Method for preparing triarylmethane through asymmetric photochemical reaction of pyridine triazole and boric acid catalyzed by chiral primary amine

Abstract

The invention discloses a method for preparing triarylmethane through asymmetric photochemical reaction of pyridine triazole and boric acid catalyzed by chiral primary amine, and belongs to the field of organic synthesis.An efficient modular asymmetric photochemical strategy is developed, the synthetic route is as follows: # imgabs0 #, the adopted chiral catalyst is one of C1-C9, and the structural formula of C1-C9 is as follows: # imgabs1 #; according to the present invention, pyridine triazole represented by a formula I and boric acid represented by a formula II are adopted as substrates, novel chiral diamine-derived pyrrole or primary amine is adopted as a catalyst, and a variety of triarylmethane with high yield and high enantioselectivity are successfully and efficiently synthesized; the method not only shows wide substrate applicability and excellent functional group tolerance, but also accurately synthesizes a series of deuterated derivatives by using low-cost DO as a deuterium source, and provides an efficient and economical path for synthesizing high-value molecules containing chiral C-D bonds.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing triarylmethane by asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by chiral primary amine. Background Art

[0002] The synthesis of enantiomerically enriched triarylmethanes has long been a core research topic in asymmetric catalysis, mainly due to their wide applications in medicinal chemistry, fluorescent probes, dyes, and nonlinear optical materials. To date, a variety of efficient methods have been developed for the asymmetric synthesis of electron-rich (nitrogen-containing) aromatic derivatives, such as indoles, pyrroles, and phenols. These strategies usually rely on the generation of electrophilic intermediates through (nitrogen-containing) aromatic derivatives or the direct addition of (nitrogen-containing) aromatics to diaryl-substituted carbocations. However, these methods perform poorly in the synthesis of electron-deficient nitrogen-containing aromatic derivatives such as pyridine (Zeniou, M.; Fève, M.; Mameri, S.; Dong, J.; Salomé, Chen, W.; EI-Habr, E.A.; Bousson, F.; Sy, M.; Obszynski, J.; Boh, A.; Villa, P.; Kahn, S.A.; Didier, B.; Bagnard, D.; Junier, M.-P.; Chneiweiss, H.; Haiech, J.; Hibert, M.; Kilhoffer, M.-C. Chemical library screening and structure-function relationship studies identify bisacodyl as a potent and selective cytotoxic agent towards quiescent human glioblastoma tumor stem-like cells. PLoS ONE 2015, 10, e0134793.). Notably, the literature on the synthesis of these biologically important compounds is limited and relies primarily on two basic asymmetric transition metal-catalyzed C–H bond functionalization strategies. The first strategy achieves the synthesis of diarylpyridylmethanes via symmetry breaking, i.e., the addition of a C(sp) 2 )–H bonds. For example, the Yu research group used a chiral complex constructed from Pd(OAc)2 and a secondary amino acid derived from L-leucine to promote the reaction with alkylboronic acids (Shi, B.-F.; Maugel, N.; Zhang, Y.-H.; Yu, J.-Q. Pd II-catalyzed enantioselectiveactivation of C(sp 2 )-H and C(sp 3 )-H bonds using monoprotected amino acids aschiral ligands.Angew.Chem.,Int.Ed.2008,47,4882-4886.). Subsequently, Li and his team used B2pin2 as a reaction partner to achieve the borylation reaction (Song,P.;Hu,L.;Yu,T.;Jiao,J.;He,Y.;Xu,L.;Li,P.Development of a tunable chiral pyridine ligand unit for enantioselectiveiridium-catalyzed CH borylation.ACS Catal.2021,11,7339-7349.). The second strategy is to asymmetrically synthesize the C(sp) of arylquinolyl methane by reaction with aryl bromide or aryl boronic acid. 3 )–H bonds for arylation, a method previously described by Glorius (Kim, JH; Greβies, S.; Boultadakis-Arapinis, M.; Daniliuc, C.; Glorius, F. Ru(I) / NHC*-catalyzed site- and enantioselective functionalization of C(sp 3 )-H bonds toward chiral triarylmethanes.ACSCatal.2016,6,7652-7656.) and You(Zhang,Z.-Y.;Gou,B.-B.;Wang,Q.;Gu,Q.;You,S.-L.Rh-catalyzed asymmetric C(sp 3 )-H arylation of 8-benzylquinolines with arylboronic acids. Adv. Synth. Catal. 2024, 366, 774-779.) research group reported. Although these methods are innovative, they have significant limitations in regulating the types of nitrogen-containing aromatics, mainly due to the inherent need for C–H bond activation. In addition, deuterated isotope labeling technology, which is crucial in drug discovery, still faces challenges in the above two methods.

[0003] This application proposes a new chiral pyrrole-primary amine catalyst, which successfully achieves the synthesis of a variety of triarylmethanes with high yield and excellent enantioselectivity. This method shows a remarkable breadth of substrate scope in regulating aromatic and nitrogen-containing aromatic substituents. In particular, it is worth mentioning that this method provides an efficient route for the synthesis of high-value molecules containing chiral C-D bonds, and uses low-cost D2O as a deuterium source, which has good application prospects. Summary of the invention

[0004] The object of the present invention is to provide a method for preparing triarylmethane by asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by chiral primary amine.

[0005] Based on the above purpose, the present invention adopts the following technical solutions:

[0006] A method for preparing triarylmethane by asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by chiral primary amine, the synthesis route is as follows: The chiral catalyst used is one of C1 to C9.

[0007] The structural formulas of C1 to C9 are as follows: The specific process is as follows:

[0008] Under a protective atmosphere, the pyridine triazole of formula I, the boric acid of formula II and the chiral catalyst are added to an organic solvent, and the reaction is completed by stirring at room temperature to -40°C under visible light irradiation, and the triarylmethane of formula III is obtained by separation and purification; wherein R is H, methyl, F, Cl, Br, CF3 or methoxy, and Ar is 1 for

[0009] Ar 2 for R 3 represents 1 to 3 identical or different substituents, and each R 3 independently selected from H, F, Cl, Br, C1-C4 saturated alkyl, cyclohexyl, methoxy, CF 3、 Ph, vinyl, ethynyl, Trimethylsilyl or triphenylsilyl, R 4 represents 1 to 3 identical or different substituents, and each R 4 Independently selected from F, Cl, Br, methyl, methoxy, CF3, phenyl, ethyl, vinyl, ethynyl or G=N or C.

[0010] Furthermore, the molar ratio of the pyridinetriazole shown in formula I to the boric acid shown in formula II is 1:(1-2), and the amount of the chiral catalyst added is 15-25% of the molar amount of the pyridinetriazole.

[0011] Furthermore, the base is one of K2CO3, KHCO3 and K3PO4 or a mixture of two of them in any proportion, and the added amount of the base is 1 to 3 times the molar amount of pyridinetriazole.

[0012] Furthermore, the organic solvent is one or a mixture of any proportion of two of PhCF3, PhF, PhBr and t-BuPh.

[0013] Furthermore, the maximum wavelength of the visible light is λ max =365nm, visible light is provided by 1 to 2 3W blue LED lamps.

[0014] Furthermore, the method further comprises adding D2O, wherein the amount of D2O added is 15 to 25 times the molar amount of pyridinetriazole.

[0015] The chiral triarylmethane prepared by the preparation method.

[0016] Specifically, the present application synthesized the following compounds:

[0017]

[0018]

[0019]

[0020]

[0021] This application uses pyridine triazole shown in formula I and boronic acid shown in formula II as substrates, and uses pyrrole or primary amine derived from a new chiral diamine as a catalyst to successfully synthesize a variety of triarylmethanes with high yield and high enantioselectivity. This method not only shows a wide range of substrate applicability and excellent functional group tolerance, but also provides an efficient path for the synthesis of high-value molecules containing chiral C-D bonds, and uses low-cost D2O as a deuterium source to accurately synthesize a series of deuterated derivatives. DETAILED DESCRIPTION

[0022] The present invention is further described in detail below in conjunction with the examples. It should be understood that the examples described in this specification are only for explaining the present invention, not for limiting the present invention, and the parameters, proportions, etc. of the examples can be selected according to local conditions without substantial impact on the results.

[0023] Example 1

[0024] Synthesis of compound 3:

[0025]

[0026] Pyridine triazole compound 1 (0.1mmol), boronic acid compound 2 (0.15mmol), K2CO3 (0.2mmol), chiral catalyst C1 (0.02mmol) and 4.0ml of purified and dried trifluorotoluene were added to a Schlenk tube in sequence, and degassed three times by freeze-thaw-vacuum-argon filling method. The reaction was stirred under argon atmosphere at 25°C, and irradiated for 20 hours from a distance of 2.0cm by a 3W purple LED (λmax=365nm). The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=ratio of 20 / 1 to 5 / 1) to obtain the target compound 3 as a white solid with a melting point of 75.0-76.2°C and a yield of 93%, 96%ee.

[0027] The NMR data of compound 3 are: 1 H NMR(400MHz, CDCl3)δ8.61(dd,J=4.8,0.9Hz,1H),7.59(td,J=7.7,1.8Hz,1H),7.32–7.28(m,2H),7.25– 7.21(m,1H),7.19–7.09(m,6H),6.98(d,J=7.9Hz,1H),6.83(d,J=7.2Hz,1H),5.87(s,1H),2.23(s,3H); 13 C NMR (101 MHz, CDCl3) δ 163.1, 149.6, 142.2, 141.2, 136.8, 136.4, 130.5, 129.5, 129.1, 128.4, 126.6, 126.5, 125.8, 123.8, 121.3, 56.2, 19.9; High resolution: HRMS (ESI) m / z 260.1430 (M+H + ),calc.forC 19 H 17 N + 260.1434.

[0028] Example 2

[0029] Synthesis of compound 4:

[0030] Same as Example 1, except that chiral catalyst C4 is used instead of chiral catalyst C1 in Example 1. Compound 4 is a white solid with a melting point of 77.9-80.8°C and a yield of 96%, 92% ee.

[0031] The NMR data of compound 4 are: 1H NMR (400MHz, CDCl3) δ8.61(d,J=4.3Hz,1H),7.60(td,J=7.7,1.5Hz,1H),7.29(t,J=7.3Hz,2H),7.21(q,J=7.2Hz,3H),7.17 –7.06(m,4H),7.00(d,J=7.9Hz,1H),6.88(d,J=7.7Hz,1H),5.98(s,1H),2.63(qd,J=7.5,1.9Hz,2H),1.12(t,J=7.5Hz,3H); 13 C NMR (101 MHz, CDCl3) δ 163.3, 149.4, 142.7, 142.5, 140.3, 136.4, 129.5, 129.5, 128.6, 128.4, 126.8, 126.4, 125.7, 123.9, 121.3, 55.3, 25.6, 14.9; High resolution: HRMS (ESI) m / z 274.1587 (M+H + ),calc.for C 20 H 19 N + 274.1590.

[0032] Example 3

[0033] Synthesis of compound 14:

[0034] The same as Example 1, except that the chiral catalyst C7 was used instead of the chiral catalyst C1 in Example 1. Compound 14 was a yellow oil with a yield of 93% and 82% ee.

[0035] The NMR data of compound 14 are: 1 H NMR (400MHz, CDCl3) δ8.60(dd,J=4.8,0.8Hz,1H),7.62(td,J=7.7,1.8Hz,1H),7.30(t,J=7.3Hz,2H),7.22(dd,J=8.2,5.8Hz,1H),7. 16(td,J=7.9,4.8Hz,4H),7.10(d,J=7.9Hz,1H),7.04(d,J=7.5Hz,1H),7.00(s,1H),6.95(d,J=7.7Hz,1H),5.70(s,1H),2.29(s,3H); 13C NMR (101 MHz, CDCl3) δ 163.2, 149.6, 142.2, 141.2, 136.9, 136.4, 130.6, 129.6, 129.2, 128.5, 126.6, 126.5, 125.9, 124.0, 121.4, 56.3, 20.0; High resolution: HRMS (ESI) m / z 260.1432 (M+H + ),calc.for C 19 H 17 N + 260.1434.

[0036] Example 4

[0037] Synthesis of compounds 15, 16, 18, and 19:

[0038] Same as Example 1, except that chiral catalyst C8 is used instead of chiral catalyst C1 in Example 1, compound 15 is a yellow oil with a yield of 95%, 90% ee. Product 16 is a yellow oil with a yield of 96%, 83% ee. Product 18 is a yellow oil with a yield of 95%, 86% ee. Product 19 is a yellow oil with a yield of 95%, 85% ee.

[0039] The NMR data of compound 15 are: 1 H NMR (600MHz, CDCl3) δ8.60(d,J=4.3Hz,1H),7.60(td,J=7.7,1.3Hz,1H),7.30(t,J=7.5Hz,2H),7.22(t,J=7.3Hz,1H),7.18(d,J= 7.6Hz,2H),7.15–7.09(m,2H),7.07(d,J=7.7Hz,1H),6.97(s,1H),6.90(d,J=7.7Hz,1H),5.65(s,1H),2.23(s,3H),2.21(s,3H); 13 CNMR (151MHz,CDCl3)δ163.5,149.5,143.0,140.1,136.5,136.3,134.7,130.6,129.6,129.3,128.3,126.7,126.4,123.6,121.3,59.0,19.8,19.3; High resolution: HRMS (ESI) m / z 274.1587 (M+H + ),calc.for C 20 H 19 N + 274.1590.

[0040] The NMR data of compound 16 are: 1 H NMR (400MHz, CDCl3) δ8.60(dd,J=4.8,0.8Hz,1H),7.60(td,J=7.7,1.8Hz,1H),7.30(t,J=7.3Hz,2H),7.22(dd,J =8.4,6.2Hz,1H),7.18(d,J=7.2Hz,2H),7.15–7.07(m,2H),6.87(s,1H),6.79(s,2H),5.64(s,1H),2.26(s,6H); 13 C NMR (101MHz,CDCl3)δ163.4,149.4,142.8,142.5,137.8,136.3,129.3,128.3,128.2,127.2,126.4,123.7,121.3,59.3,21.3; High resolution: HRMS (ESI) m / z 274.1588 (M+H + ),calc.forC 20 H 19 N + 274.1590.

[0041] The NMR data of compound 18 are: 1 H NMR (600MHz, CDCl3) δ8.64(d,J=3.6Hz,1H),7.62(td,J=7.7,1.7Hz,1H),7.40(s,1H),7.32(t,J=7.5Hz,2H),7.30(d,J=2.6Hz,1H),7.24( dd,J=16.2,7.5Hz,3H),7.18–7.14(m,2H),7.13(d,J=8.5Hz,1H),7.05(d,J=3.0Hz,1H),6.43(d,J=3.0Hz,1H),5.88(s,1H),3.80(s,3H); 13 C NMR (151 MHz, CDCl3) δ 164.1, 149.4, 143.6, 136.3, 135.6, 133.7, 129.4, 129.0, 128.5, 128.2, 126.2, 123.8, 123.4, 121.4, 121.2, 109.1, 101.0, 59.4, 32.8; High resolution: HRMS (ESI) m / z 299.1541 (M+H + ),calc.for C 21 H 18 N2 + 299.1543.

[0042] The NMR data of compound 19 are: 1 H NMR (400MHz, CDCl3) δ8.54(d,J=4.1Hz,1H),7.93(d,J=7.8Hz,1H),7.84(s,1H),7.58–7.38(m,6H),7.37 –7.32(m,1H),7.31–7.27(m,2H),7.25–7.20(m,3H),7.18–7.10(m,6H),7.10–7.04(m,2H),5.86(s,1H); 13 C NMR (101 MHz, CDCl3) δ 163.7, 149.2, 143.2, 141.1, 139.7, 137.7, 136.7, 134.3, 129.8, 129.4, 128.4, 127.6, 127.3, 127.0, 126.4, 125.9, 124.0, 123.4, 123.2, 121.4, 120.9, 120.3, 119.8, 109.8, 109.7, 59.2; High resolution: HRMS (ESI) m / z 411.1852 (M+H + ),calc.for C 30 H 22 N2 + 411.1856.

[0043] Example 5

[0044] Synthesis of compound 20:

[0045] The same as Example 1, except that the chiral catalyst C6 is used instead of the chiral catalyst C1 in Example 1. Compound 20 is a yellow oil with a yield of 71% and 90% ee.

[0046] The NMR data of compound 20 are: 1 H NMR(600MHz, CDCl3)δ8.59(d,J=4.4Hz,1H),7.59(td,J=7.7,1.5Hz,1H),7.32–7.28(m,2H),7.21(dd,J=16.7,7.3Hz,3H),7.1 3–7.10(m,1H),7.08(d,J=7.9Hz,1H),5.16(d,J=1.3Hz,1H),4.84(s,1H),2.08–2.01(m,2H),1.96(s,2H),1.65–1.57(m,4H); 13C NMR (151 MHz, CDCl3) δ 162.6, 149.2, 141.5, 139.1, 136.3, 129.8, 129.3, 128.3, 128.0, 126.4, 125.6, 123.6, 121.2, 61.1, 28.9, 25.4, 23.0, 22.3; High resolution: HRMS (ESI) m / z 250.1589 (M+H + ),calc.for C 18 H 19 N + 250.1590.

[0047] Example 6

[0048] Synthesis of compound 30:

[0049] Same as Example 1, except that chiral catalyst C9 is used instead of chiral catalyst C1 in Example 1, K3PO4 is used instead of K2CO3 in Example 1, t-BuPh is used instead of PhCF3 in Example 1, the reaction temperature is -40°C, compound 30 is a yellow oil, the yield is 83%, 94% ee.

[0050] The NMR data of compound 30 are: 1 H NMR (400MHz, CDCl3) δ8.63–8.53(m,1H),8.44(d,J=2.4Hz,1H),8.35(d,J=0.9Hz,1H),7.32(t,J=7.3Hz,2H) ,7.27–7.24(m,1H),7.22–7.16(m,2H),7.16–7.10(m,3H),6.88(d,J=7.2Hz,1H),5.85(s,1H),2.24(s,3H); 13 C NMR (101 MHz, CDCl3) δ 158.6, 145.5, 144.2, 142.4, 140.9, 139.9, 136.5, 130.8, 129.4, 129.1, 128.6, 127.0, 126.9, 126.1, 53.8, 19.9; High resolution: HRMS (ESI) m / z 261.1370 (M+H + ),calc.for C 18 H 16 N2 + 261.1373.

[0051] Example 7

[0052] Synthesis of compound 41:

[0053] The same as Example 1, except that the chiral catalyst C6 is used instead of the chiral catalyst C1 in Example 1. Compound 41 is a yellow oil with a yield of 90%, 90% ee.

[0054] The NMR data of compound 41 are: 1 H NMR (400MHz, CDCl3) δ8.59(dd,J=4.8,0.8Hz,1H),7.58(td,J=7.7,1.8Hz,1H),7.18–7.07(m,4H),7.05(d,J=7.7Hz,1H),6.98(d ,J=7.9Hz,1H),6.88(s,1H),6.86–6.82(m,1H),6.79(dd,J=7.7,1.4Hz,1H),5.78(s,1H),2.23(s,3H),2.21(s,3H),2.19(s,3H); 13 C NMR (101 MHz, CDCl3) δ 163.5, 149.5, 141.4, 139.5, 136.8, 136.5, 136.3, 134.6, 130.8, 130.5, 129.7, 129.1, 126.9, 126.4, 125.8, 123.7, 121.2, 55.9, 20.0, 19.8, 19.4; High resolution: HRMS (ESI) m / z 288.1744 (M+H + ),calc.for C 21 H 21 N + 288.1747.

[0055] Example 8

[0056] Synthesis of compounds 68 and 69:

[0057] Same as Example 1, except that chiral catalyst C8 was used instead of chiral catalyst C1 in Example 1, compound 68 was a yellow oil with a yield of 84% and 81% ee. Compound 69 was a yellow oil with a yield of 87% and 83% ee.

[0058] The NMR data of compound 68 are: 1 H NMR (400MHz, CDCl3) δ8.60(d,J=4.7Hz,1H),7.60(td,J=7.7,1.8Hz,1H),7.19(t,J=7.6H z,1H),7.15–7.00(m,8H),6.96(d,J=7.7Hz,1H),5.64(s,1H),2.33(s,3H),2.30(s,3H); 13C NMR (101 MHz, CDCl3) δ 163.5, 149.4, 142.8, 139.8, 137.9, 136.4, 136.0, 130.0, 129.2, 129.1, 128.2, 127.2, 126.3, 123.7, 121.3, 77.3, 77.0, 76.7, 58.9, 21.5, 21.0; High resolution: HRMS (ESI) m / z 274.1587 (M+H + ),calc.for C 20 H 19 N + 274.1590.

[0059] The NMR data of compound 69 are: 1 H NMR(400MHz, CDCl3)δ8.60(d,J=4.0Hz,1H),7.61(td,J=7.7,1.8Hz,1H),7.24–7.17(m,2H),7.17–7.09(m,2H) ,7.09–7.04(m,2H),7.04–6.90(m,5H),5.66(s,1H),2.60(q,J=7.6Hz,2H),2.30(s,3H),1.19(t,J=7.6Hz,3H); 13 C NMR (101 MHz, CDCl3) δ 163.4, 149.3, 144.3, 142.6, 142.6, 137.9, 136.5, 130.1, 129.0, 128.3, 128.2, 127.2, 126.6, 126.4, 126.0, 123.8, 121.3, 77.3, 77.0, 76.7, 59.3, 28.8, 21.5, 15.5; High resolution: HRMS (ESI) m / z 288.1743 (M+H + ),calc.for C 21 H 21 N + 288.1747.

[0060] Example 9

[0061] Synthesis of compound D-3:

[0062]

[0063] Same as Example 1, except that chiral catalyst C5 is used instead of chiral catalyst C1 in Example 1, and 20.0 times equivalent of D2O of pyridinetriazole compound 1 is added. Compound D-3 is a white solid with Mp 75.0-76.2°C; the yield is 90%, 91% ee, 95% D.

[0064] The NMR data of compound D-3 are: 1 H NMR (400 MHz, CDCl3) δ8.61 (dd, J = 4.8, 0.9 Hz, 1H), 7.59 (td, J = 7.7, 1.9 Hz, 1H), 7.33–7.28 (m, 2H), 7.25–7.20 (m, 1H), 7.17 (dd, J = 11.1, 4.2 Hz, 2H), 7.15–7.10 (m, 3H), 7.09 (s, 1H), 6.98 (d, J = 7.9 Hz, 1H), 6.86–6.81 (m, 1H), 5.87 (s, 0.05H), 2.23 (s, 3H); high resolution: HRMS (ESI) m / z 261.1494 (M+H + ),calc.for C 19 H 16 DN + 261.1497.

[0065] Example 10

[0066] Synthesis of compound D-15:

[0067] Same as Example 10, except that chiral catalyst C8 is used instead of chiral catalyst C5 in Example 10. Compound D-15 is a yellow oil with a yield of 95%, 85% ee, and 93% D.

[0068] The NMR data of compound D-15 are: 1 H NMR (400 MHz, CDCl3) δ8.61 (dd, J = 4.8, 0.9 Hz, 1H), 7.59 (td, J = 7.7, 1.9 Hz, 1H), 7.33–7.28 (m, 2H), 7.25–7.20 (m, 1H), 7.17 (dd, J = 11.1, 4.2 Hz, 2H), 7.15–7.10 (m, 3H), 7.09 (s, 1H), 6.98 (d, J = 7.9 Hz, 1H), 6.86–6.81 (m, 1H), 5.87 (s, 0.07H), 2.23 (s, 3H); high resolution: HRMS (ESI) m / z 275.1648 (M+H + ),calc.for C 20 H 18 DN + 275.1653.

[0069] Embodiment 11

[0070] Synthesis of compound D-20:

[0071] Same as Example 10, except that chiral catalyst C6 is used instead of chiral catalyst C5 in Example 10. Compound D-20 is a yellow oil with a yield of 70%, 83% ee, and 93% D.

[0072] The NMR data of compound D-20 are: 1 H NMR (400 MHz, CDCl3) δ8.58 (dd, J = 4.8, 0.9 Hz, 1H), 7.61–7.54 (m, 1H), 7.30 (ddd, J = 11.8, 5.7, 3.1 Hz, 2H), 7.25–7.17 (m, 3H), 7.14–7.04 (m, 2H), 5.28–5.08 (m, 1H), 4.82 (s, 0.07H), 2.11–1.89 (m, 4H), 1.66–1.58 (m, 4H); high resolution: HRMS (ESI) m / z 251.1647 (M+H + ),calc.for C 18 H 18 DN + 251.1653.

[0073] The preparation of other compounds not specifically described is the same as in Example 1.

[0074] In summary, this application developed for the first time a photochemical asymmetric reaction between pyridine triazole and arylboronic acid, and efficiently synthesized a series of triarylmethanes with potential pharmaceutical value. It is worth mentioning that despite the similarity of the three aromatic groups in spatial configuration, this method still achieved excellent enantioselectivity in most cases, highlighting its precision and efficiency. In addition, this method can regulate the structural characteristics of nitrogen-containing aromatics and significantly improve its synthetic practicability by introducing deuterium atoms at the stereocenter using cheap D2O.

[0075] In general, this application not only provides a versatile and efficient route to obtain these high-value nitrogen-containing aromatic derivatives with precise enantioselectivity, but also achieves two important innovations in expanding chiral hydrogen bond catalysis and utilizing 1,4-boron migration to achieve asymmetric synthesis, laying the foundation for the development of more practical asymmetric reactions.

Claims

1. A method for preparing triarylmethane by asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by chiral primary amine, characterized in that: The synthetic route is as follows: The chiral catalyst used is one of C1 to C9, and the structural formula of C1 to C9 is as follows: The specific process is as follows: Under a protective atmosphere, the pyridine triazole of formula I, the boric acid of formula II and the chiral catalyst are added to an organic solvent, and the reaction is completed by stirring at room temperature to -40°C under visible light irradiation, and the triarylmethane of formula III is obtained by separation and purification; wherein R is H, methyl, F, Cl, Br, CF3 or methoxy, and Ar is 1 for Ar 2 for R 3 represents 1 to 3 identical or different substituents, and each R 3 independently selected from H, F, Cl, Br, C1-C4 saturated alkyl, cyclohexyl, methoxy, CF 3、 Ph, vinyl, ethynyl, Trimethylsilyl or triphenylsilyl, R 4 represents 1 to 3 identical or different substituents, and each R 4 independently selected from F, Cl, Br, methyl, methoxy, CF3, phenyl, ethyl, vinyl, ethynyl or G=N or C.

2. The method according to claim 1, characterized in that The molar ratio of the pyridinetriazole shown in formula I to the boric acid shown in formula II is 1:(1-2), and the amount of the chiral catalyst added is 15-25% of the molar amount of the pyridinetriazole.

3. The method according to claim 1, characterized in that The base is one of K2CO3, KHCO3 and K3PO4 or a mixture of two or more of them in any proportion, and the added amount of the base is 1 to 3 times the molar amount of pyridinetriazole.

4. The method according to claim 1, characterized in that: The organic solvent is one of PhCF3, PhF, PhBr and t-BuPh or a mixture of two or more of them in any proportion.

5. The method according to claim 1, characterized in that The maximum wavelength of visible light is λ max =365nm, visible light is provided by 1 to 2 3W blue LED lamps.

6. The method according to claim 1, characterized in that The method further comprises adding D2O, wherein the amount of D2O added is 15 to 25 times the molar amount of pyridinetriazole.

7. The chiral triarylmethane obtained by the preparation method according to any one of claims 1 to 6.

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