Visible light asymmetric catalytic synthesis method of chiral 1, 5-diketone compound

Abstract

The invention discloses a visible light asymmetric catalytic synthesis method of a chiral 1, 5-diketone compound, and belongs to the field of organic synthesis, the synthesis route is as follows: a chiral catalyst adopted by # imgabs 0 is one of C1-C4, and the structural formula of C1-C4 is as follows: # imgabs 1 #; the chiral 1, 5-diketone compound as shown in the formula III is prepared by taking 1, 3-diketone as shown in the formula I and boric acid ester as shown in the formula II as substrates in a protective atmosphere in the presence of a photocatalyst Ir [dF (CF3) ppy] 2 (dtbbpy) PF6 and chiral catalysts C1-C4, so that the chiral 1, 5-diketone compound as shown in the formula III is obtained besides high enantioselectivity; the synthesis strategy has wide practicability in the aspect of efficiently constructing the deuterium-labeled tertiary carbon stereo center with pharmaceutical attraction, and the method provides an efficient way for synthesizing the enantiomerically enriched 1, 5-diketone with the deuterium-labeled stereo center at the site 2.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds. Background Art

[0002] In recent years, the rapid development of green and sustainable platforms, especially the latest progress in visible light-driven photocatalysis, has greatly promoted the research and application of free radical chemistry. This technology enables the efficient synthesis of important molecules under mild conditions using simple and readily available raw materials. However, in free radical reaction systems, the rapid turnover of free radicals and their high reactivity pose a huge challenge to achieving precise enantioselective control of stereocenters through free radical coupling.

[0003] The De Mayo reaction is a classic organic synthesis method that has been widely studied since it was first reported in 1962. The reaction uses readily available 1,3-diketones and alkenes to generate 1,5-diketone compounds through photocatalysis. However, although this reaction mechanism has been developed for more than 60 years, the study of its enantioselective variants did not make a breakthrough until 2023, with only a few successful examples reported. Luo and his team (Zhang, W.; Zhang, L.; Luo, SJ Am. Chem. Soc. 2023, 145, 14227-14232) first developed an asymmetric catalytic method based on direct photoexcitation, using ZrCl4-chiral phosphate complex as a key catalyst to significantly enhance the delocalization of diketo enolate. The system has enhanced photosensitivity, enabling the reaction to be carried out efficiently under visible light drive, effectively avoiding the racemization background reaction under non-acid catalytic conditions. However, the scope of application of this method is relatively limited and is only applicable to the specific 1,2,3,4,5-pentafluoro-6-vinylbenzene when constructing the tertiary stereocenter at the α-position of the ketone.

[0004] In order to overcome this limitation, the inventor and his team (Sun, X.; Liu, Y.; Yin, Y.; Ban, X.; Zhao, X.; Jiang, Z. Asymmetric photoredox catalytic formal de Mayo reaction enabled by sensitivity-initiated electron transfer. Nat. Chem. 2024, 16, 1169-1176.) developed a two-photon sensitization-induced electron transfer strategy, combining a photosensitizer with a dual catalyst system containing pyrene chiral phosphoric acid, and successfully achieved a series of photoredox-neutral De Mayo asymmetric reactions. This method is applicable to a variety of electron-neutral and electron-rich olefins, and exhibits excellent enantioselectivity, significantly broadening the applicability of the reaction.

[0005] Although the above research has made important progress, the development of a universal asymmetric De Mayo reaction applicable to common 1,3-diketones is still a scientific problem that needs to be solved urgently. This reaction needs to be able to introduce a variety of functional groups on the tertiary carbon stereocenter of the product to further expand its application potential in organic synthesis and medicinal chemistry. Therefore, exploring a more efficient, widely applicable and enantioselective De Mayo reaction system has important scientific significance and application value. Summary of the invention

[0006] The purpose of the present invention is to provide a visible light asymmetric catalytic synthesis method for chiral 1,5-diketone compounds.

[0007] Based on the above purpose, the present invention adopts the following technical solutions:

[0008] A visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds, the synthesis route is as follows:

[0009]

[0010] The photocatalyst is Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6

CAS No. 870987-63-6

[0011] The chiral catalyst used is one of C1 to C4, and the structural formula of C1 to C4 is as follows:

[0012]

[0013] The specific preparation process is as follows: under a protective atmosphere, 1,3-diketone represented by formula I, boric acid ester represented by formula II, chiral catalyst and photocatalyst are added to an organic solvent, stirred at room temperature to -30°C under visible light irradiation to complete the reaction, and the chiral 1,5-diketone compound represented by formula III is separated and purified; wherein R 1 C1-C6 alkyl, CF 3 CF 2 H, benzyl, phenethyl, C3-C6 cycloalkyl, Ar 1 for R 2 for Methyl or G1 represents 1 to 3 identical or different substituents, and each G 1 independently selected from H, F, Cl, Br, C1-C4 alkyl, methoxy, G 2 represents 1 to 3 identical or different substituents, and each G 2 independently selected from H, F, Cl, Br, C1-C4 alkyl, methoxy, G 3 represents 1 to 3 identical or different substituents, and each G 3 Independently selected from H, F, Cl, Br, methyl, methoxy or OCF 3 , G 4 represents 1 to 3 identical or different substituents, and each G 4 Independently selected from H, F, Cl, Br, methyl, methoxy or OCF 3 .

[0014] Furthermore, the molar ratio of the 1,3-diketone represented by Formula I, the borate represented by Formula II, the chiral catalyst and the photocatalyst is 1:1:(0.1-0.2):(0.001-0.005).

[0015] Furthermore, the maximum wavelength of the visible light is λmax=420nm, and the visible light is provided by 1 to 2 3W blue LED lamps.

[0016] Furthermore, the method further comprises adding carboxylic acid AD-1, wherein the structural formula of carboxylic acid AD-1 is The amount of carboxylic acid AD-1 added is 0.1 to 1 times the molar amount of 1,3-diketone shown in formula I.

[0017] Furthermore, it also includes adding Molecular sieves: 40-60 mg for every 0.1 mmol of 1,3-diketone of formula I Molecular sieve.

[0018] Furthermore, it also includes adding D 2 O, D 2 The amount of O added is 100 to 200 times the molar amount of the 1,3-diketone shown in formula I.

[0019] Furthermore, the organic solvent is toluene.

[0020] The chiral 1,5-diketone compound prepared by the above preparation method.

[0021] Specifically, the present application synthesized the following compounds:

[0022]

[0023]

[0024]

[0025] This application uses a series of 1,3-diketones to react with 2-(1-phenylvinyl)-1,3,2-dioxaborane. The results show that these reactions are carried out efficiently, and the yields of the target products 3-37 are between 31% and 92%, and the ee values ​​are between 53% and 95%. In most cases, the reactions show excellent enantioselectivity and high yields. The substrate adaptability of 1,3-diketones shows significant diversity, and the 1-position can contain aromatic groups with different electron-withdrawing or electron-donating groups, or fused aromatic ring structures. In addition to linear or cyclic alkyl and aryl groups, polyfluoroalkyl groups such as CF 3 and CF 2 H is also well tolerated at the 3-position. It is noteworthy that the chiral catalyst pseudo-enantiomers C2 and C4 can generate two enantiomers (i.e., products 20 and 21) with high enantioselectivity, further demonstrating the practicality of this synthetic method. However, some products (such as 14, 16, 17, 19, 34, and 37) have low yields, mainly due to their significantly slow reaction process. In addition, the ortho-substituents on the aromatic group (such as product 34) may slow down the reaction rate and reduce the enantioselectivity due to significant steric hindrance.

[0026] Subsequently, this application examined the scope of application of olefins. Taking 1-phenylbutane-1,3-dione as a representative of 1-aryl-3-alkyl diones, it reacted with a variety of α-aryl-α-boronic ester olefins to produce a series of 1,5-diketone products containing 2-aryl (38-43) or 2-heteroaryl (44-45), with yields ranging from 40% to 70% and ee values ​​ranging from 90% to 92%. In addition, the study found that 1,3-diaryl diones represented by 1,3-diphenylpropane-1,3-dione can efficiently synthesize products with substituents at the C-2 position (46-55), showing high yields and enantioselectivities over a wide range of substrates.

[0027] Further testing of various α-boronic acid ester olefins containing alkyl or benzyl groups at the α position, and the reaction with substrate 1, the products (56-60) were generated in yields between 60% and 80% and ee values ​​between 81% and 93%. The robustness of this approach was further verified by the introduction of the drug molecules oxaprozin (61) and isoxazole Paque (62), and the target products of great significance were successfully constructed.

[0028] In addition to achieving high enantioselectivity, this synthetic strategy also shows broad applicability for constructing deuterium-labeled tertiary stereocenters in medicinal chemistry. 2In the presence of O, a series of asymmetric De Mayo reactions were carried out to evaluate its universality, and a variety of representative deuterated products (such as D1-3, D1-26, D1-20, D1-24, and D1-25) were successfully synthesized, which showed high enantioselectivity and excellent deuterium incorporation rate. In addition, D1-20 and D1-26 were selected to react with Et 3 The corresponding products D2-20 and D2-26 were obtained in high yields and maintained the original ee values. This method provides a new route with potential application value for the efficient synthesis of enantioenriched 1,5-diketones with a deuterium-labeled stereocenter at the C-2 position. DETAILED DESCRIPTION

[0029] 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.

[0030] Example 1

[0031] Synthesis of compound 3:

[0032]

[0033] In a 25 mL Schlenk tube, add 60 μL (0.0003 mmol, 0.003 eq) of Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 Solution (composed of 11.2 mg of Ir[dF(CF 3 )ppy] 2 (dtbbpy)PF 6 Dissolved in 2.0 mL of anhydrous toluene), then remove the solvent under vacuum. 1-Phenylbutane-1,3-dione 1 (0.1 mmol, 1.0 equivalent), α-boronic acid styrene 2 (0.1 mmol, 1.0 equivalent), chiral catalyst C1 (0.01 mmol, 0.1 equivalent), AD-1 (0.01 mmol, 0.1 equivalent), Molecular sieves (50 mg) and toluene (5.0 mL), followed by three degassings by freeze-vacuum-thaw method. The reaction mixture was stirred under an argon atmosphere at -20 ° C and irradiated with a 3W blue LED lamp (wavelength λmax = 420 nm) at a distance of 7.0 cm for 72 hours. The solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (volume ratio, petroleum ether / ethyl acetate = 20 / 1 to 5 / 1 ratio) to obtain the target compound 3 as a white solid, Mp 87.3-88.8 ° C, a yield of 78%, 91% ee.

[0034] The NMR data of compound 3 are: 1 H NMR (300 MHz, CDCl 3 )δ7.95(d,J=7.4Hz,2H),7.47(t,J=7.3Hz,1H),7.37(t,J=7.5Hz,2H),7.28(q,J=4.5,3. 6Hz,4H),7.25–7.16(m,1H),4.65(t,J=6.9Hz,1H),2.51–2.31(m,3H),2.20–2.00(m,4H); 13 C NMR (75MHz, CDCl 3 )δ208.4,199.5,139.0,136.5,132.9,129.0,128.7,128.5,128.2,127.2,52.2,40.9,30.0,27.6.

[0035] The synthesis of compounds 2-14, 26-32, and 37 is the same as compound 1.

[0036] Example 2

[0037] Synthesis of compound 15:

[0038] Same as Example 1, except that a 3W blue LED lamp (wavelength λmax=420nm) was used for irradiation at a distance of 5.0cm for 96 hours. Compound 15 was a white solid with Mp 71.3-72.9°C and a yield of 57% and 92%ee.

[0039] The NMR data of compound 15 are: 1 H NMR (300 MHz, CDCl 3 )δ7.86(d,J=7.7Hz,2H),7.41(t,J=7.3Hz,1H),7.36–7.04(m,12H),4.55(t,J= 7.1Hz,1H),3.57(s,2H),2.50–2.26(m,3H),2.04(dq,J=13.7,6.9,6.1Hz,1H); 13C NMR (75MHz, CDCl 3 )δ207.9,199.5,138.9,136.6,134.1,132.8,129.3,128.9,128.7,128.4,128.2,127.1,127.0,52.0,50.1,39.2,27.6.

[0040] The synthesis of compounds 16, 17, 18 and 19 was the same as compound 15.

[0041] Example 3

[0042] Synthesis of compound 20:

[0043] Same as Example 1, except that chiral catalyst C2 is used instead of chiral catalyst C1 in Example 1, and AD-1 and Molecular sieves, compound 20 is a white solid, Mp 41.1-43.0 °C, the yield is 66%, 93% ee.

[0044] The NMR data of compound 20 are: 1 H NMR (300 MHz, CDCl 3 )δ7.94(d,J=7.7Hz,2H),7.49(t,J=7.3Hz,1H),7.44–7.16(m,7H),4.64(t,J=7.4Hz,1 H),2.73(t,J=7.0Hz,2H),2.49(dq,J=14.3,7.2Hz,1H),2.25(dq,J=14.2,7.1Hz,1H); 19 F NMR (471 MHz, CDCl 3 )δ–79.23; 13 C NMR (75MHz, CDCl 3 )δ198.7,191.3(q,J=35.1Hz),138.3,136.3,133.1,129.3,128.7,128.6,128.1,127.6,115.4(q,J=292.2Hz),51.9,34.0,26.3.

[0045] The syntheses of compounds 22, 23, 24 and 25 were the same as compound 20.

[0046] Example 4

[0047] Synthesis of compound 21:

[0048] Same as Example 1, except that chiral catalyst C4 is used instead of chiral catalyst C1 in Example 1, 3W blue LED light (wavelength λmax=420nm) is used for irradiation at a distance of 3.0cm, and AD-1 and Molecular sieves, compound 21 is the enantiomer of compound 20, with a yield of 87% and 91% ee.

[0049] Example 5

[0050] Synthesis of compound 33:

[0051] Same as Example 1, except that the reaction was carried out at -30°C for 96 h. Compound 33 was a white solid with Mp 94.6-95.8°C and a yield of 83% and 87% ee.

[0052] The NMR data of compound 33 are: 1 H NMR (300 MHz, CDCl 3 )δ7.68–7.44(m,4H),7.43–7.18(m,7H),7.08(dd,J=19.0,8.0Hz,2H),4.78(t,J=7.3Hz,1H),3.84(d,J =12.2Hz, 6H), 2.99 (qt, J = 17.1, 6.8Hz, 2H), 2.62 (dq, J = 14.0, 7.1Hz, 1H), 2.31 (dq, J = 13.5, 6.6Hz, 1H); 13 CNMR (75MHz, CDCl 3 )δ199.6,199.3,159.7,159.6,139.1,138.1,137.9,129.5,129.4,129.0,128.2 ,127.2,121.3,120.6,119.5,119.4,112.9,112.1,55.3,55.3,52.5,36.1,28.3.

[0053] The synthesis of compounds 35 and 36 was the same as compound 33.

[0054] Example 6

[0055] Synthesis of compound 34:

[0056] Same as Example 1, except that the reaction was carried out at 25°C and irradiated with a 3W blue LED lamp (wavelength λmax=420nm) at a distance of 3.0cm. Compound 34 was a white solid with Mp 75.3-77.1°C and a yield of 32% and 53%ee.

[0057] The NMR data of compound 34 are: 1 H NMR (300 MHz, CDCl3 )δ7.63(d,J=7.4Hz,1H),7.55(d,J=7.5Hz,1H),7.51–7.10(m,11H),4.65( t,J=7.4Hz,1H),3.11–2.81(m,2H),2.71–2.46(m,4H),2.46–2.23(m,4H); 13 C NMR (75MHz, CDCl 3 )δ204.0,203.7,138.5,138.2,137.9,137.9,137.9,131.9,131.6,131.2,130.9 ,128.9,128.5,128.3,127.9,127.3,125.6,125.4,55.4,38.9,27.6,21.2,20.8.

[0058] Example 7

[0059] Synthesis of compound 56:

[0060] Same as Example 1, except that the reaction was carried out at 25°C, the amount of AD-1 added was 0.1 mmol (1.0 equiv), and irradiation was performed with a 3W blue LED lamp (wavelength λmax=420 nm) at a distance of 3.0 cm. Compound 56 was a yellow oily liquid with a yield of 60%, 81% ee.

[0061] The NMR data of compound 56 are: 1 H NMR (300 MHz, CDCl 3 )δ8.03–7.92(m,2H),7.60–7.52(m,1H),7.46(t,J=7.4Hz,2H),3.55(h,J=6.9Hz,1H),2.44( ddt,J=31.9,17.5,8.0Hz,2H),2.20–1.97(m,4H),1.83–1.65(m,1H),1.19(d,J=6.9Hz,3H); 13 C NMR (75MHz, CDCl 3 )δ208.4,203.8,136.3,133.0,128.7,128.3,40.8,39.4,29.9,27.1,17.5.

[0062] Example 8

[0063] Synthesis of compound 57:

[0064] Same as Example 1, except that chiral catalyst C3 is used instead of chiral catalyst C1 in Example 1, and AD-1 and Molecular sieve, reaction temperature is 25°C, compound 57 is a yellow oily liquid, the yield is 82%, 90% ee. The NMR data of compound 57 are: 1 H NMR (300 MHz, CDCl 3 )δ7.74(d,J=7.7Hz,2H),7.39(t,J=7.3Hz,1H),7.28(t,J=7.3Hz,2H),7.15–6.95(m,5H),3.69(p,J=6.8Hz,1H),2.97(dd,J=13.8,7.2H z,1H),2.60(dd,J=13.8,7.0Hz,1H),2.33(dt,J=15.4,7.3Hz,1H),2.23–2.09(m,1H),2.01–1.82(m,4H),1.74(tt,J=12.8,5.8Hz,1H); 13 C NMR (75MHz, CDCl 3 )δ208.0,203.3,139.2,137.1,133.1,128.9,128.6,128.4,128.2,126.3,46.7,40.6,38.3,29.8,25.7.

[0065] The syntheses of compounds 58, 59, 60, 61 and 62 were the same as compound 57.

[0066] Example 9

[0067] Synthesis of compounds D1-3, D1-20, D1-24, D1-25, D1-26:

[0068]

[0069] Same as Example 1, except that 10 mmol to 20 mmol D 2 O, that is, the target compound is obtained.

[0070] D1-3, a white solid, Mp 89.1-90.8 °C, yield 79%, 87% ee, D 1 =93%,D 2 +D 3 =183%.

[0071] D1-20, a white solid, Mp 45.3-46.6 °C, yield 74%, 95% ee, D 1 =93%,D 2 +D 3 =187%.

[0072] D1-24, yellow solid, Mp 79.7-81.3 °C, yield 86%, 95% ee, D 1 =93%,D 2 +D 3 =186%.

[0073] D1-25, a white solid, Mp 53.3-54.9 °C, yield 57%, 95% ee, D 1 =91%,D 2 +D 3 =182%.

[0074] D1-26, a white solid, Mp 85.1-86.9 °C, yield 73%, 87% ee, D 1 =92%,D 2 +D 3 =186%.

[0075] The NMR data of compound D1-3 are: 1 H NMR (300 MHz, CDCl 3 )δ7.95(d,J=7.5Hz,2H),7.48(t,J=7.2Hz,1H),7.38(t,J=7.5Hz,2H),7.34–7.25(m,4H),7 .24–7.16(m,1H),4.64(t,J=7.4Hz,0.07H),2.37(d,J=14.1Hz,1.17H),2.21–1.96(m,4H); 13 C NMR (75MHz, CDCl 3 )δ208.6,199.5,138.9,136.5,132.9,129.0,128.7,128.5,128.2,127.2,52.1,40.5,30.0,27.4.

[0076] The NMR data of compound D1-20 are: 1 H NMR (300 MHz, CDCl 3 )δ7.94(d,J=7.7Hz,2H),7.55–7.45(m,1H),7.43–7.16(m,7H),4.63(t,J=7.4Hz ,0.07H),2.77–2.63(m,0.13H),2.47(d,J=14.2Hz,1H),2.23(d,J=14.2Hz,1H); 19 F NMR (471 MHz, CDCl 3 )δ–79.29; 13 C NMR (75MHz, CDCl 3)δ198.7,191.4(q,J=35.1Hz),138.2,136.2,133.1,129.3,128.7,128.6,128.1,127.6,115.4(q,J=292.0Hz),51.8,33.8,26.0.

[0077] The NMR data of compound D1-24 are: 1 H NMR (300 MHz, CDCl 3 )δ8.48(s,1H),8.01(d,J=8.6Hz,1H),7.91(d,J=7.8Hz,1H),7.82(d,J=8.9Hz,2H),7.54(dt,J=15.0,6.8Hz,2H),7.39–7.28 (m,4H),7.28–7.18(m,1H),4.81(t,J=7.4Hz,0.07H),2.82–2.70(m,0.14H),2.54(d,J=14.2Hz,1H),2.30(d,J=14.2Hz,1H); 19 F NMR (471 MHz, CDCl 3 )δ–79.23; 13 C NMR (75MHz, CDCl 3 )δ198.7,191.5(q,J=35.3Hz),138.3,135.5,133.5,132.3,130.6,129.6,129.3,128. 6,128.4,128.1,127.6,127.6,126.7,124.3,115.4(q,J=292.1Hz),51.9,33.9,26.0.

[0078] The NMR data of compound D1-25 are: 1 H NMR (300 MHz, CDCl 3 )δ7.95(d,J=7.3Hz,2H),7.53–7.43(m,1H),7.43–7.12(m,7H),5.65(t,J=53.9Hz,1H),4.63 (t,J=7.4Hz,0.09H),2.69–2.58(m,0.18H),2.44(d,J=14.2Hz,1H),2.19(d,J=14.2Hz,1H); 19 F NMR (471 MHz, CDCl 3 )δ–127.04; 13 C NMR (75MHz, CDCl 3)δ199.6(t,J=26.1Hz),199.0,138.4,136.3,133.1,129.2,128.7,128.5,128.1,127.4,109.6(t,J=252.8Hz),52.0,33.6,26.0.

[0079] The NMR data of compound D1-26 are: 1 H NMR (300 MHz, CDCl 3 )δ7.98(d,J=7.4Hz,2H),7.90(d,J=7.4Hz,2H),7.60–7.15(m,11H),4.78(t,J=7.3Hz,0 .08H),2.94(dt,J=23.4,6.3Hz,0.14H),2.57(d,J=14.0Hz,1H),2.27(d,J=13.9Hz,1H); 13 C NMR (75MHz, CDCl 3 )δ200.0,199.6,139.0,136.7,136.6,133.0,132.9,129.0,128.7,128.5,128.5,128.3,128.0,127.2,52.5,35.9,28.1.

[0080] Example 10

[0081] Synthesis of compound D2-20:

[0082]

[0083] D1-20 (32.3 mg, 0.1 mmol, 1.0 equivalent) was added to a 25 mL round-bottom flask, followed by dichloromethane (5 mL). Then triethylamine (Et 3 N, 13.9 μL, 0.1 mmol, 1.0 equiv) and H 2 O (90 μL, 5 mmol, 50 equivalents). The reaction mixture was stirred at 25 ° C for 12 hours. The crude product was freed from the solvent under reduced pressure, and the residue was purified by silica gel column chromatography (volume ratio, petroleum ether / ethyl acetate = 8:1) to obtain D2-20 as a white solid, Mp 44.9-46.4 ° C, yield 84%, 91% ee, D = 90%.

[0084] The NMR data of compound D2-20 are: 1 H NMR (300 MHz, CDCl 3)δ7.94(d,J=7.5Hz,2H),7.49(t,J=7.3Hz,1H),7.43–7.08(m,7H),4.64(t,J=7.4Hz,0. 1H), 2.73 (t, J=6.9Hz, 2H), 2.48 (dt, J=14.1, 7.1Hz, 1H), 2.24 (dt, J=13.9, 6.7Hz, 1H); 19 F NMR (471 MHz, CDCl 3 )δ–79.23; 13 C NMR (75MHz, CDCl 3 )δ198.7,191.3(q,J=35.2Hz),138.1,136.2,133.1,129.3,128.7,128.6,128.1,127.6,115.4(q,J=292.2Hz),51.8,33.9,26.1.

[0085] Embodiment 11

[0086] Synthesis of compound D2-26:

[0087]

[0088] A 25 mL round-bottom flask was charged with D1-26 (28.0 mg, 0.1 mmol, 1.0 eq.), followed by THF (5 mL). Pyrrolidine (3.6 mg, 0.05 mmol, 0.5 eq.) and H 2 O (720 μL, 40 mmol, 400 equiv). The reaction mixture was stirred at 50°C for 36 hours. The crude product was freed from the solvent under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 20:1) to obtain D2-26 as a white solid, Mp 89.1-90.3°C, yield 93%, 82% ee, D = 86%.

[0089] The NMR data of compound D2-26 are: 1 H NMR (300 MHz, CDCl 3 )δ7.99(d,J=7.5Hz,2H),7.90(d,J=7.5Hz,2H),7.61–7.15(m,11H),4.78(t,J=7.3Hz,0.14H), 2.96(tq,J=17.2,8.3,6.6Hz,2H), 2.59(dt,J=13.8,6.9Hz,1H), 2.28(dt,J=13.6,6.6Hz,1H); 13 C NMR (75MHz, CDCl 3)δ199.9,199.6,139.0,136.7,136.5,133.0,132.9,129.0,128.7,128.5,128.5,128.3,128.0,127.2,52.4,35.9,28.1.

[0090] Application Examples

[0091]

[0092] Compound 57 (28.0 mg, 0.1 mmol, 1.0 equiv) was added to a 25 mL round-bottom flask, followed by THF (5 mL). The resulting solution was cooled to 0°C, and sodium hydride (NaH, 4.8 mg, 0.2 mmol, 2.0 equiv) was added. The reaction mixture was stirred at 25°C for 1 hour. The crude product was purified by column chromatography (n-hexane / ethyl acetate = 20:1) to give compound 96 as a colorless oil with a yield of 95%, 90% ee.

[0093] The NMR data of compound 96 are: 1 H NMR (300 MHz, CDCl 3 )δ7.59(dd,J=6.4,2.9Hz,2H),7.53–7.41(m,3H),7.36–7.13(m,5H),6.33(s,1H),3.28(dq,J=11.4,3.9H z,1H),2.86(dd,J=13.9,3.8Hz,1H),2.73–2.51(m,2H),2.41(dt,J=17.5,4.1Hz,1H),2.20–1.89(m,2H); 13 C NMR (75MHz, CDCl 3 )δ199.5,163.7,139.6,138.1,130.0,129.0,128.7,128.6,126.7,126.5,125.8,38.4,37.4,32.6,24.6.

Claims

1. A visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds, characterized in that: The synthetic route is as follows: The photocatalyst is Ir[dF(CF3)ppy]2(dtbbpy)PF6, and the chiral catalyst used is one of C1 to C4. The structural formula of C1 to C4 is as follows: The specific preparation process is as follows: under a protective atmosphere, 1,3-diketone represented by formula I, boric acid ester represented by formula II, chiral catalyst and photocatalyst are added to an organic solvent, stirred at room temperature to -30°C under visible light irradiation to complete the reaction, and the chiral 1,5-diketone compound represented by formula III is separated and purified; wherein R 1 C1-C6 alkyl, CF3, CF2H, benzyl, phenethyl, C3-C6 cycloalkyl, Ar 1 for R 2 for Methyl or G 1 represents 1 to 3 identical or different substituents, and each G 1 independently selected from H, F, Cl, Br, C1-C4 alkyl, methoxy, G 2 represents 1 to 3 identical or different substituents, and each G 2 independently selected from H, F, Cl, Br, C1-C4 alkyl, methoxy, G 3 represents 1 to 3 identical or different substituents, and each G 3 independently selected from H, F, Cl, Br, methyl, methoxy or OCF3, G 4 represents 1 to 3 identical or different substituents, and each G 4 Independently selected from H, F, Cl, Br, methyl, methoxy or OCF3.

2. The visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds according to claim 1, characterized in that: The molar ratio of the 1,3-diketone shown in formula I, the boric ester shown in formula II, the chiral catalyst and the photocatalyst is 1:1:(0.1-0.2):(0.001-0.005).

3. The visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds according to claim 1, characterized in that: The maximum wavelength of visible light is λ max =420nm, visible light is provided by 1 to 2 3W blue LED lamps.

4. The visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds according to claim 1, characterized in that: The invention also includes adding carboxylic acid AD-1, the structural formula of which is The amount of carboxylic acid AD-1 added is 0.1 to 1 times the molar amount of 1,3-diketone shown in formula I.

5. The visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds according to claim 1, characterized in that: It also includes adding Molecular sieves: 40-60 mg for every 0.1 mmol of 1,3-diketone of formula I Molecular sieve.

6. The method according to claim 1, characterized in that The method further comprises adding D2O, wherein the amount of D2O added is 100 to 200 times the molar amount of the 1,3-diketone shown in formula I.

7. The visible light asymmetric catalytic synthesis method of chiral 1,5-diketone compounds according to claim 1, characterized in that: The organic solvent is toluene.

8. A chiral 1,5-diketone compound obtained by the preparation method according to any one of claims 1 to 7.

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