A method for preparing alkyl-substituted glycine derivatives driven by visible light

Abstract

The application belongs to the field of organic synthesis chemistry and relates to a method for preparing alkyl-substituted glycine derivatives by using a visible light-driven decarboxylation alkylation reaction. The method comprises the following steps: mixing glycine derivatives, N-hydroxyphthalimide (NHPI) ester, 2D-COF-4 and an organic solvent, reacting under a blue LED lamp for 24 hours in an argon environment, and obtaining alkyl-substituted glycine derivatives. The method avoids the use of noble metal photocatalysts, the heterogeneous photosensitizer in the reaction is easy to recycle and reuse, the scope of the substrate is wide, and the functional group compatibility is good; the method can be successfully applied to a kilogram-scale amplification experiment, has a good industrial application prospect, and uses a green solvent, ethanol, which is conducive to reducing production cost and production risk and meets the requirements of developing green and environment-friendly chemistry.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis chemistry, and in particular to a method for preparing alkyl-substituted glycine derivatives driven by visible light. Background Technology

[0002] Glycine is the most basic α-amino acid, and its direct derivatization and modification are of great significance for the synthesis of drugs containing non-natural amino acid fragments (a: Henninot, A.; Collins, JC; Nuss, JM, J. Med. Chem., 2018, 61, 1382-1414; b: Sharma, K.; Sharma, KK; Sharma, A.; Jain, R., Drug Discov. Today, 2023, 28, 103464). In the past few decades, chemists have shown increasing interest in the synthesis of functionalized glycine derivatives (Zhao, L.; Li, C.-J., Angew. Chem. Int. Ed., 2008, 47, 7075-7078). Among these, the use of visible light-driven α-C(sp...)... 3 The alkylation of H bonds to achieve the modification and synthesis of this type of compound has attracted much attention. This strategy can accurately and efficiently synthesize a variety of alkyl-substituted glycine derivatives in a green and sustainable manner (a: Hari Babu, M.; Sim, J., Eur. J. Org. Chem., 2022, 2022, e202200859; b: Wang, C.; Qi, R.; Wang, R.; Xu, Z., Acc. Chem. Res., 2023, 56, 2110-2125), which has good application value and prospects.

[0003] The synthesis methods reported so far based on this strategy can be divided into the following three types according to the type of photocatalyst used: (1) Homogeneous visible light driven C(sp) 3 Alkylation of C(sp) bonds, these methods mostly use transition metal complexes or organic dyes as photocatalysts to absorb visible light and initiate the reaction (a: Leng, L.; Ready, JM, ACS Catal., 2020, 10, 13196-13201; b: Xin, H.; Yuan, Z.-H.; Yang, M.; Wang, M.-H.; Duan, X.-H.; Guo, L.-N., GreenChem., 2021, 23, 9549-9553). (2) Visible light driven C(sp) without added photocatalyst 3(3) Visible light-driven C(sp) bond alkylation reactions, in which electron donor-acceptor (EDA) complexes can often be formed and act as photocatalysts (a: Fu, M.-C.; Shang, R.; Zhao, B.; Wang, B.; Fu, Y., Science, 2019, 363, 1429-1434; b: Crisenza, GEM; Mazzarella, D., Melchiorre, P., J. Am. Chem. Soc., 2020, 142, 5461-5476). 3 Asymmetric alkylation of C(sp)-H bonds: In these methods, asymmetric transition metal catalysis and visible light redox catalysis are perfectly integrated, achieving C(sp)-H bond asymmetric alkylation. 3 Stereoselective synthesis of alkylated glycine derivatives (a: Wang, C.; Guo, M.; Qi, R.; Shang, Q.; Liu, Q.; Wang, S.; Zhao, L.; Wang, R.; Xu, Z., Angew. Chem. Int. Ed., 2018, 57, 15841-15846; b: Che, C.; Li, Y.-N.; Cheng, X.; Lu, Y.-N.; Wang, C.-J., Angew. Chem. Int. Ed., 2021, 60, 4698-4704). The above schemes have achieved significant progress in reaction efficiency, selectivity, and applicable substrate range. However, from the perspective of green and sustainable chemistry, there is room for further improvement in terms of catalyst reusability, reaction flexibility, and the simplicity of post-reaction procedures.

[0004] In conclusion, the study of efficient and precise synthesis of alkyl-substituted glycine derivatives using readily available raw materials is of great significance. Summary of the Invention

[0005] In view of this, the present invention discloses a visible light-driven method for preparing alkyl-substituted glycine derivatives. This method uses a two-dimensional covalent organic framework with visible light response as a heterogeneous photocatalyst, and realizes a heterogeneous visible light-driven decarboxylation alkylation reaction with inexpensive and readily available raw materials. It achieves efficient and highly selective synthesis of alkyl-substituted glycine derivatives under mild reaction conditions.

[0006] The technical solution provided by this invention is specifically a method for preparing alkyl-substituted glycine derivatives under visible light driving. Using glycine derivatives of formula (I) and N-hydroxyphthalimide (NHPI) ester of formula (II) as starting materials, covalent organic framework material 2D-COF-4 is added. An organic solvent is used as the solvent, and the reaction is carried out under a blue LED light for 24 hours to synthesize the alkyl-substituted glycine derivative of formula (III). The reaction formula is as follows:

[0007]

[0008] Among them, R 1 It is an alkoxy or amino group; R 2 Ar is an alkyl group; Ar is an aryl group.

[0009] The structure of the covalent organic framework material 2D-COF-4 is as follows:

[0010]

[0011] Preferably, the R 1 Alkoxy groups include ethoxy, tert-butoxy, and benzyloxy; amino groups include benzylamino, etc.; the R 2 The alkyl group is cyclohexyl, cyclopentyl, cyclobutyl, etc. The Ar aryl group is phenyl, 4-methylphenyl, 4-isopropylphenyl, 4-methoxyphenyl, etc.

[0012] Preferably, the molar ratio of the glycine derivative to N-hydroxyphthalimide (NHPI) ester is 1:1.2.

[0013] Preferably, the dosage of 2D-COF-4 is 4 mg.

[0014] Preferably, the reaction temperature is room temperature.

[0015] Preferably, the reaction takes place in argon gas.

[0016] Preferably, the organic solvent is ethanol or dimethyl sulfoxide.

[0017] Preferably, the light source consists of two blue LED lamps, each with a power of 40W and a peak wavelength of 456nm.

[0018] This invention provides a method for synthesizing alkyl-substituted glycine derivatives. This method avoids the use of precious metal photocatalysts, the heterogeneous photosensitizer in the reaction is easy to recover and reuse, the substrate has a wide range of applicability and good functional group compatibility, this method can be successfully applied to gram-scale experiments and has good industrial application prospects, this method uses green solvent ethanol, which helps to reduce production costs and production risks, and meets the requirements for developing green and environmentally friendly chemistry.

[0019] It should be understood that the above general description and the following detailed description are exemplary and explanatory only, and do not limit the disclosure of the present invention. Detailed Implementation

[0020] The embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Rather, they are merely examples of systems consistent with some aspects of the invention as detailed in the appended claims.

[0021] Example 1:

[0022]

[0023] At room temperature, N-phenylglycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (20 mg of dark red solid, 77% yield).

[0024] At room temperature, N-phenylglycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (21 mg dark red solid, 80% yield).

[0025] 1 H NMR (500MHz, CDCl3) δ7.16 (dd, J=7.2, 8.6Hz, 2H), 6.72 (t, J=7.3Hz, 1H), 6.63 (d, J=7.6 Hz,2H),4.19-4.14(m,3H),3.87(d,J=6.1Hz,1H),1.88-1.67(m,6H),1.32-1.12(m,8H); 13C NMR (126MHz, CDCl3) δ173.56,147.34,129.14,117.94,113.38,61.90,60.68,41.19,29.49,29.07,26.07,25.98,25.94,14.18.HR-MS(ESI)[M+H] + m / z calcd forC 16 H 24 NO2 262.1807, found 262.1803.

[0026] Example 2:

[0027]

[0028] At room temperature, N-(4-isopropylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (20 mg of yellow liquid, 66% yield).

[0029] At room temperature, N-(4-isopropylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (21 mg yellow liquid, 69% yield).

[0030] 1 H NMR (500MHz, CDCl3) δ7.03(d,J=8.4Hz,2H),6.57(d,J=8.5Hz,2H),4.16(q,J=7.1Hz,2H),3.82(d,J=6.1H z,1H),2.82-2.76(m,1H),1.86-1.65(m,7H),1.26-1.23(m,5H),1.19(d,J=6.9Hz,6H),1.17-1.13(m,2H); 13C NMR (126MHz, CDCl3) δ173.81,145.35,138.44,127.01,113.41,62.20,60.63,41 .25,33.03,29.53,29.04,26.09,26.00,25.96,24.08,14.19.HR-MS(ESI)[M+H] + m / z calcd for C 19 H 30 NO2 304.2277, found 304.2270.

[0031] Example 3:

[0032]

[0033] At room temperature, N-(4-phenoxyphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (22 mg yellow solid, 62% yield).

[0034] At room temperature, N-(4-phenoxyphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (27 mg yellow solid, 76% yield).

[0035] 1 H NMR (500MHz, CDCl3) δ7.24 (dd, J=1.7, 6.9Hz, 2H), 6.98 (t, J=7.4Hz, 1H), 6.90-6.85 (m, 4H), 6.60 (d ,J=8.8Hz,2H),4.16(q,J=7.2Hz,2H),3.79(d,J=6.1Hz,1H),1.78-1.65(m,6H),1.25-1.13(m,8H); 13C NMR (126MHz, CDCl3) δ173.65,158.79,148.15,143.94,129.36,121.89,120.99,117.10,1 14.60,62.67,60.71,41.19,29.55,29.07,26.07,25.98,25.95,14.21.HR-MS(ESI)[M+H] + m / z calcd for C 22 H 28 NO3 354.2069, found354.2064.

[0036] Example 4:

[0037]

[0038] At room temperature, N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (5 mg of yellow solid, 13% yield).

[0039] At room temperature, N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborane-2-yl)phenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (16 mg yellow solid, 41% yield).

[0040] 1H NMR (500MHz, CDCl3) δ7.61(d,J=8.3Hz,2H),6.59(d,J=8.3Hz,2H),4.16(q,J=6.3Hz,2H),3.92(d,J=6.1Hz,1H),1.84-1.65(m,6H),1.33-1.13(m,20H); 13 C NMR (126MHz, CDCl3) δ173.16,149.79,136.24,112.28,83.11,61.14,60.79,41 .16,29.38,29.03,26.03,25.95,25.89,24.72,24.70,14.19.HR-MS(ESI)[M+H] + m / z calcd forC 22 H 35 BNO4 388.2659, found 388.2659.

[0041] Example 5:

[0042]

[0043] At room temperature, N-(4-methylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (19 mg yellow liquid, 69% yield).

[0044] At room temperature, N-(4-methylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain a yellow liquid (20 mg, yield 73%).

[0045] 1H NMR (500MHz, CDCl3) δ6.97(d,J=8.0Hz,2H),6.55(d,J=8.4Hz,2H),4.16(q,J=7.1 Hz,2H),3.82(d,J=6.2Hz,1H),2.23(s,3H),1.87-1.65(m,6H),1.28-1.12(m,8H); 13 CNMR (126MHz, CDCl3) δ173.74,145.04,129.63,127.21,113.62,62.33,60.6 1,41.18,29.50,29.08,26.09,25.99,25.95,20.26,14.19.HR-MS(ESI)[M+H] + m / z calcd forC 17 H 26 NO2 276.1964, found 276.1958.

[0046] Example 6:

[0047]

[0048] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (25 mg dark red liquid, 86% yield).

[0049] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (25 mg dark red liquid, 86% yield).

[0050] 1H NMR (500MHz, CDCl3) δ6.75(d,J=8.9Hz,2H),6.60(d,J=8.9Hz,2H),4.15(q,J=7.2 Hz,2H),3.76(d,J=6.2Hz,1H),3.73(s,3H),1.88-1.66(m,6H),1.29-1.13(m,8H); 13 CNMR(126MHz,CDCl3)δ173.88,152.50,141.48,115.09,114.70,63.27,60.5 9,55.60,41.17,29.55,29.10,26.09,25.99,25.96,14.19.HR-MS(ESI)[M+H] + m / z calcd forC 17 H 26 NO3 292.1913, found 292.1909.

[0051] Example 7:

[0052]

[0053] At room temperature, N-(4-fluorophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (18 mg yellow solid, 64% yield).

[0054] At room temperature, N-(4-fluorophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (19 mg yellow solid, 68% yield).

[0055] 1H NMR (500MHz, CDCl3) δ6.86 (t, J=8.7Hz, 2H), 6.56 (dd, J=4.4, 9.0Hz, 2H), 4.16 (q,J=7.1Hz,2H),3.77(d,J=6.2Hz,1H),1.87-1.66(m,6H),1.28-1.13(m,8H); 13 C NMR (126MHz, CDCl3) δ173.56,157.00,155.12,143.73,143.71,115.63,115.45, 114.54,114.48,62.84,60.69,41.12,29.51,29.05,26.04,25.94,25.91,14.16. 19 F NMR(376MHz, CDCl3)δ-127.05.HR-MS(ESI)[M+H] + m / z calcd for C 16 H 23 FNO2 280.1713, found 280.1708.

[0056] Example 8:

[0057]

[0058] At room temperature, N-(4-chlorophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (16 mg dark red solid, 54% yield).

[0059] At room temperature, N-(4-chlorophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, and filtered. The solvent was removed by concentration under reduced pressure. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (17 mg dark red solid, 58% yield).

[0060] 1 H NMR (500MHz, CDCl3) δ7.10(d,J=8.8Hz,2H),6.54(d,J=8.8Hz,2H),4.17(q,J=7.1Hz,2H),3.80(d,J=6.1Hz,1H),1.84-1.65(m,6H),1.28-1.12(m,8H); 13 C NMR (126MHz, CDCl3) δ173.27,145.91,128.97,122.56,114.51,62.05,60.83,41.09,29.46,29.03,26.02,25.93,25.89,14.19.HR-MS(ESI)[M+H] + m / z calcd for C 16 H 23 ClNO2296.1417, found 296.1414.

[0061] Example 9:

[0062]

[0063] At room temperature, N-(4-bromophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (24 mg dark red solid, 71% yield).

[0064] At room temperature, N-(4-bromophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (30 mg dark red solid, 88% yield).

[0065] 1H NMR (500MHz, CDCl3) δ7.23(d,J=8.7Hz,2H),6.50(d,J=8.8Hz,2H),4.17(q,J=7.1Hz,2H),3.80(d,J=6.1Hz,1H),1.84-1.65(m,6H),1.27-1.12(m,8H); 13 C NMR (126MHz, CDCl3) δ173.20,146.33,131.85,114.98,109.60,61.92,60.85,41.08,29.45,29.03,26.01,25.93,25.89,14.19.HR-MS(ESI)[M+H] + m / z calcd for C 16 H 23 BrNO2340.0912, found 340.0908.

[0066] Example 10:

[0067]

[0068] At room temperature, N-(4-iodophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (24 mg yellow solid, 62% yield).

[0069] At room temperature, N-(4-iodophenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, and filtered. The solvent was removed by concentration under reduced pressure. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (28 mg yellow solid, 72% yield).

[0070] 1H NMR (500MHz, CDCl3) δ7.40(d,J=8.7Hz,2H),6.40(d,J=8.7Hz,2H),4.17(q,J=7.2Hz,2H),3.80(d,J=6.1Hz,1H),1.83-1.65(m,6H),1.28-1.12(m,8H); 13 C NMR (126MHz, CDCl3) δ173.15,146.95,137.73,115.56,61.69,60.85,41.09,29.45,29.02,26.02,25.93,25.89,14.20.HR-MS(ESI)[M+H] + m / z calcd for C 16 H 23 INO2 388.0774, found388.0769.

[0071] Example 11:

[0072]

[0073] At room temperature, N-(3,4-dimethylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, filtered, and the filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (23 mg dark red liquid, 80% yield).

[0074] At room temperature, N-(3,4-dimethylphenyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (24 mg dark red liquid, 83% yield).

[0075] 1H NMR (500MHz, CDCl3) δ6.92(d,J=8.0Hz,1H),6.48(d,J=2.5Hz,1H),6.40(dd,J=2.6,8.1Hz,1H),4.19-4.14( m,2H),3.97(s,1H),3.83(d,J=6.1Hz,1H),2.19(s,3H),2.14(s,3H),1.87-1.67(m,6H),1.29-1.14(m,8H); 13 C NMR (126MHz, CDCl3) δ173.81,145.47,137.18,130.14,125.96,115.37,110.73,62.21,6 0.55,41.21,29.51,29.05,26.09,25.98,25.95,19.88,18.55,14.20.HR-MS(ESI)[M+H] + m / z calcd for C 18 H 28 NO2290.2120, found 290.2115.

[0076] Example 12:

[0077]

[0078] At room temperature, N-(2-naphthyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (21 mg dark red solid, 67% yield).

[0079] At room temperature, N-(2-naphthyl)glycine ethyl ester (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (24 mg dark red solid, 77% yield).

[0080] 1 H NMR (500MHz, CDCl3) δ7.68-7.58(m,3H),7.36(t,J=7.6Hz,1H),7.20(t,J=7.5Hz,1H),6.93(dd,J=2.4,8.8Hz ,1H),6.82(d,J=2.4Hz,1H),4.22-4.15(m,2H),4.01(d,J=6.2Hz,1H),1.93-1.68(m,6H),1.31-1.17(m,8H); 13 C NMR (126MHz, CDCl3) δ173.50,144.97,134.88,128.93,127.70,127.47,126.20,125.89,122.15,1 18.13,105.33,61.86,60.77,41.15,29.52,29.20,26.09,26.00,25.95,14.22.HR-MS(ESI)[M+H] + m / z calcd forC 20 H 26 NO2 312.1964, found 312.1959.

[0081] Example 13:

[0082]

[0083] At room temperature, N-phenylglycine phenyl methyl ester (0.1 mmol), cyclohexyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (14 mg yellow solid, 43% yield).

[0084] At room temperature, N-phenylglycine phenyl methyl ester (0.1 mmol), cyclohexyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (18 mg yellow solid, 56% yield).

[0085] 1 H NMR (500MHz, CDCl3) δ7.35-7.32(m,3H),7.29-7.27(m,2H),7.16(dd,J=7.3,8.6Hz,2H),6.73(t,J=7.3Hz,1H),6. 63(d,J=7.4Hz,2H),5.14(s,2H),3.93(d,J=6.1Hz,1H),1.85-1.73(m,5H),1.68-1.65(m,2H),1.24-1.15(m,4H); 13 C NMR (126MHz, CDCl3) δ173.51,147.26,135.47,129.18,128.41,128.18,118.10,1 13.46,66.52,61.98,41.20,29.51,29.02,26.02,25.92,25.89.HR-MS(ESI)[M+H] + m / z calcd for C 21 H 26 NO2 324.1964, found 324.1958.

[0086] Example 14:

[0087]

[0088] At room temperature, 0.1 mmol of 2-(phenylamino)-1-(1-pyrrolyl)acetone, 0.12 mmol of cyclohexylNHPI ester, 4 mg of 2D-COF-4, and 2.0 mL of ethanol were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (21 mg white solid, 73% yield).

[0089] At room temperature, 0.1 mmol of 2-(phenylamino)-1-(1-pyrrolyl)acetone, 0.12 mmol of cyclohexylNHPI ester, 4 mg of 2D-COF-4, and 2.0 mL of dimethyl sulfoxide were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LEDs with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (20 mg white solid, 70% yield).

[0090] 1 H NMR (500MHz, CDCl3) δ7.15-7.11(m,2H),6.67(t,J=7.3Hz,1H),6.62(d,J=7.9Hz,2H),4.46(d,J=9.3Hz,1H),3.97-3.94(m, 1H),3.54(t,J=6.8Hz,2H),3.50-3.42(m,2H),1.97-1.93(m,3H),1.86-1.82(m,2H),1.78-1.65(m,6H),1.21-1.09(m,4H); 13 C NMR (126MHz, CDCl3) δ171.55,148.20,129.11,117.43,113.52,60.51,46.51 ,45.64,41.91,30.05,28.84,26.14,26.04,25.97,23.96.HR-MS(ESI)[M+H] + m / z calcd for C 18 H 27 N2O2 87.2123, found 287.2119.

[0091] Example 15:

[0092]

[0093] At room temperature, 2-phenylamino-N-benzylmethylacetamide (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by concentration under reduced pressure. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under reduced pressure to give the corresponding alkyl-substituted glycine derivative (19 mg white solid, 59% yield).

[0094] At room temperature, 2-phenylamino-N-benzylmethylacetamide (0.1 mmol), cyclohexylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (21 mg white solid, 65% yield).

[0095] 1 H NMR (500MHz, CDCl3) δ7.25-7.14(m,6H),7.06(t,J=7.5Hz,1H),6.78(t,J=7.3Hz,1H),6.60(d,J=7.9Hz,2H),4.49(dd,J=6.2,14.9 Hz,1H),4.37(dd,J=5.7,14.9Hz,1H),3.93(s,1H),3.62(t,J=4.1Hz,1H),2.07-2.02(m,1H),1.80-1.68(m,5H),1.32-1.13(m,5H); 13 CNMR (126MHz, CDCl3) δ172.54,147.19,138.05,129.24,128.43,127.48,127.21,118. 87,113.59,64.76,43.06,41.01,30.20,28.10,26.12,26.08,25.98.HR-MS(ESI)[M+H] + m / z calcd for C 21 H 27N2O 323.2123, found 323.2119.

[0096] Example 16:

[0097]

[0098] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclopentylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (21 mg dark red liquid, 76% yield).

[0099] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclopentylNHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (21 mg dark red liquid, 76% yield).

[0100] 1 H NMR (500MHz, CDCl3) δ6.75 (d, J = 8.9 Hz, 2H), 6.61 (d, J = 8.9 Hz, 2H), 4.14 (q, J = 7.1 Hz, 2H), 3.77 (d, J = 8. 0Hz,1H),3.73(s,3H),2.23-2.18(m,1H),1.85-1.82(m,1H),1.72-1.43(m,7H),1.22(t,J=7.1Hz,3H); 13 C NMR (126MHz, CDCl3) δ174.33,152.52,141.32,114.98,114.67,62.02,60.58,55.57,43.06,29.33,28.93,25.21,25.00,14.16.HR-MS(ESI)[M+H] + m / z calcd for C 16 H 24NO3 278.1756, found 278.1751.

[0101] Example 17:

[0102]

[0103] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclobutyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (19 mg dark red liquid, 72% yield).

[0104] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), cyclobutyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (17 mg dark red liquid, 65% yield).

[0105] 1 H NMR(500MHz, CDCl3) δ6.76(d,J=8.9Hz,2H),6.60(d,J=8.9Hz,2H),4.18-4.11(m,2H),3.88 (d,J=8.2Hz,1H),3.73(s,3H),2.67-2.62(m,1H),2.09-1.83(m,6H),1.22(t,J=7.1Hz,3H); 13 C NMR (126MHz, CDCl3) δ173.56,152.58,141.27,114.99,114.68,62.23,60.65,55.58,38.24,25.43,24.65,17.96,14.21.HR-MS(ESI)[M+H] + m / z calcd forC 15 H 22NO3 264.1600, found 264.1594.

[0106] Example 18:

[0107]

[0108] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), 1-adamantyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (26 mg yellow solid, 76% yield).

[0109] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), 1-adamantyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) (30 mg yellow solid, 87% yield).

[0110] 1 H NMR (500MHz, CDCl3) δ6.75(d,J=8.9Hz,2H),6.63(d,J=8.9Hz,2H),4.13(q,J=7.1Hz,2 H),3.73(s,3H),3.54(s,1H),2.02(s,3H),1.83-1.56(m,12H),1.23(t,J=7.1Hz,3H); 13 C NMR (126MHz, CDCl3) δ173.03,152.52,141.82,115.40,114.65,67.86,60.29,55.58,38.92,36.76,36.01,28.26,14.23.HR-MS(ESI)[M+H] + m / z calcd forC 21 H 30 NO3 344.2226, found344.2220.

[0111] Example 19:

[0112]

[0113] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), tert-butyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (23 mg dark red liquid, 87% yield).

[0114] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), tert-butyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (20 mg dark red liquid, 75% yield).

[0115] 1 H NMR (500MHz, CDCl3) δ6.76 (d, J = 8.9 Hz, 2H), 6.64 (d, J = 8.9 Hz, 2H), 4.15-4.10 (m, 2H), 3.73 (s, 3H), 3.66 (s, 1H), 1.22 (t, J = 7.1Hz, 3H), 1.06 (s, 9H); 13 C NMR(126MHz, CDCl3)δ173.53,152.66,141.61,115.51,114.67,66.95,60.39,55.60,34.18,26.68,14.19.HR-MS(ESI)[M+H] + m / z calcd for C 15 H 24 NO3 266.1756, found 266.1752.

[0116] Example 20:

[0117]

[0118] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), phenoxymethyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and ethanol (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under an argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction was complete, the solvent was removed by vacuum concentration. 1 mL of toluene was added to the residue, and the mixture was filtered. The filtrate was concentrated under vacuum to give the corresponding alkyl-substituted glycine derivative (21 mg dark red liquid, 67% yield).

[0119] At room temperature, N-(4-methoxyphenyl)glycine ethyl ester (0.1 mmol), phenoxymethyl NHPI ester (0.12 mmol), 2D-COF-4 (4 mg), and dimethyl sulfoxide (2.0 mL) were added sequentially to a 10 mL reaction tube. The mixture was stirred for 24 hours under argon atmosphere and irradiated by two 40 W blue LED lamps with a peak wavelength of 456 nm. After the reaction, the mixture was extracted with ethyl acetate (5 mL x 3), the organic layer was washed with saturated brine, dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to remove the solvent. The corresponding alkyl-substituted glycine derivatives were purified by column chromatography (silica gel column) to obtain (21 mg dark red liquid, 67% yield).

[0120] 1 H NMR (500MHz, CDCl3) δ7.29-7.25(m,2H),6.97(t,J=7.4Hz,1H),6.90(d,J=7.7Hz,2H),6.78(d,J=8.9Hz,2H),6.66(d ,J=8.9Hz,2H),4.37-4.34(m,2H),4.30(t,J=7.5Hz,1H),4.21(q,J=7.1Hz,2H),3.74(s,3H),1.23(t,J=7.2Hz,3H); 13 C NMR(126MHz, CDCl3)δ171.49,158.21,152.86,140.29,129.37,121.27,115.36,114.75,114.59,68.28,61.40,57.58,55.55,14.08.HR-MS(ESI)[M+H] + m / z calcd for C 18 H 22 NO4 316.1549, found 316.1543.

[0121] The preferred embodiments of the present invention disclosed above are merely illustrative of the invention. These preferred embodiments do not exhaustively describe all details, nor do they limit the invention to the specific implementations described. Clearly, many modifications and variations can be made based on the content of this specification. This specification selects and specifically describes these embodiments to better explain the principles and practical applications of the invention, thereby enabling those skilled in the art to better understand and utilize the invention. The invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for preparing alkyl-substituted glycine derivatives under visible light-driven conditions, characterized in that, include: Using glycine derivatives of formula (I) and N-hydroxyphthalimide (NHPI) esters of formula (II) as starting materials, covalent organic framework material 2D-COF-4 was added, and the reaction was carried out under a blue LED lamp for 24 hours in an organic solvent to synthesize alkyl-substituted glycine derivatives of formula (III). The reaction formula is as follows: Among them, R 1 It is an alkoxy or amino group; R 2 Ar is an alkyl group; Ar is a phenyl group. The organic solvent is ethanol or dimethyl sulfoxide; The two blue LED lights have a power of 40 W and a peak wavelength of 456 nm. The structure of the covalent organic framework material 2D-COF-4 is as follows: 。 2. The method according to claim 1, characterized in that: The R mentioned 1 The alkoxy group is ethoxy, tert-butoxy, or benzyloxy; the amino group is benzylamino; the R group is... 2 The alkyl group is cyclohexyl, cyclopentyl, or cyclobutyl.

3. The method according to claim 1, characterized in that: The molar ratio of the glycine derivative to N-hydroxyphthalimide (NHPI) ester is 1:1.

2.

4. The method according to claim 1, characterized in that: The dosage of 2D-COF-4 is 4 mg.

5. The method according to claim 1, characterized in that: The reaction temperature was room temperature.

6. The method according to claim 1, characterized in that: The reaction takes place in argon gas.

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