A kind of boron-containing chiral allyl ester compound and high stereoselective synthesis method

Abstract

The present application relates to the technical field of organic synthesis, and particularly relates to a kind of boron-containing chiral allyl ester compound and high stereoselective synthesis method, comprising the following steps: under the action of catalyst, chiral diamine ligand and base, acetylene, boron reagent and alkyl bromide are dissolved in organic solvent and are reacted, and boron-containing chiral allyl ester compound is obtained by separation and purification.The method of the present application uses acetylene, alkyl bromide and double boron reagent, and boron-containing chiral allyl ester compound is prepared by one-step reaction under the synergistic effect of catalyst and diamine ligand, which can not only efficiently synthesize target compound, but also has mild reaction condition, strong substrate universality, good functional group compatibility, excellent chemical selectivity and stereoselectivity, and the highest ee value can reach 95%, the raw materials used are cheap and easy to obtain, and the operation is simple, so that boron-containing chiral allyl ester compound can be efficiently synthesized.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a chiral allyl ester compound containing boron and a high stereoselective synthesis method. BACKGROUND

[0002] Chiral allyl ester fragments are widely present in natural products and biologically active molecules [a) Juagdan, E. G.; Kalidindi, R. S.; Scheuer, P. J.; Borges, M. K. Tetrahedron Letters, 1995, 36, 2905-2908; b) Waelchli, R.; Gamse, R.; Bauer, W.; Lier, E.; Feyen, J. H. M. Bioorg. Med. Chem. Lett. 1996, 6, 1151-1156; c) Meanwell, N. A. J. Med. Chem. 2018, 61, 5822-5880; d) Morand, S.; Jubault, P.; Bouillon, J.-P.; Couve-Bonnaire, S. Chem. Eur. J. 2021, 27, 17273-17279; e) Mandala, S. M.; Thornton, R. A.; Rosenbach, M.; Milligan, J. Garcia-Calvo, M.; Bull, H. G.; Kurtz, M. B. J. Biol. Chem. 1997, 272, 32709-32715; f) Kolter, T.; Sandhoff, K. Angew. Chem. Int. Ed. 1999, 38, 1532-; g) Wakabaya-shi, T.; Mori, K.; Kobayashi, S. J. Am. Chem. Soc. 2001, 123, 1372-1375]. Based on its important application value, the current synthesis methods of chiral allyl ester: [a) Piva, O.; Mortezaei, R.; Henin, F.; Muzart, J.; Pete, J. P. J. Am. Chem. Soc. 1990, 112, 9263-9272 b) Murphy, K. E.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 4690-4691.; c) Suda, T.; Noguchi, K.; Tanaka, K. Angew. Chem. Int. Ed. 2011, 50, 4475-4479; d) Zhou, Y.; Wang, L. F.; Yuan, G. C.; Liu, S. K.; Sun, X.; Yuan, C. N.; Yang, Y. X.; Bian, Q. H.; Wang, M.; Zhong, J. C. Org. Lett. 2020, 22, 4532-4536] But usually need multi-step reaction, the steps are more cumbersome, the stereoselectivity is poor; or limited by raw materials, the substrate range is extremely limited, which does not meet the diversity of chemical synthesis.

[0003] Therefore, it is necessary to study a method for efficiently synthesizing chiral allyl boronate ester compounds, which has simple reaction steps, simple and easily available raw materials, high stereoselectivity, and introduces a boron functional group. SUMMARY

[0004] One of the purposes of the present application is to provide a method for synthesizing chiral allyl boronate ester compounds with high stereoselectivity, which has simple operation, cheap and easily available raw materials, mild reaction conditions, good substrate functional group compatibility, excellent chemical selectivity and stereoselectivity.

[0005] The second purpose of the present application is to provide a chiral allyl boronate ester compound, which is applied to the field of synthesis of bioactive molecule skeletons or drugs.

[0006] The scheme adopted for achieving one of the purposes of the present application is: a method for synthesizing chiral allyl boronate ester compounds with high stereoselectivity, comprising the following steps: dissolving an alkyne, a boron reagent and an alkyl bromide in an organic solvent and reacting under the action of a catalyst, a chiral diamine ligand and a base, and then obtaining a chiral allyl boronate ester compound through separation and purification.

[0007] Preferably, the structure of the alkyne is

[0008] The boron reagent is pinacol diboron;

[0009] The structure of the alkyl bromide is

[0010] The structure of the chiral allyl boronate ester compound is

[0011] wherein R is any one of halogen, ester group, sulfur group, alkoxy group, aryl group, ether group and pyrrole group, R 1 is any one of ester group, sulfur group, aryl group, alkenyl group, amide group, thiophene group and acetal group, R 2 is any one of ethyl group, tert-butyl group, isopropyl group and aryl group.

[0012] Preferably, the chiral diamine ligand is any one of the following compounds:

[0013]

[0014] Preferably, the cation of the base is at least one of Li + , Na + , K + and Cs + ; and the anion of the base is F – , CO32– [CH3COO] – [CF3COO] – [OMe] – [O t Bu] – at least one of the following groups: -OH, -OMe, -OEt, -O

[0015] Preferably, the organic solvent is at least one of tetrahydrofuran, tetrahydropyran, 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, methyl tert-butyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, acetone.

[0016] Preferably, the catalyst is a nickel salt catalyst.

[0017] Preferably, the nickel salt catalyst is any one of NiCl2, NiBr2, NiI2, Ni(OAc)2, Ni(OTf)2, nickel acetylacetonate, nickel bis(benzoylmethyl)acetonate, nickel chloride dimethoxyethane.

[0018] Preferably, the ratio of the catalyst: chiral diamine ligand: boron reagent: base: alkyne: alkyl bromide: organic solvent is 0.014 mmol: 0.014 mmol: 0.8-1.2 mmol: 0.8-1.2 mmol: 0.4 mmol: 0.6-1.2 mmol: 1.0-3.0 mL.

[0019] Preferably, the preparation method of the chiral allyl boronate compound comprises the following steps: dissolving the catalyst and the chiral diamine ligand in a dry organic solvent under an inert gas, then adding the alkyl bromide, the boron reagent, the alkyne, and the base to obtain a reaction mixture, and reacting at 40-60°C until the reaction is complete, then removing the organic solvent, and then purifying the target product chiral allyl boronate compound by column chromatography:

[0020]

[0021] wherein R is any one of halogen, ester group, sulfur group, alkoxy group, aryl group, ether group, pyrrole group, R 1 is any one of ester group, sulfur group, aryl group, alkenyl group, amide group, thiophene group, acetal group, R 2 is any one of ethyl, tert-butyl, isopropyl, aryl group.

[0022] The scheme adopted by the second purpose of the present application is: a chiral allyl boronate compound prepared by the method.

[0023] The synthesis route of the method is as follows:

[0024]

[0025] The present application has the following advantages and beneficial effects:

[0026] 1. The present application provides a method for synthesizing chiral allyl boronate ester compounds with high stereoselectivity, which uses alkynes, alkyl bromides and diboron reagents to prepare chiral allyl boronate ester compounds in one step under the synergistic action of a catalyst and a diamine ligand. The method can not only efficiently synthesize target compounds, but also has mild reaction conditions, strong substrate universality, good functional group compatibility, excellent chemical selectivity and stereoselectivity, and the ee value can reach up to 95%.

[0027] 2. The present application provides a method for synthesizing chiral allyl boronate ester compounds with high stereoselectivity, which uses cheap and readily available raw materials and can efficiently synthesize chiral allyl boronate ester compounds.

[0028] 3. The present application provides a method for synthesizing chiral allyl boronate ester compounds with high stereoselectivity, which synthesizes products containing boron groups, and the target compounds can be further stereoselectively converted to simply and efficiently synthesize other functional chiral allyl ester organic compounds, thereby providing a new method for synthesizing complex drug molecules and drug lead compounds.

[0029] 4. The chiral allyl boronate ester compounds synthesized by the present application are important skeletons in natural products and biologically active molecules, and are also important intermediates for synthesizing drug molecules, and are applied to the fields of biologically active molecule skeletons or drug synthesis. DETAILED DESCRIPTION

[0030] The following examples are further illustrations of the present application, but the scope of the present application is not limited to the following examples.

[0031] In the following examples, the optical rotation value of the chiral compound is measured by a Perkin Elmer 343 polarimeter, the ee value is determined by an Agilent 1260 Series high performance liquid chromatograph, and the HRMS is detected by a Waters Micromass GCT mass spectrometer.

[0032] Example 1

[0033]

[0034] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropryan solvent, then 1-heptyne (52 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)octanoate, a colorless oily liquid, with a yield of 76%; ee = 87%; [a] D 25 = 7.2 (c = 0.93, CHCl3); HPLC detection using Chiralpak OD column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 0.5 mL / min, detection wavelength 254 nm, retention time t R = 9.1 min (minor), 11.1 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 5.3 (s, 1H), 2.8 (dd, J = 9.0, 6.0 Hz, 1H), 2.49 - 2.35 (m, 2H), 1.83 - 1.76 (m, 1H), 1.55 (ddd, J = 13.5, 7.4, 6.0 Hz, 1H), 1.42 - 1.40 (m, 2H), 1.42 (s, 9H), 1.36 - 1.28 (m, 4H), 1.25 (d, J = 1.5 Hz, 12H), 0.90 - 0.87 (m, 6H). 13 C NMR (151 MHz, CDCl3) δ 172.9, 163.8, 82.7, 80.2, 56.5, 35.4, 31.9, 29.5, 28.1, 25.2, 25.0, 24.9, 22.6, 14.2, 12.5; 11 B NMR (128 MHz, Chloroform-d) δ 30.28 ppm; HRMS (ESI) calculated [M+H] + for C 21 H 40 O4B + = 367.3014, found: 367.3014.

[0035] Example 2

[0036]

[0037] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropran solvent, then 4-phenyl-1-butyne (56 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-5-phenyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)pentanoate, colorless oily liquid, yield 71%; ee = 87%; [a] D 25 = +0.5 (c = 1.10, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 0.5 mL / min, detection wavelength 220 nm, retention time t R = 9.5 min (minor), 11.0 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 7.29 (d, J = 4.4 Hz, 4H), 7.22 - 7.14 (m, 1H), 5.38 (s, 1H), 2.94 (dd, J = 9.0, 5.9 Hz, 1H), 2.80 - 2.66 (m, 4H), 1.84 - 1.88 (m, 1H), 1.58 - 1.62 (m, 1H), 1.45 (s, 9H), 1.29 (s, 12H), 0.92 (t, J = 7.3 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 172.8, 162.9, 142.6, 128.6, 128.3, 125.8, 82.9, 80.5, 57.2, 37.8, 36.8, 28.1, 25.0, 25.0, 24.9, 12.4 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 31.45 ppm; HRMS (ESI) calculated [M+H]+ for C 24 H 38 O4B + = 401.2857, found: 401.2852.

[0038] Example 3

[0039]

[0040] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropran solvent, then 3-cyclohexylpropyne (58 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product tert-butyl (S,E)-3-(cyclohexylmethyl)-2-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-3-enoate, white solid, yield 65%; ee = 91%; [a] D 25 = -13.5 (c = 0.63, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 99.7:0.3), flow rate 0.5 mL / min, detection wavelength 220 nm, retention time t R = 10.8 min (minor), 19.4 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 5.34 (s, 1H), 2.79 (dd, J = 9.4, 5.4 Hz, 1H), 2.40 (dd, J = 12.6, 7.5 Hz, 1H), 2.27 (dd, J = 12.6, 6.7 Hz, 1H), 1.84 - 1.72 (m, 1H), 1.69 - 1.63 (m, 5H), 1.57 - 1.50 (m, 1H), 1.48 - 1.43 (m, 1H), 1.41 (s, 9H), 1.24 (s, 12H), 1.21 - 1.11 (m, 3H), 0.97 - 0.90 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H). 13C NMR (151 MHz, CDCI3) δ 172.9, 82.7, 80.1, 55.7, 43.5, 36.7, 33.5, 33.0, 28.1, 26.7, 26.6, 26.6, 25.7, 24.9, 12.6 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.13 ppm; HRMS (ESI) calculated [M+H] + for C 23 H 42 O4B + = 393.3171, found: 393.3171.

[0041] Example 4

[0042]

[0043] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then 4-bromo-n-butynyl (38 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product tert-butyl (S, E)-5-bromo-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)pentanoate, light yellow oily liquid, yield 45%, ee = 92%; [a] D 25 = -7.8 (c = 0.37, CHCI3); HPLC detection using Chiralpak OD column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 1 mL / min, detection wavelength 220 nm, retention time t R = 9.1 min (major), 9.7 min (minor); 1H NMR (600 MHz, Chloroform-d) δ 5.44 (s, 1H), 3.46 - 3.41 (m, 2H), 3.00 - 2.88 (m, 2H), 2.82 (dd, J = 8.7, 6.2 Hz, 1H), 1.77 - 1.83 (m, 1H), 1.59 - 1.50 (m, 1H), 1.42 (s, 9H), 1.26 (s, 12H), 0.87 (t, J = 7.4 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 172.4, 159.0, 83.2, 80.8, 57.1, 38.4, 31.9, 28.1, 25.0, 24.9, 24.9, 12.3 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 29.8 ppm; HRMS (ESI) calculated [M+H] + for C 18 H 33 O4BBr + = 403.1649, found: 403.1645.

[0044] Example 5

[0045]

[0046] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then 6-chlorohexyne (48 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product tert-butyl (S,E)-7-chloro-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)heptanoate, colorless oily liquid, yield 71%; ee = 88%; [a] D 25 = -7.6 (c = 0.46, CHCI3); HPLC detection using Chiralpak IB column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 1.0 mL / min, detection wavelength 220 nm, retention time tR = 5.3 min (minor), 6.1 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 5.31 (s, 1H), 3.55 (t, J = 6.8 Hz, 2H), 2.81 (dd, J = 8.9, 6.0 Hz, 1H), 2.54 - 2.26 (m, 2H), 1.81 - 1.74 (m, 3H), 1.61 - 1.52 (m, 3H), 1.41 (s, 9H), 1.24 (s, 12H), 0.87 (t, J = 7.3 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 172.8, 162.8, 82.9, 80.4, 56.4, 45.0, 34.3, 32.4, 28.1, 26.7, 25.2, 25.0, 24.9, 12.5 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.18 ppm; HRMS (ESI) calculated [M+H] + for C 20 H 37 O4BCl + = 387.2468, found: 387.2463.

[0047] Example 6

[0048]

[0049] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then (but-3-yn-1- yloxy)benzene (52 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-5-phenoxy-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)pentanoate as a colorless oily liquid, yield 55%; ee = 94%; [a] D 25= -5.9 (c = 1.49, CHCh); HPLC detection using Chiralpak AD-H column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 0.5 mL / min, detection wavelength 254 nm, retention time t R = 11.7 min (minor), 14.9 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 7.28 - 7.23 (m, 2H), 6.98 - 6.89 (m, 3H), 5.46 (s, 1H), 4.12 - 4.08 (m, 1H), 4.05 - 4.04 (m, 1H), 3.01 - 2.93 (m, 2H), 2.90 (ddd, J = 12.5, 8.6, 5.9 Hz, 1H), 1.87 - 1.80 (m, 1H), 1.64 - 1.56 (m, 1H), 1.41 (s, 9H), 1.26 (d, J = 1.3 Hz, 12H), 0.90 (t, J = 7.4 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 172.6, 159.1, 158.8, 129.4, 120.5, 114.7, 83.1, 80.6, 67.5, 57.3, 35.2, 28.1, 25.0, 24.9, 24.8, 12.4. ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.08 ppm; HRMS (ESI) calculated [M+H] + for C 24 H 38 O5B + = 417.2807, found: 417.2803.

[0050] Example 7

[0051]

[0052] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then 4-pentyn-1 -carboxylic acid methyl ester (52 ul, 0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product 1-(tert-butyl) 6-methyl (S, E)-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexanedioate as a colorless oily liquid with a yield of 77% and ee = 93%; [a] D 25 = -3.1 (c = 0.62, CHCI3); HPLC detection using Chiralpak IC column, mobile phase n-hexane: isopropanol (volume ratio 97:3), flow rate 1.0 mL / min, detection wavelength 220 nm, retention time t R = 7.1 min (major), 9.6 min (minor); 1 H NMR (400 MHz, Chloroform-d) δ 5.34 (s, 1H), 3.66 (s, 3H), 2.81 (dd, J = 8.7, 6.2 Hz, 1H), 2.77 - 2.62 (m, 2H), 2.49 - 2.40 (m, 2H), 1.83 - 1.75 (m, 1H), 1.55 - 1.52 (ddd, J = 13.7, 7.6, 6.4 Hz, 1H), 1.40 (s, 9H), 1.23 (s, 12H), 0.86 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 173.8, 172.6, 161.3, 83.1, 80.6, 56.9, 51.6, 34.5, 30.5, 28.1, 25.0, 25.0, 24.9, 12.4 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.12 ppm; HRMS (ESI) calculated [M+H] + for C 20 H 36 O6B += 383.2599, found: 383.2596.

[0053] Example 8

[0054]

[0055] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropryan solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and removed from the glove box, and the reaction was carried out at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-6-(naphthalen-2-ylthio)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexanoate: colorless oily liquid, yield 58%; ee = 89%; [a] D 25 = +0.7 (c = 1.10, CHCl3); HPLC detection using Chiralpak OD column, mobile phase n-hexane: isopropanol (volume ratio 99:1), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 6.6 min (minor), 8.8 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 7.77 (d, J = 8.1, 1H), 7.75 - 7.68 (m, 3H), 7.51 - 7.34 (m, 3H), 5.36 (s, 1H), 3.03 (t, J = 7.7 Hz, 2H), 2.82 (dd, J = 8.9, 5.9 Hz, 1H), 2.70 - 2.61 (m, 1H), 2.60 - 2.48 (m, 1H), 1.92 - 1.85 (m, 2H), 1.78 - 1.84 (m, 1H), 1.57 - 1.49 (m, 1H), 1.39 (s, 9H), 1.24 (s, 12H), 0.86 (t, J = 7.4 Hz, 3H). 13C NMR (151 MHz, Chloroform-d) δ 172.7, 162.2, 134.8, 133.9, 131.7, 128.4, 127.8, 127.3, 127.1, 126.6, 126.4, 125.5, 83.0, 80.5, 56.5, 34.8, 33.2, 29.1, 28.1, 25.2, 25.0, 24.9, 12.5. ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.04 ppm; HRMS (ESI) calculated [M+H] + for C 29 H 42 O4BS + = 497.2891, found: 497.2888.

[0056] Example 9

[0057]

[0058] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropran solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-5-((tert-butyldimethylsilyl)oxy)-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)pentanoate: colorless oily liquid, yield 72%; ee = 95%; [a] D 25 = +10.2 (c = 2.80, CHCI3); HPLC detection using Chiralpak OD column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 7.6 min (minor), 11.0 min (major); 1H NMR (600 MHz, Chloroform-d) δ 5.34 (s, 1H), 3.71 (dt, J = 9.7, 7.3 Hz, 1H), 3.62 (dt, J = 9.7, 7.4 Hz, 1H), 2.89 (dd, J = 9.0, 5.8 Hz, 1H), 2.66 (t, J = 7.6 Hz, 2H), 1.84 - 1.72 (m, 1H), 1.60 - 1.48 (m, 1H), 1.41 (s, 9H), 1.24 (d, J = 1.2 Hz, 12H), 0.88 (s, 9H), 0.86 (d, J = 7.3 Hz, 3H), 0.05 (d, J = 2.6 Hz, 6H). 13 CNMR (101 MHz, Chloroform-d) δ 172.8, 160.0, 82.9, 80.4, 63.4, 57.1, 39.2, 28.1, 26.1, 25.0, 25.0, 24.9, 18.5, 12.5, -5.1 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 29.95 ppm; 29 Si NMR (119 MHz, Chloroform-d) δ 18.60 ppm. HRMS (ESI) calculated [M+H] + for C 24 H 48 O5BSi + = 455.3358, found: 455.3353.

[0059] Example 10

[0060]

[0061] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-6-(7-methyl-1H-indol-1-yl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexanoate: colorless oily liquid, yield 91%; ee = 80%; [a] D 25 = -99.5 (c = 1.0, CHCI3); HPLC detection using Chiralpak IB column, mobile phase n-hexane: isopropanol (volume ratio 99:1), flow rate 1 mL / min, detection wavelength 220 nm, retention time t R = 9.0 min (major), 10.7 min (minor); 1 HNMR (600 MHz, Chloroform-d) δ 7.48 (d, J = 7.8 Hz, 1H), 7.08 (d, J = 3.2 Hz, 1H), 6.99 (t, J = 7.5 Hz, 1H), 6.93 (d, J = 7.0 Hz, 1H), 6.49 (s, 1H), 5.39 (s, 1H), 4.36 (td, J = 7.5, 5.2 Hz, 2H), 2.86 (dd, J = 9.0, 5.9 Hz, 1H), 2.78 (s, 3H), 2.65 - 2.47 (m, 2H), 1.98 (p, J = 7.8 Hz, 2H), 1.81 - 1.88 (m, 1H), 1.63 - 1.56 (m, 1H), 1.43 (s, 9H), 1.25 (s, 12H), 0.91 (t, J = 7.3 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 172.6, 162.0, 134.7, 129.8, 129.3, 124.5, 120.7, 119.4, 119.2, 101.5, 83.0, 80.6, 56.6, 48.8, 32.6, 32.4, 28.1, 25.2, 24.9, 24.8, 20.2, 12.4 ppm; 11B NMR (128 MHz, Chloroform-d) δ 29.75 ppm; HRMS (ESI) calculated [M+H] + for C 28 H 43 O4NB + = 468.3280, found: 468,3280.

[0062] Example 11

[0063]

[0064] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product tert-butyl (S,E)-2-ethyl-6-(1H-pyrrol-1-yl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexanoate: yellowish oil liquid, yield 70%; ee = 88%; [a] D 25 = -5.6 (c = 1.20, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 99.5:0.5), flow rate 0.5 mL / min, detection wavelength 254 nm, retention time t R = 13.1 min (minor), 15.8 min (minor); 1HNMR (600 MHz, Chloroform-d) δ 6.67 (t, J = 2.0 Hz, 2H), 6.13 (t, J = 2.0 Hz, 2H), 5.36 (s, 1H), 3.89 (td, J = 7.2, 2.6 Hz, 2H), 2.83 (dd, J = 8.8, 6.1 Hz, 1H), 2.59 - 2.45 (m, 1H), 2.46 - 2.35 (m, 1H), 1.94 (p, J = 7.7 Hz, 2H), 1.81 (ddt, J = 14.4, 8.8, 7.2 Hz, 1H), 1.59 - 1.51 (m, 1H), 1.42 (s, 9H), 1.26 (d, J = 1.3 Hz, 12H), 0.88 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 172.6, 162.2, 120.5, 107.9, 83.0, 80.5, 56.7, 49.7, 32.7, 31.5, 28.1, 25.1, 25.0, 24.9, 12.4 ppm; 11 BNMR (128 MHz, Chloroform-d) δ 30.45 ppm; HRMS (ESI) calculated [M+H] + for C 23 H 39 O4NB + = 404.2967, found: 404.2961.

[0065] Example 12

[0066]

[0067] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product 1-(tert-butyl) 6-((1S,2R,4S)-4,7,7-trimethylbicyclo[2.2.1]heptan-2-yl)(S,E)-2-ethyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexanedioate: colorless oily liquid, yield 65%; [a] D 25 = -16.2 (c = 4.21, CHCl3); 1 H NMR (600 MHz, Chloroform-d) δ 5.36 (s, 1H), 4.93 - 4.88 (m, 1H), 2.86 (dd, J = 8.8, 6.1 Hz, 1H), 2.81 - 2.66 (m, 2H), 2.50 - 2.43 (m, 2H), 2.40 - 2.34 (m, 1H), 1.99 - 1.96 (m, 1H), 1.86 - 1.79 (m, 1H), 1.78 - 1.71 (m, 1H), 1.70 - 1.66 (m, 1H), 1.61 - 1.52 (m, 1H), 1.44 (s, 9H), 1.31 (ddd, J = 12.7, 4.6, 2.2 Hz, 1H), 1.26 (s, 12H), 1.24 - 1.22 (m, 1H), 0.97 (dd, J = 13.8, 3.5 Hz, 1H), 0.91 (s, 3H), 0.91 - 0.87 (m, 6H), 0.84 (s, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 173.4, 172.4, 161.4, 82.9, 80.5, 79.6, 56.7, 48.8, 47.8, 44.9, 36.8, 35.1, 30.6, 28.1, 28.0, 27.1, 25.0, 24.9, 24.8, 19.7, 18.8, 13.5, 12.3. 11B NMR (128 MHz, Chloroform-d) δ 30.2 ppm; HRMS (ESI) calculated [M+H] + for C 29 H 50 O6B + = 505.3699, found: 505.3695.

[0068] Example 13

[0069]

[0070] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and tert-butyl 2-bromobutyrate (148 μL, 0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(tert-butoxycarbonyl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexyl benzoate: colorless oily liquid, yield 80%; ee = 93%; [a] D 25 = -7.3 (c = 0.71, CHCl3); HPLC detection using Chiralpak IC column, mobile phase n-hexane: isopropanol (volume ratio 97:3), flow rate 1.0 mL / min, detection wavelength 254 nm, retention time t R = 5.6 min (major), 10.9 min (minor); 1 H NMR (600 MHz, Chloroform-d) δ 8.03 (d, J = 7.1 Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.8 Hz, 2H), 5.49 (s, 1H), 4.47 (dt, J = 10.7, 6.7 Hz, 1H), 4.39 (dt, J = 10.7, 6.9 Hz, 1H), 3.00 - 2.85 (m, 3H), 1.84 (m, 1H), 1.60 (m, 1H), 1.39 (s, 9H), 1.19 (s, 12H), 0.88 (t, J = 7.3 Hz, 3H) . .13 C NMR (151 MHz, Chloroform-d) δ 172.5, 166.5, 158.6, 132.9, 130.6, 129.7, 128.4, 83.1, 80.6, 64.0, 56.4, 34.7, 28.0, 25.1, 24.9, 24.8, 12.4 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 29.98 ppm; HRMS (ESI) calculated [M+H] + for C 25 H 38 O6B + = 445.2756, found: 445.2753.

[0071] Example 14

[0072]

[0073] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography separation and purification to obtain the product (S,E)-4-(((2,4-dimethylpentan-3-yl)oxy)carbonyl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexyl benzoate: colorless oily liquid, yield 65%; ee = 95%; [a] D 25 = -16.3 (c = 0.66, CHCl3); HPLC detection using Chiralpak OD column, mobile phase n-hexane: isopropanol (volume ratio 97:3), flow rate 1 mL / min, detection wavelength 220 nm, retention time t R = 5.4 min (major), 7.9 min (minor); 1HNMR (600 MHz, Chloroform-d) δ 8.04 (d, J = 6.8 Hz, 2H), 7.56 - 7.50 (m, 1H), 7.41 (t, J = 7.7 Hz, 2H), 5.55 (s, 1H), 4.57 (t, J = 6.1 Hz, 1H), 4.49 - 4.41 (m, 2H), 3.07 (dd, J = 8.5, 6.3 Hz, 1H), 3.02 - 2.98 (m, 1H), 2.94 - 2.89 (m, 1H), 1.96 - 1.91 (m, 1H), 1.81 - 1.86 (m, 2H), 1.58 - 1.70 (m, 1H), 1.19 (s, 12H), 0.90 (t, J = 7.4 Hz, 3H), 0.85 - 0.78 (m, 12H). 13 C NMR (151 MHz, Chloroform-d) δ 173.1, 166.6, 158.5, 132.9, 130.6, 129.8, 128.4, 83.1, 82.9, 64.1, 55.9, 35.1, 29.8, 29.6, 25.1, 24.9, 24.8, 19.7, 19.7, 17.5, 17.2, 12.6. ppm; 11 B NMR (128 MHz, Chloroform-d) δ 29.98 ppm; HRMS (ESI) calculated [M+H] + for C 28 H 44 O6B + = 487.3225, found: 487.3221.

[0074] Example 15

[0075]

[0076] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropryan solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and removed from the glove box, and the reaction was carried out at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(tert-butoxycarbonyl)-6-phenyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexyl benzoate: reddish-brown oily liquid, yield 68%; ee = 92%; [a] D 25 = -7.3 (c = 0.97, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 97.3), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 6.5 min (minor), 7.7 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 8.03 (dd, J = 8.3, 1.4 Hz, 2H), 7.60 - 7.50 (m, 1H), 7.41 (t, J = 7.8 Hz, 2H), 7.27 - 7.21 (m, 2H), 7.21 - 6.97 (m, 3H), 5.53 (s, 1H), 4.43 - 4.39 (m, 2H), 3.08 (dd, J = 9.2, 5.6 Hz, 1H), 2.95 (dt, J = 13.4, 6.8 Hz, 1H), 2.87 (dt, J = 13.3, 6.7 Hz, 1H), 2.64 (ddd, J = 13.6, 10.1, 5.4 Hz, 1H), 2.56 (ddd, J = 13.7, 9.8, 6.4 Hz, 1H), 2.16 - 2.22 (m, 1H), 1.80 - 1.89 (m, 1H), 1.42 (s, 9H), 1.20 (s, 12H). 13C NMR (151 MHz, Chloroform-d) δ 172.3, 166.5, 158.5, 141.7, 132.9, 130.7, 129.8, 128.5, 128.5, 128.4, 126.0, 83.2, 80.9, 64.1, 54.2, 34.7, 34.0, 33.7, 28.1, 24.9, 24.9. ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.50 ppm; HRMS (ESI) calculated [M+H] + for C 31 H 42 O6B+= 521.3069, found: 521.3063.

[0077] Example 16

[0078]

[0079] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(tert-butoxycarbonyl)-6-methyl-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)heptyl benzoate: light yellow oily liquid, yield 61%; ee = 93%; [a] D 25 = -4.7 (c = 1.26, CHCI3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 98:2), flow rate 0.5 mL / min, detection wavelength 210 nm, retention time t R = 5.0 min (minor), 6.8 min (major); 1H NMR (400 MHz, Chloroform-d) δ 8.05 - 8.02 (m, 2H), 7.55 - 7.47 (m, 1H), 7.40 (dd, J = 8.4, 7.0 Hz, 2H), 5.49 (s, 1H), 4.43 (ddt, J = 32.5, 10.7, 6.8 Hz, 2H), 3.14 (dd, J = 9.5, 5.4 Hz, 1H), 2.82 - 2.99 (m, 2H), 1.78 (ddd, J = 13.6, 6.8, 3.7 Hz, 1H), 1.56 - 1.49 (m, 1H), 1.39 (s, 9H), 1.33 - 1.36 (m, 1H), 1.19 (s, 12H), 0.87 (d, J = 6.6 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 172.7, 166.5, 159.0, 132.9, 130.7, 129.8, 128.4, 83.1, 80.6, 64.3, 52.7, 41.1, 34.5, 28.0, 26.3, 24.9, 24.9, 23.1, 22.3. ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.96 ppm; HRMS (ESI) calculated [M+H] + for C 27 H 42 BO6+ = 473.3066, found: 473.3069.

[0080] Example 17

[0081]

[0082] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product 1-(tert-butyl) 5-methyl (S, E)-2-(4-(benzoyloxy)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)but-1-en-2-yl)pentane dioate: colorless oily liquid, yield 55%; ee = 90%; [a] D 25 = +11.6 (c = 0.54, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 97:3), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 12.9 min (minor), 16.7 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 8.03 (d, J = 7.2 Hz, 2H), 7.53 (t, J = 7.4 Hz, 1H), 7.41 (t, J = 7.7 Hz, 2H), 5.48 (s, 1H), 4.44 (ddt, J = 33.9, 10.8, 6.7 Hz, 2H), 3.63 (s, 3H), 3.11 (dd, J = 8.7, 6.3 Hz, 1H), 2.92 (ddt, J = 53.6, 13.2, 6.7 Hz, 2H), 2.40 - 2.23 (m, 2H), 2.12 (dq, J = 14.7, 8.3 Hz, 1H), 1.93 (dq, J = 14.6, 6.7 Hz, 1H), 1.39 (s, 9H), 1.19 (s, 12H). 13 C NMR (151 MHz, Chloroform-d) δ 173.5, 171.9, 166.5, 157.9, 132.9, 130.6, 129.8, 128.4, 83.2, 81.1, 63.8, 53.2, 51.7, 34.8, 31.9, 28.0, 26.8, 24.9, 24.8. 11B NMR (128 MHz, Chloroform-d) δ 30.08 ppm; HRMS (ESI) calculated [M+H] + for C 27 H 40 O8B+=503.2811,found:503.2806.

[0083] Example 18

[0084]

[0085] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and pinacol diboronic acid (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(tert-butoxycarbonyl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)-6-(5-(trimethylsilyl)thiophen-2-yl)hexylbenzoate: colorless oily liquid, yield 52%; ee = 89%; [a] D 25 = -37.3 (c = 0.05, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 99:1), flow rate 0.5 mL / min, detection wavelength 254 nm, retention time t R = 11.5 min (minor), 15.8 min (major); 1H NMR (600 MHz, Chloroform-d) δ 8.04 - 8.01 (m, 2H), 7.53 (s, 1H), 7.41 (t, J = 7.7 Hz, 2H), 7.03 (d, J = 3.3 Hz, 1H), 6.82 (d, J = 3.3 Hz, 1H), 5.52 (s, 1H), 4.46 - 4.36 (m, 2H), 3.12 (dd, J = 9.0, 5.7 Hz, 1H), 3.00 - 2.92 (m, 1H), 2.90 - 2.79 (m, 3H), 2.28 - 2.21 (m, 1H), 1.84 - 1.96 (m, 1H), 1.41 (s, 9H), 1.20 (s, 12H), 0.27 (s, 9H). 13 C NMR (151 MHz, Chloroform-d) δ 172.1, 166.5, 158.3, 150.1, 138.2, 134.1, 132.9, 130.7, 129.8, 128.4, 126.0, 83.2, 81.0, 64.1, 53.9, 34.7, 33.8, 29.9, 28.1, 24.9, 24.9. 0.1 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.59 ppm; 29 Si NMR (119 MHz, Chloroform-d) δ -7.16 ppm; HRMS (ESI) calculated [M+Na] + for C 32 H 47 O6BSSiNa+= 621.2847, found: 621.2835.

[0086] Example 19

[0087]

[0088] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydropryan solvent, then the alkynol (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and removed from the glove box, and the reaction was carried out at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(tert-butoxycarbonyl)-6-(1,3-dioxolan-2-yl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexyl benzoate: yellowish oil liquid, yield 70%; ee = 90%; [a] D 25 = -3.0 (c = 1.40, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 95:5), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 10.6 min (minor), 14.9 min (major); 1 H NMR (600 MHz, Chloroform-d) δ 8.02 (dd, J = 8.3, 1.4 Hz, 2H), 7.53-7.50 (m, 1H), 7.44-7.38 (m, 2H), 5.48 (s, 1H), 4.81 (t, J = 4.6 Hz, 1H), 4.46 (dt, J = 10.7, 6.7 Hz, 1H), 4.39 (dt, J = 10.7, 6.9 Hz, 1H), 3.96-3.86 (m, 2H), 3.83-3.70 (m, 2H), 3.08 (dd, J = 8.8, 6.0 Hz, 1H), 2.95 (dt, J = 13.6, 7.0 Hz, 1H), 2.86 (dt, J = 13.2, 6.7 Hz, 1H), 2.00-1.90 (m, 1H), 1.76-1.67 (m, 1H), 1.66-1.55 (m, 2H), 1.37 (s, 9H), 1.17 (s, 12H). 13CNMR (101 MHz, Chloroform-d) δ 172.2, 166.5, 158.3, 132.8, 130.6, 129.7, 128.3, 104.2, 83.1, 80.8, 64.9, 64.0, 54.2, 34.6, 31.8, 28.0, 26.1, 24.9, 24.8 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 29.94 ppm; HRMS (ESI) calculated [M+H] + for C 28 H 42 O8B+ = 517.2967, found: 517.2967.

[0089] Example 20

[0090]

[0091] In an argon-filled glove box, nickel chloride dimethoxyethane (3.1 mg, 0.014 mmol), L5 (4.4 mg, 0.014 mmol), lithium methoxide (45.3 mg, 1.2 mmol) and bis(pinacolato)diboron (304.8 mg, 1.2 mmol) were dissolved in 1 mL of dry tetrahydrofuran solvent, then the alkyne (0.4 mmol) and alkyl bromide (0.8 mmol) were added, the reaction vial was sealed and taken out of the glove box, and reacted at 50 °C for 24 hours. After the reaction was completed, the reaction solvent was removed by concentration under reduced pressure, and column chromatography was used for separation and purification to obtain the product (S,E)-4-(ethoxycarbonyl)-3-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methylene)hexyl benzoate: yellowish oil liquid, yield 75%; ee = 90%; [a] D 25 = -1.5 (c = 0.25, CHCl3); HPLC detection using Chiralpak AD column, mobile phase n-hexane: isopropanol (volume ratio 95:5), flow rate 1 mL / min, detection wavelength 254 nm, retention time t R = 6.9 min (major), 11.7 min (minor); 1H NMR (600 MHz, Chloroform-d) δ 8.04 (d, J = 6.8 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.8 Hz, 2H), 5.51 (s, 1H), 4.47 - 4.39 (m, 2H), 4.05 - 4.14 (m, 2H), 3.06 (dd, J = 8.7, 6.2 Hz, 1H), 2.92 (t, J = 6.8 Hz, 2H), 1.92 - 1.88 (m, 1H), 1.70 - 1.64 (m, 1H), 1.26 - 1.19 (m, 15H), 0.90 (t, J = 7.3 Hz, 3H); 13 CNMR (151 MHz, Chloroform-d) δ 173.3, 166.6, 158.1, 132.9, 130.6, 129.8, 128.4, 83.2, 64.1, 60.8, 55.7, 34.6, 25.0, 24.93, 24.92, 14.3, 12.4 ppm; 11 B NMR (128 MHz, Chloroform-d) δ 30.09 ppm; HRMS (ESI) calculated [M+H] + for C 23 H 34 O6B + = 417.2443, found: 417.2448.

[0092] Examples 21-24

[0093] Examples 21-24 are different from Example 20 in that L5 is replaced by L1-L4 and L6, after the reaction, the reaction solvent is removed by concentration under reduced pressure, and the product is separated and purified by column chromatography. When the diamine ligand is L1, the product yield is 33%, and the ee value is 67%; when the diamine ligand is L2, the product yield is 43%, and the ee value is 88%; when the diamine ligand is L3, the product yield is 50%, and the ee value is 81%; when the diamine ligand is L4, the product yield is 32%, and the ee value is 82%; and when the diamine ligand is L6, the product yield is 65%, and the ee value is 85%.

[0094]

[0095] The above describes preferred embodiments of the present application, of course, cannot limit the scope of protection of the present application, it should be noted that for ordinary skilled in the art, without departing from the principles of the present application, can make a number of improvements and changes, these improvements and changes are also considered to be within the scope of protection of the present application.

Claims

1. A method for synthesizing boron-containing chiral allyl ester compounds, characterized in that, Includes the following steps: In the presence of a catalyst, a chiral diamine ligand, and a base, alkynes, boron reagents, and alkyl bromides are dissolved in an organic solvent and reacted. After separation and purification, boron-containing chiral allyl ester compounds are obtained. The alkyne is , , , , , , , , , , , , Any one of them; The boron reagent is pinacol diborate; The alkyl bromide is , , , , , , , Any one of them; The boron-containing chiral allyl ester compound is , , , , , , , , , , , , , , , , , , , At least one of them; The chiral diamine ligand is any one of the following compounds: ； The catalyst is a nickel salt catalyst.

2. The method for synthesizing boron-containing chiral allyl ester compounds according to claim 1, characterized in that: The cation of the base is Li. + Na + K + and Cs + At least one of the following; the anion of the base is F. – CO3 2– [CH3COO] – [CF3COO] – [OMe] – [O] t Bu] – At least one of them.

3. The method for synthesizing boron-containing chiral allyl ester compounds according to claim 1, characterized in that: The organic solvent is at least one selected from tetrahydrofuran, tetrahydropyran, 2-methyltetrahydrofuran, 1,4-dioxane, diethyl ether, methyl tert-butyl ether, N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, and acetone.

4. The method for synthesizing boron-containing chiral allyl ester compounds according to claim 1, characterized in that: The nickel salt catalyst is any one of NiCl2, NiBr2, NiI2, Ni(OAc)2, Ni(OTf)2, nickel acetylacetonate, nickel dibenzylidene acetone, and nickel chloride dimethoxyethane.

5. The method for synthesizing boron-containing chiral allyl ester compounds according to claim 1, characterized in that: The molar ratio of catalyst, chiral diamine ligand, boron reagent, base, alkyne, alkyl bromide, and organic solvent is 0.014 mmol: 0.014 mmol: 0.8 – 1.2 mmol: 0.8 - 1.2 mmol: 0.4 mmol: 0.6 - 1.2 mmol: 1.0 - 3.0 mL.

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