A method for preparing triarylmethane by the asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by a chiral primary amine.

Abstract

This invention discloses a method for preparing triarylmethanes via an asymmetric photochemical reaction of chiral primary amine-catalyzed pyridinetriazole and boric acid, belonging to the field of organic synthesis. This application develops a highly efficient modular asymmetric photochemical strategy, with the following synthetic route: The chiral catalyst used is one of C1-C9, with the following structural formulas: Using pyridinetriazole (Formula I) and boric acid (Formula II) as substrates, and employing novel chiral diamine-derived pyrroles or primary amines as catalysts, this application successfully and efficiently synthesized a variety of triarylmethanes with high yields and high enantioselectivity. This method not only demonstrates broad substrate applicability and excellent functional group tolerance, but also utilizes inexpensive D₂O as a deuterium source to precisely synthesize a series of deuterated derivatives, providing an efficient and economical route for synthesizing high-value molecules containing chiral C–D bonds.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis, specifically relating to a method for preparing triarylmethane by a chiral primary amine-catalyzed asymmetric photochemical reaction of pyridinetriazole and boric acid. Background Technology

[0002] The synthesis of enantiomeric triarylmethanes has long been a core research area in asymmetric catalysis, primarily due to its wide applications in medicinal chemistry, fluorescent probes, dyes, and nonlinear optical materials. To date, several efficient methods have been developed for the asymmetric synthesis of electron-rich (nitrogen-containing) aromatic derivatives, such as indoles, pyrroles, and phenols. These strategies typically rely on the generation of electrophilic intermediates from (nitrogen-containing) aromatic derivatives or the direct addition of (nitrogen-containing) aromatics to diaryl-substituted carbocations. However, these methods perform poorly in synthesizing nitrogen-containing aromatic derivatives with electron-deficient ions (such as pyridine) (Zeniou, M.; Fève, M.; Mameri, S.; Dong, J.; Salomé, Chen, W.; EI-Habr, EA; Bousson, F.; Sy, M.; Obszynski, J.; Boh, A.; Villa, P.; Kahn, SA; 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.). It is noteworthy that synthetic examples of these important biomolecules are relatively limited in the literature, and mainly rely on two basic asymmetric transition metal-catalyzed C–H bond functionalization strategies. The first strategy achieves the synthesis of diarylpyridinylmethane through symmetry breaking, specifically by adding a C(sp) group to the ortho-C position of the aryl group. 2 Enantioselective activation occurs at the )–H bond. For example, Yu's research group used chiral complexes constructed from Pd(OAc)2 and L-leucine-derived secondary amino acids 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 enantioselective iridium-catalyzed CH borylation. ACS Catal. 2021, 11, 7339-7349.). The second strategy asymmetrically bonds the C(sp) of arylquinolinylmethanes through reaction with aryl bromides or arylboronic acids. 3 Arylation of the C(sp) –H bond was achieved 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 (Reported by the research group on )-H arylation of 8-benzylquinolines with arylboronic acids. Adv. Synth. Catal. 2024, 366, 774-779.) While these methods are innovative, they have significant limitations in regulating nitrogen-containing aromatic hydrocarbon types, primarily due to the inherent requirement for C–H bond activation. Furthermore, deuteration isotope labeling, crucial in drug discovery, still faces challenges in both of these methods.

[0003] This application presents a novel chiral pyrrole-primary amine catalyst, successfully achieving the synthesis of various triarylmethanes in high yield with excellent enantioselectivity. This method demonstrates a remarkably broad substrate range for controlling aryl and nitrogen-containing aryl substituents. Particularly noteworthy is that this method provides an efficient route for the synthesis of high-value molecules containing chiral C–D bonds, and the use of inexpensive D₂O as a deuterium source shows promising application prospects. Summary of the Invention

[0004] The purpose of this invention is to provide a method for preparing triarylmethane by an asymmetric photochemical reaction of chiral primary amine-catalyzed pyridinetriazole and boric acid.

[0005] To achieve the above objectives, the present invention adopts the following technical solution:

[0006] A method for preparing triarylmethane via an asymmetric photochemical reaction of pyridinetriazole and boric acid catalyzed by a chiral primary amine, the synthetic 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:

[0008]

[0009] The specific process is as follows:

[0010] Under a protective atmosphere, pyridinetriazole (Formula I), boric acid (Formula II), and a chiral catalyst were added to an organic solvent. The reaction was carried out under visible light irradiation at room temperature to -40°C with stirring until complete. The mixture was then separated and purified to obtain triarylmethane (Formula III). In this mixture, R is H, methyl, F, Cl, Br, CF3, or methoxy, and Ar... 1 for

[0011] Ar 2 for R 3 It represents 1 to 3 identical or different substituents, and each R 3 Independently selected from H, F, Cl, Br, C1-C4 saturated alkyl groups, cyclohexyl groups, methoxy groups, CF groups 3、 Ph, vinyl, acetylene Trimethylsilyl or triphenylsilyl, R 4 It 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.

[0012] Furthermore, the molar ratio of pyridinetriazole shown in Formula I to boric acid shown in Formula II is 1:(1-2), and the amount of chiral catalyst added is 15-25% of the molar amount of pyridinetriazole.

[0013] Further, the alkali is one or a mixture of two of K2CO3, KHCO3 and K3PO4 in any proportion, and the amount of alkali added is 1 to 3 times the molar amount of pyridinetriazole.

[0014] Furthermore, the organic solvent is one or a mixture of two of PhCF3, PhF, PhBr and t-BuPh in any proportion.

[0015] Furthermore, the maximum wavelength of the visible light is λ. max =365nm, visible light is provided by 1 to 2 3W blue LEDs.

[0016] Furthermore, it also includes the addition of D2O, the amount of which is 15 to 25 times the molar amount of pyridinetriazole.

[0017] The chiral triarylmethane obtained by the above preparation method.

[0018] Specifically, this application synthesized the following compounds:

[0019]

[0020]

[0021]

[0022]

[0023] This application successfully synthesized a variety of triarylmethanes with high yields and high enantioselectivity using pyridinetriazole (Formula I) and boric acid (Formula II) as substrates and novel chiral diamine-derived pyrroles or primary amines as catalysts. This method not only demonstrates broad substrate applicability and excellent functional group tolerance, but also provides an efficient route for synthesizing high-value molecules containing chiral C–D bonds. Furthermore, it utilizes inexpensive D₂O as a deuterium source to precisely synthesize a series of deuterated derivatives. Detailed Implementation

[0024] The present invention will be further described in detail below with reference to embodiments. It should be understood that the embodiments described in this specification are merely for explaining the present invention and are not intended to limit the present invention. The parameters, proportions, etc. of the embodiments can be selected according to local conditions without having a substantial impact on the results.

[0025] Example 1

[0026] Synthesis of compound 3:

[0027]

[0028] Pyridinetriazole compound 1 (0.1 mmol), boric acid compound 2 (0.15 mmol), K2CO3 (0.2 mmol), chiral catalyst C1 (0.02 mmol), and purified and dried trifluorotoluene (4.0 mL) were sequentially added to a Schlenk tube and degassed three times using a freeze-thaw cycle followed by vacuuming and argon purging. The reaction was stirred at 25 °C under an argon atmosphere and irradiated for 20 hours using a 3W purple LED (λmax = 365 nm) from a distance of 2.0 cm. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate ratio = 20 / 1 to 5 / 1) to obtain target compound 3, a white solid with a melting point of 75.0–76.2 °C, yield of 93%, and 96% ee.

[0029] The NMR data for compound 3 are as follows: 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 (101MHz, 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.

[0030] Example 2

[0031] Synthesis of compound 4:

[0032] 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, a yield of 96%, and 92% ee.

[0033] The NMR data for compound 4 are as follows: 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 (101MHz, 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.

[0034] Example 3

[0035] Synthesis of compound 14:

[0036] Same as Example 1, except that chiral catalyst C7 is used instead of chiral catalyst C1 in Example 1. Compound 14 is a yellow oily substance with a yield of 93% and 82% ee.

[0037] The NMR data for compound 14 are as follows: 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 (101MHz, 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.

[0038] Example 4

[0039] Synthesis of compounds 15, 16, 18, and 19:

[0040] 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% and 90% ee. Product 16 is a yellow oil with a yield of 96% and 83% ee. Product 18 is a yellow oil with a yield of 95% and 86% ee. Product 19 is a yellow oil with a yield of 95% and 85% ee.

[0041] The NMR data for compound 15 are as follows: 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) δ 163.5, 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.

[0042] The NMR data for compound 16 are as follows: 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) δ 163.4, 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.

[0043] The NMR data for compound 18 are as follows: 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 (151MHz, 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.

[0044] The NMR data for compound 19 are as follows: 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 (101MHz, 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.

[0045] Example 5

[0046] Synthesis of compound 20:

[0047] Same as Example 1, except that chiral catalyst C6 is used instead of chiral catalyst C1 in Example 1. Compound 20 is a yellow oily substance with a yield of 71% and 90% ee.

[0048] The NMR data for compound 20 are as follows: 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 (151MHz, 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.

[0049] Example 6

[0050] Synthesis of compound 30:

[0051] 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℃, compound 30 is a yellow oily substance, the yield is 83%, and the ee is 94%.

[0052] The NMR data for compound 30 are as follows: 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 (101MHz, 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.

[0053] Example 7

[0054] Synthesis of compound 41:

[0055] Same as Example 1, except that chiral catalyst C6 is used instead of chiral catalyst C1 in Example 1. Compound 41 is a yellow oily substance with a yield of 90% and 90% ee.

[0056] The NMR data for compound 41 are as follows: 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 (101MHz, 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.

[0057] Example 8

[0058] Synthesis of compounds 68 and 69:

[0059] Same as Example 1, except that chiral catalyst C8 was used instead of chiral catalyst C1 in Example 1. Compound 68 is a yellow oil with a yield of 84% and an ee of 81%. Compound 69 is a yellow oil with a yield of 87% and an ee of 83%.

[0060] The NMR data for compound 68 are as follows: 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 (101MHz, 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.

[0061] The NMR data for compound 69 are as follows: 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 (101MHz, 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.

[0062] Example 9

[0063] Synthesis of compound D-3:

[0064]

[0065] Same as Example 1, except that chiral catalyst C5 is used instead of chiral catalyst C1 in Example 1, and 20.0 equivalents of D2O of pyridinetriazole compound 1 are added. Compound D-3 is a white solid with Mp 75.0-76.2℃; yield is 90%, 91% ee, 95% D.

[0066] The NMR data for compound D-3 are as follows: 1 ¹H NMR (400MHz, CDCl₃) δ 8.61 (dd, J = 4.8, 0.9Hz, 1H), 7.59 (td, J = 7.7, 1.9Hz, 1H), 7.33–7.28 (m, 2H), 7.25–7.20 (m, 1H), 7.17 (dd, J = 11.1, 4.2Hz, 2H), 7.15–7.10 (m, 3H), 7.09 (s, 1H), 6.98 (d, J = 7.9Hz, 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.

[0067] Example 10

[0068] Synthesis of compound D-15:

[0069] 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 oily substance with a yield of 95%, 85% ee, and 93% D.

[0070] The NMR data for compound D-15 are as follows: 1 ¹H NMR (400MHz, CDCl₃) δ 8.61 (dd, J = 4.8, 0.9Hz, 1H), 7.59 (td, J = 7.7, 1.9Hz, 1H), 7.33–7.28 (m, 2H), 7.25–7.20 (m, 1H), 7.17 (dd, J = 11.1, 4.2Hz, 2H), 7.15–7.10 (m, 3H), 7.09 (s, 1H), 6.98 (d, J = 7.9Hz, 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.

[0071] Example 11

[0072] Synthesis of compound D-20:

[0073] 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 oily substance with a yield of 70%, 83% ee, and 93% D.

[0074] The NMR data for compound D-20 are as follows: 1 H NMR (400MHz, CDCl3) δ 8.58 (dd, J = 4.8, 0.9Hz, 1H), 7.61–7.54 (m, 1H), 7.30 (ddd, J = 11.8, 5.7, 3.1Hz, 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.

[0075] The preparation of other compounds, unless otherwise specified, is the same as in Example 1.

[0076] In summary, this application is the first to develop a photochemical asymmetric reaction between pyridinetriazole and arylboronic acid, enabling the efficient synthesis of a series of triarylmethanes with potential pharmaceutical value. Notably, despite the similar spatial configurations of the three aryl groups, this method achieves excellent enantioselectivity in most cases, highlighting its precision and efficiency. Furthermore, this method can control the structural features of nitrogen-containing aromatics and significantly improves its synthetic practicality by introducing deuterium atoms at the stereocenter using inexpensive D₂O.

[0077] Overall, this application not only provides a multifunctional 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 the preparation of triarylmethanes by asymmetric photochemical reaction of pyridine triazoles with boronic acids catalyzed by chiral primary amines, characterized in that, The synthetic route is as follows: The chiral catalyst used is one of C1~C9, and the structural formula of C1~C9 is as follows: ; The specific process is as follows: A pyridine triazole shown in formula I, a boronic acid shown in formula II and a chiral catalyst are added into an organic solvent under a protective atmosphere, the reaction is stirred to completion under visible light irradiation at room temperature to -40°C, and a triarylmethane shown in formula III is obtained by separation and purification; wherein, R is H, methyl, F, Cl, Br, CF3 or methoxy, Ar 1 is , , , , , , , , , or , Ar 2 is , , or , R 3 represents 1-3 Same or Different substituents , and each R 3 is independently selected from H, F, Cl, Br, saturated alkyl of C1-C4, cyclohexyl, methoxy, CF 3、 Ph, vinyl, ethynyl, trimethylsilyl or triphenylsilyl, R 4 represents 1-3 Same or different substituents, The molar ratio of pyridine triazole shown in formula I and boronic acid shown in formula II is 1: (1-2), and the amount of chiral catalyst added is 15-25% of the molar amount of pyridine triazole. , and each R 4 is independently selected from F, Cl, Br, methyl, methoxy, CF3, phenyl, ethyl, vinyl, ethynyl or , G=N or C; the base is one or a mixture of two or more of K2CO3, KHCO3 and K3PO4 in any proportion; the maximum wavelength of the visible light is λ max = 365 nm, and the visible light is provided by 1-2 3W blue LED lamps.

2. The method of claim 1, wherein, The amount of the base added is 1-3 times the molar amount of pyridine triazole.

3. The method of claim 1, wherein, The organic solvent is one of PhCF3, PhF, PhBr and t-BuPh, or a mixture of two or more thereof in any ratio.

4. The method of claim 1, wherein, Also including adding D2O, the amount of D2O added is 15-25 times the molar amount of pyridine triazole.

5. The method of claim 1, wherein, ​

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