiphenyl (1 mmol), benzonitrile (2 mL), and di-tert-butyl peroxide (3 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 80 °C for 24 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 20:1) yielded product 28, with a yield of 61%.

[0132] 1 H NMR (400MHz, CDCl3): δ8.67(s,1H),8.60(s,1H),8.09-8.03(m,2H),7.76(d,J=7.8Hz,1H),7 .71-7.62(m,4H),7.53(dd,J=14.6,8.0Hz,4H),7.46-7.40(m,4H),6.81(s,1H),4.03(s,2H). 13 C NMR (100MHz, CDCl3): δ185.1,184.9,168.4,150.5,138.4,137.7,135.7,133.8,133.7,1 32.1,132.1,129.5,126.7,126.1,125.3,120.6,118.4,35.7,24.6.HRMS(ESI)calcd.for C 28 H 17NO2H+[M+H]+m / z400.1332found m / z 400.1331; IR(KBr,cm-1):νmax 3446,2929,2847,2226,1654,1625,1588,1472,1439,1310,1227,1044,943,772,531; Mp:132.2–132.8℃.

[0133] Example 29

[0134] Synthesis of Compound 29

[0135] In a 25 mL reaction flask, 1,1'-bis(diphenylphosphine)ferrocene (0.02 mmol), L-cysteine ​​(0.1 mmol), 2-bromo-naphthoquinone 1f (0.5 mmol), 2-cyano-4'-methylbiphenyl (1 mmol), N,N-dicarboxamide (1.5 mL), water (0.5 mL), and sodium persulfate (1.5 mmol) were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 25 °C for 6 h. Upon completion of the reaction, ammonia (0.5 mL, 25%) was added, and the mixture was stirred for 1 h. Immediately afterwards, 5 mL of water was added, and the mixture was extracted with ethyl acetate (5 mL × 3). The organic phases were combined, the solvent was removed under reduced pressure, and the mixture was separated by column chromatography (petroleum ether:ethyl acetate V / V = 20:3) to give product 29 in 90% yield.

[0136] 1 H NMR (400MHz, CDCl3): δ7.26(s,1H),7.24(s,1H),7.21-7.15(m,3H),6.58(d,J=1.5Hz,1H),3.85(s,2H),2.10(s,3H),2.04(d,J=1.5Hz,3H). 13 CNMR (100MHz, CDCl3): δ188.3,187.2,145.4,142.7,141.8,138.0,133.1,128.6,128.5,126.4,31.7,15.9,12.7ppm.HRMS(ESI)calcd.for C 15 H 14 O2H+[M+H]+m / z227.1067found m / z 227.1070; IR(KBr,cm-1):νmax 3378,2929,2839,2208,1678,1620,1450,1190,1011,725,425; Mp:176.2–176.8℃.

[0137] Example 30

[0138] Synthesis of Compound 30

[0139] In a 25 mL reaction flask, 0.1 mmol of 2,2,6,6-tetramethyl-3,5-heptadecyl iron, 0.2 mmol of N-BOC-N'-triphenylmethyl-L-histidine, 0.5 mmol of 2-acetoxy-1,4-naphthoquinone, 1 mmol of p-bromotoluene, 2.0 mL of ethanol, and 1 mmol of di-tert-butyl peroxide were added sequentially. After thorough mixing at room temperature, the reaction mixture was reacted at 60 °C for 12 h. Upon completion of the reaction, direct chromatography (petroleum ether:ethyl acetate V / V = 40:7) yielded product 30 in 81% yield.

[0140] 1 H NMR (400MHz, CDCl3): δ8.10-8.05(m,2H),7.75-7.71(m,2H),7.38(d,J=8.4Hz,2H),7.17(d,J=8.4Hz,2H),3.86(s,2H),2.41(s,3H). 13 C NMR (100MHz, CDCl3): δ184.1,1781,167.8,151.5,136.9,136.1,134.2,134.0,131 .7,131.7,130.7,130.6,126.8,126.7,120.6,29.5,20.4ppm.HRMS(ESI)calcd.for C19H13BrO4H+[M+H]+m / z 385.0070found m / z385.0072; IR(KBr,cm -1 ):νmax3448,3057,1666,1590,1450,1343,1301,1248,1149,776,721,673,585,455; Mp:113.8-114.3℃.

[0141] The structural formulas of the raw materials and products in Examples 1-30 and the corresponding experimental results are shown in Table 1 below:

[0142]

[0143] Table 1

[0144]

[0145]

[0146]

[0147]

[0148] Example 31

[0149] Example 31 uses the same method as Example 4, except that the molar ratio of quinone reagent, alkylbenzene, sodium persulfate, amino acid derivative, and iron catalyst is 1:2:3:0.005:0.003.

[0150] Example 32

[0151] Example 32 uses the same method as Example 4, except that the molar ratio of quinone reagent, alkylbenzene, sodium persulfate, amino acid derivative, and iron catalyst is 1:1:50:20:15.

[0152] Example 33

[0153] Example 33 uses the same method as Example 4, except that the solvent is entirely water and the total volume remains unchanged.

[0154] Comparative Example 1

[0155] The method of Comparative Example 1 is the same as that of Example 4, except that no iron catalyst is added and the yield of the target product is 0.

[0156] Comparative Example 2

[0157] The method of Comparative Example 2 is the same as that of Example 4, except that no amino acid ligands are added, which greatly reduces the reaction yield to less than 20%.

[0158] Comparative Example 3

[0159] The method of Comparative Example 3 is the same as that of Example 4, except that no oxidant is added and the yield of the target product is 0.

[0160] Comparative Example 4

[0161] Comparative Example 4 followed the same method as Example 4, except that it used a non-amino acid ligand, 1,10-phenanthroline, resulting in a yield of only 6%. Furthermore, other phosphorus-containing ligands, such as triphenylphosphine, tris(pentafluorophenyl)phosphine, and bis(triphenylphosphine)ammonium chloride, also yielded poor results and very low yields.

[0162] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the invention. The various iron catalysts in this invention can theoretically coordinate with amino acid ligands to form highly active iron catalyst species, thereby facilitating the smooth progress of the reaction. Amino acid ligands are promoters for the benzylated quinone reaction, utilizing their ability to coordinate with iron. Theoretically, various amino acids and their derivatives all possess coordination functions and should achieve similar effects. Various peroxides are oxidizing agents. Alkylation involves the breaking of carbon-hydrogen bonds, while the various substituents on the aromatic ring affect the electron cloud density within the ring and the steric hindrance during the reaction. That is, the modification of substituents only affects the reaction to a certain extent and does not play a decisive role in the occurrence of the reaction. Anyone skilled in the art will readily understand that, without departing from the scope of the present invention, variations or modifications can be made to obtain corresponding embodiments. For example, the substituents can be replaced, changed, or modified within the scope of the present invention to achieve the method of the present invention. Any modifications, alterations, or equivalent changes made to the above embodiments based on the present invention without departing from the spirit of the present invention shall still fall within the scope of the present invention.

Claims

1. A method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds, characterized in that, The steps include: in a solvent, using quinone compounds as substrates, alkylbenzenes as alkylation substrates, peroxides as oxidants, iron as catalysts, and amino acids or their derivatives as ligands, catalyzing the benzylic C(sp) group. 3 The -H bond of a quinone compound undergoes dehydrogenation coupling to form a benzylated quinone compound; the general reaction formula is shown below: ; In the formula, R1 represents hydrogen or C1-C4 alkyl; R2 represents hydrogen or halogen; R3 represents hydrogen, C1-C4 alkyl, methoxy, or halogen; R4 represents hydrogen; The iron is selected from any one or more of the following: ferrous acetate, ferrous sulfate, ferrous ammonium sulfate, ferric sulfate, ferrous oxalate, ferric oxalate, ferrous fluoride, ferrous fluoride, ferrous bromide, ferrous bromide, ferrous iodide, ferric iodide, ferric chloride, ferric perchlorate (III) hydrate, 1,1'-bis(diphenylphosphine)ferrocene, ferrous phthalocyanine, ferric nitrate, iron oxide, iron tetroxide, ferrous trifluoromethanesulfonate, ferrous trifluoromethanesulfonate, ferrous chloride, ferrous acetylacetone, ferric acetylacetone, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferrous 2,2,6,6-tetramethyl-3,5-heptadecyl iron, ferrous 1,3-diphenylpropanedione, ferrous 1,3-diphenylpropanedione, ferric benzoylacetone, ferrous ferricyanide, and ferric ferricyanide. The ligand is selected from any one or more of the following: L-serine, D-cysteine, aspartic acid, D-arginine, isoserine, L-threonine, L-tyrosine, BOC-L-proline, BOC-glycine-glycine-glycine, 2-allyl-N-FMOC-L-glycine, BOC-D-phenylalanine, L-cysteine, D-serine, β-thiovaline, D-proline, D-valine, L-proline, L-phenylalanine, N-BOC-N'-triphenylmethyl-L-histidine, L-tryptophan, N-BOC-L-leucine, L-histidine, BOC-L-glutamic acid, L-cysteine, L-homocysteine, S-acetamidomethyl-N-tert-butoxycarbonyl-L-cysteine, N-acetyl-L-cysteine, and N,N'-bis(tert-butoxycarbonyl)-L-cysteine.

2. The method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds according to claim 1, characterized in that, The oxidant is selected from any one or more of potassium persulfate, ammonium persulfate, sodium persulfate, tert-butyl hydroperoxide, hydrogen peroxide, peracetic acid, m-chloroperoxybenzoic acid, benzoyl peroxide, benzoyl tert-butyl peroxide, di-tert-butyl peroxide, potassium persulfate, diisopropylbenzene peroxide, 2-butanone peroxide, or bis(trimethylsilyl)peroxide.

3. The method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds according to claim 1, characterized in that, The solvent is an organic solvent, water, or an aqueous solution of an organic solvent. The organic solvent is selected from methanol, ethanol, ethylene glycol, n-propanol, isopropanol, 1,3-propanediol, glycerol, n-butanol, isobutanol, tert-butanol, trifluoroethanol, 2-methyl-2-butanol, 3-methoxybutanol, sec-butanol, tert-amyl alcohol, 4-methyl-2-amyl alcohol, isoamyl alcohol, 2-amyl alcohol, 3-amyl alcohol, cycloamyl alcohol, n-amyl alcohol, acetonitrile, benzonitrile, toluene, acetone, dichloromethane, 1,2-dichloroethane, dimethyl sulfoxide, N,N-dicarboxamide, N,N-diacetamide, ethyl acetate, 1,4-dioxane, or tetrahydrofuran. When the solvent is an aqueous solution of an organic solvent, the volume ratio of the organic solvent to water is 1:(0.1-5).

4. The method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds according to claim 1, characterized in that, The molar ratio of the quinone compound, alkylbenzene, peroxide, amino acid or its derivative, and iron catalyst is 1:(1-2):(2-50):(0.002-20):(0.001-10).

5. The method for iron-catalyzed dehydrogenation coupling of benzylic CH bonds with quinone compounds according to claim 1, characterized in that, The molar ratio of the quinone compound, alkylbenzene, peroxide, amino acid or its derivative, and iron catalyst is 1:(1-2):(2-10):(0.004-0.8):(0.04-0.2).

6. The method for iron-catalyzed oxidation of benzylic CH bonds and dehydrogenation coupling with quinone compounds according to claim 1, characterized in that, The reaction is carried out at a temperature of 25–100°C for 1–24 hours.

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