A method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, aryl boronic acids

Abstract

The application discloses a method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters and aryl boronic acids, and belongs to the field of organic synthesis. The method comprises the following steps: dissolving a copper catalyst and a bisoxazoline ligand in a mixed solvent, stirring uniformly, adding unsaturated hydrocarbon substrates, oxime ester substrates and aryl boronic acid compounds, and reacting at 0 DEG C for 12-32 hours; the unsaturated hydrocarbon substrates comprise one of olefin compounds, 4-aryl-1,3 enyne compounds or 4-alkyl-1,3 enyne compounds; when the unsaturated hydrocarbon substrates are 4-aryl-1,3 enyne compounds, the reaction is carried out under ultraviolet light irradiation; and when the unsaturated hydrocarbon substrates are 4-alkyl-1,3 enyne compounds, the reaction is carried out under blue light irradiation. By combining the strategies of photocatalysis and copper catalysis, the substrate range is expanded to enyne compounds, and the high-value conversion of low-cost unsaturated hydrocarbons such as olefins and enynes to chiral aryl compounds can be realized.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and more specifically to a method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids. Background Technology

[0002] Chiral aryl units are not only widely found in natural products and drug molecules, but also play multiple roles in organic synthesis, including catalysts, ligands, and synthons. For example, chiral 1,1-diarylalkanes (such as tolterodine and escitalopram) serve as drug molecules, aryl-substituted allenes act as chiral catalysts and chiral ligands, and benzyl alkynes (such as PLA inhibitors) exhibit physiological activity. Therefore, developing efficient and practical catalytic strategies to introduce chiral aryl units is of great importance and has attracted increasing research interest from organic chemists and medicinal chemists.

[0003] In recent years, research on transition metal-catalyzed asymmetric arylation reactions has been developing, but it still faces some challenges, such as demanding reaction conditions (requiring organometallic reagents) and a limited substrate range (mostly focused on olefin conversion), which restricts the diversity of target molecules.

[0004] Therefore, it is of great significance to provide a synthetic method for chiral aryl compounds, develop a general arylation system, expand the substrate range to previously unreported enyne substrates, and realize the modular synthesis of various chiral arylated compounds, including 1,1-diarylalkanes, arylalkynes, and axially chiral allenes. Summary of the Invention

[0005] To address the shortcomings of existing technologies, one objective of this invention is to provide a method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids. Using olefins, alkenynes, oxime esters, and arylboronic acids as raw materials, this method efficiently and selectively synthesizes chiral diarylalkanes, chiral arylynes, or chiral allenes, achieving a high-value transformation of unsaturated hydrocarbons such as olefins and alkenynes into chiral products. Furthermore, the synthesis method of this invention features mild reaction conditions, a simple synthetic route, and high efficiency.

[0006] The objective of this invention is achieved through the following technical solutions.

[0007] A method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids includes the following steps:

[0008] The copper catalyst and the bisoxazoline ligand were dissolved in a mixed solvent and stirred until homogeneous. Unsaturated hydrocarbon substrates, oxime ester substrates and arylboronic acid compounds were added, and the reaction was carried out at 0°C for 12–32 h.

[0009] The unsaturated hydrocarbon substrate includes one of olefins, 4-aryl-1,3-enyne compounds, or 4-alkyl-1,3-enyne compounds; when the unsaturated hydrocarbon substrate is a 4-aryl-1,3-enyne compound, the reaction is carried out under ultraviolet light irradiation, and when the unsaturated hydrocarbon substrate is a 4-alkyl-1,3-enyne compound, the reaction is carried out under blue light irradiation.

[0010] This invention provides a method for synthesizing chiral aryl compounds such as chiral diarylalkanes, chiral arylynes, or chiral allenes. The method uses unsaturated hydrocarbons such as alkenes and enynes as raw materials and employs a strategy combining photocatalysis and copper catalysis to expand the substrate scope to enynes. This enables the high-value conversion of low-cost unsaturated hydrocarbons such as alkenes and enynes into chiral aryl compounds. Furthermore, the method features mild reaction conditions, a simple synthetic route, and high efficiency, solving the problems of harsh reaction conditions and limited substrate scope in the synthesis of chiral aryl compounds in existing technologies.

[0011] In this invention, the structure of the oxime ester substrate is as follows:

[0012]

[0013] In this invention, the general structural formula of the arylboronic acid compounds is:

[0014] R 2 -B(OH)2

[0015] R 2 It can be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran.

[0016] In this invention, the general structural formula of the olefin compound is:

[0017]

[0018] R 1 It can be selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene.

[0019] The general structural formula of the 4-aryl-1,3-enyne compounds is:

[0020]

[0021] R 3It can be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 3-thiophene;

[0022] The general structural formula of the 4-alkyl-1,3-enyne compounds is:

[0023]

[0024] R 4 It can be selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, 3-thiophene;

[0025] R 5 It can be selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl.

[0026] In this invention, the chiral aryl compound is a chiral diarylalkane, a chiral arylalkyne, or a chiral allene, and its general structural formula is selected from one of the following:

[0027]

[0028] In the formula, R 1 It may be selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene; R 2 It may be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; R 3 It can be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 3-thiophene; R 4 It can be selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, 3-thiophene; R 5 It can be selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl.

[0029] In this invention, the structural formula of the bisoxazoline ligand is one of the following:

[0030]

[0031] In this invention, the synthesis reaction of the chiral aryl compound is shown in the following reaction:

[0032]

[0033]

[0034] In the formula, R 1 It may be selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene; R 2 It may be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; R 3 It can be selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 3-thiophene; R 4 It can be selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, 3-thiophene; R 5 It can be selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl.

[0035] In this invention, the copper catalyst is cuprous tetraacetonitrile hexafluorophosphate or cuprous tetraacetonitrile trifluoromethanesulfonate.

[0036] In this invention, the mixed solvent includes at least one of toluene, acetonitrile, tetrahydrofuran, and cyclopentyl methyl ether.

[0037] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0038] This invention provides a method for synthesizing chiral aryl compounds such as chiral diarylalkanes, chiral arylynes, or chiral allenes. The method uses unsaturated hydrocarbons such as alkenes and enynes as raw materials and employs a strategy combining photocatalysis and copper catalysis to expand the substrate scope to enynes. This enables the high-value conversion of low-cost unsaturated hydrocarbons such as alkenes and enynes into chiral aryl compounds. Furthermore, the method features mild reaction conditions, a simple synthetic route, and high efficiency, solving the problems of harsh reaction conditions and limited substrate scope in the synthesis of chiral aryl compounds in existing technologies. Detailed Implementation

[0039] The applicant will now provide a detailed description of the method of the present invention with reference to specific embodiments, in order to enable those skilled in the art to clearly understand the present invention. However, the following embodiments should not be construed in any way as limiting the scope of protection claimed in the present invention.

[0040] The method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids of the present invention includes the following steps:

[0041] The copper catalyst and the bisoxazoline ligand were dissolved in a mixed solvent and stirred until homogeneous. Unsaturated hydrocarbon substrates, oxime ester substrates and arylboronic acid compounds were added, and the reaction was carried out at 0°C for 12–32 h.

[0042] The unsaturated hydrocarbon substrate includes one of olefins, 4-aryl-1,3-enyne compounds, or 4-alkyl-1,3-enyne compounds; when the unsaturated hydrocarbon substrate is a 4-aryl-1,3-enyne compound, the reaction is carried out under ultraviolet light irradiation, and when the unsaturated hydrocarbon substrate is a 4-alkyl-1,3-enyne compound, the reaction is carried out under blue light irradiation.

[0043] Examples 1-19 provide a method for synthesizing chiral diaryl alkane compounds.

[0044] Chiral diarylalkane compounds have the structural formula shown in general formula I:

[0045]

[0046] In the formula, R 1 Selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene; R 2 It is selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran.

[0047] Chiral diaryl alkane compounds having the above general formula I can have any of the following structures:

[0048]

[0049] The general formula for the synthesis of chiral diaryl alkane compounds having the above-mentioned general structural formula I is as follows:

[0050]

[0051] In the general formula for synthesis, R 1 R 2 Definition and the general structural formula of chiral diaryl alkane compounds R 1 R 2 The definitions are the same; where Cu(CH3CN)4PF6 is cuprous tetraacetonitrile hexafluorophosphate, toluene is toluene, CH3CN is acetonitrile, ee: enantiomer excess, yield: yield.

[0052] In the general formula for the synthetic reaction, olefin compound IV can have any of the following structures:

[0053]

[0054] In the general formula for the synthetic reaction, arylboronic acid compound VI can have any of the following structures:

[0055]

[0056] The specific synthetic steps for chiral diaryl alkane compounds are as follows:

[0057] In a glove box, cuprous hexafluorophosphate tetraacetonitrile and ligand VII were dissolved in a mixed solvent of toluene and acetonitrile and stirred for 30 minutes. Then, olefin compound IV, oxime ester substrate V and arylboronic acid compound VI were added. After reacting at 0°C for 12-24 h, the target product with general formula I was directly obtained by column chromatography with petroleum ether / ethyl acetate (v:v) = 10:1-5:1.

[0058] Example 1

[0059] Preparation of compound I-1

[0060] Inside a glove box, 1.86 mg of Cu(CH3CN)4PF6 (0.005 mmol, 5.0 mol%) and chiral ligand VII (4.43 mg, 0.006 mmol, 6.0 mol%) were weighed and added to a glass vial, followed by 1.5 mL of toluene and 0.1 mL of acetonitrile. The mixture was stirred in the glove box for 30 min. Then, 0.1 mmol (1.0 eq.) of arylboronic acid compound VI-1, 0.3 mmol (3.0 eq.) of olefin compound IV-1, and 0.2 mmol (2.0 eq.) of oxime ester V were weighed and added to the reaction system (in no particular order). The system was sealed and removed from the glove box. The reaction flask was placed in an incubator (pre-cooled to 0 °C) and stirred. After 12 h, the mixture was removed and monitored. The reaction system was filtered through a filter, washed with dichloromethane, concentrated, and then purified by dry column chromatography with the addition of silica gel powder to obtain compound I-1. (Eluent: petroleum ether / ethyl acetate = 10:1 to 5:1).

[0061] Compound I-1 Prepared from olefin compound IV-1 and arylboronic acid compound VI-1 as substrates, with a yield of 77% and an enantiomeric excess of 93% (determined by chiral HPLC; HPLC analysis was performed using a chiral AD-H column, isopropanol:n-hexane ratio 90:10, v:v), 0.5 mL / min, 210 nm, 25 °C, with a retention time of t. R (minor) = 23.89min,t R(major) = 21.62 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.80-7.69 (m, 4H), 7.48-7.40 (m, 2H), 7.33-7.26 (m, 5H), 7.22-7.15 (m, 1H) ,4.05(t,J=7.8Hz,1H),2.29(t,J=7.2Hz,2H),2.23-2.14(m,2H),1.75-1.67(m,2H),1.49-1.42(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.4,142.0,133.5,132.2,128.5,128.2,127.8,127.7,127.6,126.5,126 .3,126.0,125.8,125.5,119.6,77.3,77.0,76.7,51.1,34.6,27.3,25.5,17.1.HRMS(ESI):m / z[M+Na] + calcdfor C 22 H 21 NNa:322.1566, found:322.1566.

[0062] Example 2

[0063] Preparation of compound I-2

[0064] The preparation steps are the same as in Example 1, except that compound I-2 It was prepared using olefin compound IV-2 and arylboronic acid compound VI-1 as substrates.

[0065] Yield 63%, enantiomeric excess 88% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time: 1 H NMR (400MHz, CDCl3) δ (ppm) 7.31-7.27 (m, 2H), 7.21-7.16 (m, 5H), 7.01-6.93 (m, 2H), 3.87 (t, J=7.8Hz,1H),2.29(t,J=7.1Hz,2H),2.09-2.00(m,2H),1.72-1.64(m,2H),1.44-1.36(m,2H). 13C NMR (100MHz, CDCl3) δ (ppm) 161.4 (d, J = 244.4Hz), 144.3, 140.3 (d, J = 2.7Hz), 129.0 (d, J = 7.8Hz), 128.6,127.6,126.4,119.5,115.3(d,J=21.1Hz),77.3,77.0,76.7,50.3,35.0,27.2,25.4,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-116.9.HRMS(ESI):m / z[M+Na] + calcd forC 18 H 18 FNNa:290.1315,found:290.1312.

[0066] Example 3

[0067] Preparation of compound I-3

[0068] The preparation steps are the same as in Example 1, except that compound I-3 It was prepared using olefin IV-3 and arylboronic acid VI-1 as substrates.

[0069] Yield 65%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time: R (major) = 24.01 min, t R (minor) = 29.06 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.31-7.14 (m, 9H), 3.86 (t, J = 7.8Hz, 1H), 2.30 (t, J = 7.1Hz, 2H), 2.09-2.00 (m, 2H), 1.72-1.65 (m, 2H), 1.44-1.37 (m, 2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.0, 143.1, 132.0, 129.0, 128.6, 127.6, 126.5, 119.6,77.3,77.0,76.7,50.5,34.7,27.1,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 18 H 18 ClNNa:306.1020,found:306.1019.

[0070] Example 4

[0071] Preparation of compound I-4

[0072] The preparation steps are the same as in Example 1, except that compound I-4 It was prepared using olefin IV-4 and arylboronic acid VI-1 as substrates.

[0073] Yield 71%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 26.15 min, t R (minor) = 30.86 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.41-7.38 (m, 2H), 7.30-7.27 (m, 2H), 7.21-7.17 (m, 3H), 7.11-7.08 (m, 2H) ,3.85(t,J=7.8Hz,1H),2.29(t,J=7.2Hz,2H),2.09-1.99(m,2H),1.71-1.64(m,2H),1.44-1.36(m,2H). 13 C NMR(100MHz,CDCl3)δ(ppm)143.9,143.6,131.6,129.4,128.6,127.6,126.5,120 .1,119.5,77.3,77.0,76.7,50.5,34.7,27.1,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 18 H 18 BrNNa:350.0515,found:350.0512.

[0074] Example 5

[0075] Preparation of compound I-5

[0076] The preparation steps are the same as in Example 1, except that compound I-5 It was prepared using olefin IV-5 and arylboronic acid VI-1 as substrates.

[0077] Yield 72%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane ratio 80:20, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time tR (major) = 12.16 min, t R (minor) = 10.99 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.95 (d, J = 8.4Hz, 2H), 7.31-7.26 (m, 4H), 7.22-7.18 (m, 3H), 3.95 (t, J = 7. 8Hz,1H),3.88(s,3H),2.29(t,J=7.1Hz,2H),2.12-2.02(m,2H),1.72-1.65(m,2H),1.45-1.37(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 166.9,149.9,143.6,129.9,128.7,128.3,127.7,127.7,12 6.6,119.5,77.3,77.0,76.7,52.0,51.1,34.6,27.1,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 21 NNaO2:330.1465,found:330.1463.

[0078] Example 6

[0079] Preparation of compound I-6

[0080] The preparation steps are the same as in Example 1, except that compound I-6 It was prepared using olefin IV-6 and arylboronic acid VI-1 as substrates.

[0081] Yield 45%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 21.09 min, t R (minor) = 19.91 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.57 (d, J = 8.3Hz, 2H), 7.34-7.29 (m, 4H), 7.24-7.18 (m, 3H), 3.95 (t ,J=7.8Hz,1H),2.31(t,J=7.1Hz,2H),2.15-2.01(m,2H),1.73-1.66(m,2H),1.45-1.37(m,2H). 13C NMR (100MHz, CDCl3) δ (ppm) 150.2, 142.8, 132.4, 128.8, 128.5, 127.7, 126.9, 119.4, 118.8,110.2,77.3,77.0,76.7,51.2,34.4,27.1,25.3,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 19 H 18 N2Na:297.1362,found:297.1362.

[0082] Example 7

[0083] Preparation of compound I-7

[0084] The preparation steps are the same as in Example 1, except that compound I-7 It was prepared using olefin IV-7 and arylboronic acid VI-1 as substrates.

[0085] Yield 83%, enantiomeric excess 83% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 10.84 min, t R (minor) = 9.58 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.56-7.49 (m, 4H), 7.43-7.39 (m, 2H), 7.33-7.24 (m, 7H), 7.21-7.17 (m, 1H) ,3.93(t,J=7.8Hz,1H),2.29(t,J=7.2Hz,2H),2.13-2.07(m,2H),1.73-1.65(m,2H),1.48-1.40(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.4,143.7,140.8,139.1,128.7,128.6,128.1,127.7,127.2,127 .1,126.9,126.3,119.6,77.3,77.0,76.7,50.8,34.8,27.2,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 24 H 23 NNa:348.1723, found:348.1723.

[0086] Example 8

[0087] Preparation of compound I-8

[0088] The preparation steps are the same as in Example 1, except that compound I-8 It was prepared using olefin IV-8 and arylboronic acid VI-1 as substrates.

[0089] Yield 76%, enantiomeric excess 84% ​​(determined by chiral HPLC; HPLC analysis using a chiral AZ-H column, isopropanol:n-hexane 95:5, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 15.17 min, t R (minor) = 14.33 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.34-7.20 (m, 6H), 6.87 (d, J = 7.6Hz, 1H), 6.82-6.75 (m, 2H), 3.89 (t, J = 7. 8Hz,1H),3.81(s,3H),2.33(t,J=7.2Hz,2H),2.13-2.07(m,2H),1.76-1.69(m,2H),1.50-1.42(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 159.7,146.2,144.4,129.5,128.5,127.7,126.3,120.2,11 4.0,111.1,77.3,77.0,76.7,55.1,51.1,34.8,27.2,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 19 H 21 NNaO: 302.1515, found: 302.1514.

[0090] Example 9

[0091] Preparation of compound I-9

[0092] The preparation steps are the same as in Example 1, except that compound I-9 It was prepared using olefin IV-9 and arylboronic acid VI-1 as substrates.

[0093] Yield 67%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis using a chiral IC column, isopropanol:n-hexane 95:5, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time tR (major) = 21.24 min, t R (minor) = 22.79 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.32-7.28 (m, 2H), 7.23-7.14 (m, 6H), 7.12-7.10 (m, 1H), 3.86 (t, J=7.8Hz,1H),2.30(t,J=7.2Hz,2H),2.09-2.03(m,2H),1.73-1.65(m,2H),1.45-1.37(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 146.7,143.7,134.3,129.8,128.7,127.8,127.7,126.6,126 .5,125.9,119.5,77.3,77.0,76.7,50.8,34.7,27.1,25.4,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 18 H 18 ClNNa:306.1020,found:306.1016.

[0094] Example 10

[0095] Preparation of compound I-10

[0096] The preparation steps are the same as in Example 1, except that compound I-10 It was prepared using olefin IV-10 and arylboronic acid VI-1 as substrates.

[0097] Yield 53%, enantiomeric excess 84% ​​(determined by chiral HPLC; HPLC analysis using a chiral IC column, isopropanol:n-hexane 95:5, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 24.27 min, t R (minor) = 26.24 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.31-7.27 (m, 2H), 7.25-7.18 (m, 4H), 6.98 (d, J = 3.1Hz, 1H), 6.90 (dd, J = 5.0, 1.3H z,1H),3.95(t,J=7.7Hz,1H),2.28(t,J=7.2Hz,2H),2.14-1.95(m,2H),1.72-1.61(m,2H),1.49-1.31(m,2H).13 C NMR (100MHz, CDCl3) δ (ppm) 145.6,144.1,128.5,127.7,127.5,126.4,125.6,120 .1,119.6,77.3,77.0,76.7,46.7,35.3,27.1,25.3,17.0.HRMS(ESI):m / z[M+Na] + calcd for C 16 H 17 NNaS:278.0974, found:278.0971.

[0098] Example 11

[0099] Preparation of compound I-11

[0100] The preparation steps are the same as in Example 1, except that compound I-11 It was prepared using olefin IV-11 and arylboronic acid VI-1 as substrates.

[0101] Yield 80%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 25.75 min, t R (minor) = 22.68 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.58 (d, J = 2.2Hz, 1H), 7.45 (d, J = 1.9Hz, 1H), 7.40 (d, J = 8.5Hz, 1H), 7.30-7.24 (m, 4H), 7.20-7.14 (m, 2H) ,6.71(dd,J=2.2,1.0Hz,1H),3.99(t,J=7.8Hz,1H),2.29(t,J=7.2Hz,2H),2.15-2.09(m,2H),1.73-1.66(m,2H),1.47-1.39(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.7,140.8,139.9,137.7,128.5,127.7,126.7,126.3,124.6,123 .8,122.5,122.3,119.6,77.3,77.0,76.7,50.9,35.0,27.3,25.4,17.1.HRMS(ESI):m / z[M+Na] + calcd for C20 H 19 NNaS:328.1130, found:328.1129.

[0102] Example 12

[0103] Preparation of compound I-12

[0104] The preparation steps are the same as in Example 1, except that compound I-12 It was prepared using olefin IV-12 and arylboronic acid VI-1 as substrates.

[0105] Yield 72%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 31.97 min, t R (minor) = 30.31 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.58 (d, J = 2.2Hz, 1H), 7.45 (d, J = 1.9Hz, 1H), 7.40 (d, J = 8.5Hz, 1H), 7.30-7.23 (m, 4H), 7.20-7.14 (m, 2H) ,6.71(dd,J=2.2,1.0Hz,1H),3.99(t,J=7.8Hz,1H),2.29(t,J=7.2Hz,2H),2.15-2.09(m,2H),1.73-1.66(m,2H),1.47-1.39(m,2H). 13 C NMR(100MHz,CDCl3)δ(ppm)1 153.6,145.3,145.0,139.2,128.5,127.7,127.5,126.2,124.3,119.8,119.7,11 1.3,106.5,77.3,77.0,76.7,50.9,35.2,27.3,25.4,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 16 H 17 NNaO: 312.1359, found: 312.1363.

[0106] Example 13

[0107] Preparation of compound I-13

[0108] The preparation steps are the same as in Example 1, except that compound I-13 It was prepared using olefin IV-13 and arylboronic acid VI-1 as substrates.

[0109] Yield 64%, enantiomeric excess 91% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 28.99 min, t R (minor) = 27.03 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.93 (s, 1H), 7.67-7.63 (m, 3H), 7.52 (dd, J = 8.8, 1.9Hz, 1H), 7.35-7.14 (m, 7H) ),4.03(t,J=7.8Hz,1H),2.29(t,J=7.1Hz,2H),2.20-2.11(m,2H),1.74-1.67(m,2H),1.48-1.40(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.0,142.6,133.2,131.9,129.6,129.4,129.3,128.6,127.8,127.5,127 .3,126.5,125.7,119.6,119.3,77.3,77.0,76.7,51.1,34.5,27.2,25.4,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 22 H 20 BrNNa:400.0671,found:400.0669.

[0110] Example 14

[0111] Preparation of compound I-14

[0112] The preparation steps are the same as in Example 1, except that compound I-14 It was prepared using olefin IV-14 and arylboronic acid VI-1 as substrates.

[0113] Yield 75%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane ratio 80:20, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.75 min, t R (minor) = 10.36 min. 1H NMR (400MHz, CDCl3) δ (ppm) 8.60 (dd, J = 12.0, 8.4Hz, 2H), 7.86 (d, J = 7.8Hz, 1H), 7.74-7.68 (m, 3H), 7.64-7.49 (m, 3H), 7.30 (d, J = 4 .3Hz,4H),7.22-7.17(m,1H),4.10(t,J=7.8Hz,1H),2.27(t,J=7.1Hz,2H),2.24-2.14(m,2H),1.74-1.67m,2H),1.53-1.42(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 144.4,142.9,132.1,131.8,130.1,128.7,128.6,128.5,127.8,127.1,126.9,126.8,126 .8,126.5,126.4,126.3,123.0,122.5,119.6,77.3,77.0,76.7,50.9,34.8,27.3,25.4,17.0.HRMS(ESI):m / z[M+Na] + calcdfor C 26 H 23 NNa: 372.1723, found: 372.1725.

[0114] Example 15

[0115] Preparation of compound I-15

[0116] The preparation steps are the same as in Example 1, except that compound I-15 It was prepared using olefin IV-1 and arylboronic acid VI-2 as substrates.

[0117] Yield 81%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.63 min, t R (minor) = 11.45 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.81-7.74 (m, 3H), 7.66 (s, 1H), 7.50-7.41 (m, 2H), 7.29-7.20 (m, 3H), 6.98 (d, J = 8. 7Hz,2H),4.03(t,J=7.8Hz,1H),2.28(t,J=7.2Hz,2H),2.22-2.06(m,2H),1.74-1.66(m,2H),1.49-1.39(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 161.4 (d, J = 244.6Hz), 141.7, 140.1 (d, J = 3.2Hz), 133.4, 132.2, 129.2, 129.1, 128.3, 127.6 (d,J=8.0Hz),126.3,126.1,125.7,125.6,119.6,115.3(d,J=21.2Hz),77.3,77.0,76.7,50.3,34.7,27.2,25.4,17.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-116.8.HRMS(ESI):m / z[M+Na] + calcd for C 22 H 20 FNNa:340.1472,found:340.1474.

[0118] Example 16

[0119] Preparation of compound I-18

[0120] The preparation steps are the same as in Example 1, except that compound I-18 Prepared from olefin IV-1 and arylboronic acid VI-5 as substrates, the reaction was extended to 24 h.

[0121] Yield 79%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis using a chiral AZ column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 220 nm, 25 °C, retention time t R (major) = 44.13 min, t R (minor) = 47.35 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.82-7.73 (m, 4H), 7.56-7.29 (m, 12H), 4.10 (t, J = 7.7Hz, 1H), 2.30 (t, J = 7.2Hz, 2H), 2.26-2.16 (m, 2H), 1.77-1.69 (m, 2H), 1.53-1.42 (m, 2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 143.5,141.8,140.8,139.2,133.5,132.2,128.7,128.3,128.2,127.7,127.6,127.3,127 .1,127.0,126.5,126.1,125.8,125.5,119.6,77.3,77.0,76.7,50.8,34.6,27.3,25.5,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 28 H 25 NNa:398.1879, found:398.1872.

[0122] Example 17

[0123] Preparation of compound I-19

[0124] The preparation steps are the same as in Example 1, except that compound I-19 The catalyst was prepared using olefin IV-1 and arylboronic acid VI-6 as substrates, with the amount of catalyst doubled, specifically Cu(CH3CN)4PF6 (3.72 mg, 0.01 mmol, 10 mol%) and chiral ligand VII (8.86 mg, 0.012 mmol, 12 mol%), and the reaction was extended to 24 h.

[0125] Yield 60%, enantiomeric excess 86% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane ratio 80:20, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 11.53 min, t R (minor) = 10.13 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.80-7.72 (m, 3H), 7.67 (s, 1H), 7.47-7.39 (m, 2H), 7.31-7.29 (m, 1H), 7.18 (d, J = 8.7Hz, 2H), 6.82 (d, J=8.7Hz,2H),4.00(t,J=7.8Hz,1H),3.76(s,3H),2.28(t,J=7.2Hz,2H),2.20-2.06(m,2H),1.74-1.66(m,2H),1.48-1.40(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 158.0,142.4,136.5,133.5,132.1,128.7,128.2,127.6,127.5,126.5,126.0 ,125.6,125.4,119.6,113.9,77.3,77.0,76.7,55.2,50.2,34.8,27.3,25.5,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 23 H 23 NNaO: 356.1672, found: 356.1679.

[0126] Example 18

[0127] Preparation of compound I-20

[0128] The preparation steps are the same as in Example 1, except that compound I-20 It was prepared using olefin IV-1 and arylboronic acid VI-7 as substrates.

[0129] Yield 81%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 80:20, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 18.82 min, t R (minor) = 22.34 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.81-7.75 (m, 3H), 7.68 (s, 1H), 7.49-7.41 (m, 2H), 7.31-7.21 (m, 3H), 7.06 (d, J = 7.7Hz, 1H), 6.97 (dt, J = 10.2, 2.1H z,1H),6.88(td,J=8.4,7.9,2.6Hz,1H),4.05(t,J=7.8Hz,1H),2.29(t, J=7.2Hz,2H),2.23-2.09(m,2H),1.75-1.67(m,2H),1.49-1.41(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 163.0 (d, J = 245.8Hz), 147.1 (d, J = 6.9Hz), 141.2, 133.4, 132.2, 130.0, 129.9, 128.4, 127.7, 127.6, 126.2 (d, J = 5.1 Hz),125.9,125.7,123.5(d,J=2.7Hz),119.6,114.6(d,J=21.5Hz),113 .2(d,J=21.1Hz),77.3,77.0,76.7,50.8,50.8,34.5,27.2,25.4,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-113.0.HRMS(ESI):m / z[M+Na] + calcd for C 22 H 20 FNNa:340.1472,found:340.1465.

[0130] Example 19

[0131] Preparation of compound I-22

[0132] The preparation steps are the same as in Example 1, except that compound I-22 The catalyst was prepared by doubling the amount of olefin IV-1 and arylboronic acid VI-9 as substrates, specifically Cu(CH3CN)4PF6 (3.72 mg, 0.01 mmol, 10 mol%) and chiral ligand VII (8.86 mg, 0.012 mmol, 12 mol%), and the reaction was extended to 24 h.

[0133] Yield 72%, enantiomeric excess 88% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time tR (major) = 14.28 min, t R (minor) = 13.25 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.81-7.76 (m, 4H), 7.54 (s, 1H), 7.49-7.42 (m, 3H), 7.38-7.36 (m, 1H), 7.30 (d, J = 7.9Hz, 1H), 7.24-7. 20(m,1H),7.09-7.05(m,1H),4.20(t,J=6.5Hz,1H),2.33-2.24(m,3H),2.17-2.08(m,1H),1.79-1.64(m,2H),1.53-1.40(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 155.5,141.1,140.2,133.4,132.4,128.4,127.7,127.6,127.4,126.3,126.1,126.0,125 .6,124.3,123.7,122.3,120.2,119.6,111.4,77.3,77.0,76.7,41.9,34.3,27.0,25.4,17.1.HRMS(ESI):m / z[M+Na] + calcd forC 20 H 19 NNaO: 362.1515, found: 362.1514.

[0134] Examples 20-38 provide a method for synthesizing chiral arylkyne compounds.

[0135] Chiral aryl alkynes have the structural formula shown in general formula II:

[0136]

[0137] In the formula, R 2 Selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; R 3 It is selected from one of 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, and 3-thiophene.

[0138] Chiral aryl alkynes having the above general formula II can have any of the following structures:

[0139]

[0140] The general formula for the synthesis of chiral arylalynyl compounds having the above-mentioned general structural formula II is as follows:

[0141]

[0142] In the general formula for synthesis, R 2 R 3 Definition and the general structural formula of chiral aryl alkynes R 2 R 3 The definitions are the same; where Cu(CH3CN)4OTf is copper tetraacetonitrile trifluoromethanesulfonate, toluene is toluene, THF is tetrahydrofuran, ee: enantiomer excess, yield: yield.

[0143] In the general formula for the synthesis reaction, the structure of arylboronic acid compound VI is the same as that in Examples 1-19, and the structure of 4-aryl-1,3-enyne compound VIII can be any of the following structures:

[0144]

[0145] The specific synthetic steps for chiral aryl alkynes are as follows:

[0146] In a glove box, cuprous trifluoromethanesulfonate tetraacetonitrile and ligand IX were dissolved in a mixed solvent of toluene and tetrahydrofuran and stirred for 30 minutes. Subsequently, 4-aryl-1,3-enyne compound VIII, oxime ester substrate V, and arylboronic acid compound VI were added. After reacting under ultraviolet light at 0°C for 24 h, the target product with general formula II was directly obtained by column chromatography with petroleum ether / ethyl acetate (v:v) = 20:1–10:1.

[0147] Example 20

[0148] Preparation of compound II-1

[0149] Inside a glove box, copper salt Cu(CH3CN)4OTf (1.88 mg, 0.0050 mmol, 5.0 mol%) and chiral ligand IX (6.09 mg, 0.010 mmol, 10.0 mol%) were weighed and added to a glass vial, followed by 1.3 mL of tetrahydrofuran and 0.2 mL of toluene. The vial was then capped and stirred in the glove box for 30 minutes (resulting in a colorless, clear solution). Subsequently, arylboronic acid compound VI-1 (0.1 mmol, 1.0 eq.), 4-aryl-1,3-enyne compound VIII-1 (0.3 mmol, 3.0 eq.), and oxime ester substrate V (0.2 mmol, 2.0 eq.) were weighed and added to the reaction flask. The flask was sealed and removed from the glove box. The reaction flask was then transferred to a pre-cooled incubator and stirred under 20 W 390 nm Kessil LEDs illumination for 24 h. The reaction was then removed and monitored. After filtration through a filter head, the reaction system was washed with dichloromethane, concentrated, and an appropriate amount of silica gel powder was added. The target product II-1 was then separated by dry column chromatography (eluent: petroleum ether / ethyl acetate = 20:1 to 10:1).

[0150] Compound II-1 It was prepared using olefin VIII-1 and arylboronic acid VI-1 as substrates.

[0151] Yield 78%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 14.28 min, t R (minor) = 13.25 min.t R (major) = 17.26 min, t R (minor) = 14.29 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.47-7.41 (m, 4H), 7.39-7.24 (m, 7H), 3.87 (t, J = 7.1Hz, 1H), 2.35 (t, J = 6.9Hz, 2H), 1.89-1.76 (m, 2H), 1.76-1.59 (m, 4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 141.6,131.6,128.6,128.3,128.2,127.9,127.4,126.9,123.5 ,119.6,90.7,83.7,77.3,77.0,76.7,38.1,37.7,26.5,25.2,17.1.HRMS(ESI):m / z[M+Na]+ calcd for C 20 H 19 NNa:296.1410, found:296.1413.

[0152] Example 21

[0153] Preparation of compound II-2

[0154] The preparation steps are the same as in Example 20, except that compound II-2 It was prepared using enyne VIII-1 and arylboronic acid VI-2 as substrates.

[0155] Yield 84%, enantiomeric excess 88% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.50 min, t R (minor) = 10.59 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.45-7.43 (m, 2H), 7.39-7.36 (m, 2H), 7.33-7.29 (m, 3H), 7.06-7. 00(m,2H),3.86(t,J=7.1Hz,1H),2.36(t,J=6.8Hz,2H),1.86-1.79(m,2H),1.76-1.61(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 161.7 (d, J = 245.1Hz), 137.3 (d, J = 3.3Hz), 131.6, 128.8 (d, J = 8.0Hz), 128.3 ,128.0,123.2,119.6,115.4(d,J=21.4Hz).90.4,83.9,77.3,77.0,76.7,37.7,37.4,26.5,25.1,17.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-116.0.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 18 FNNa:314.1315,found:314.1317.

[0156] Example 22

[0157] Preparation of compound II-3

[0158] The preparation steps are the same as in Example 20, except that compound II-3 It was prepared using enyne VIII-1 and arylboronic acid VI-3 as substrates.

[0159] Yield 81%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 17.41 min, t R (minor) = 10.34 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.46-7.43 (m, 2H), 7.36-7.30 (m, 7H), 3.85 (t, J = 7.1Hz, 1H), 2.36 (t, J = 6.8Hz, 2H), 1.86-1.81 (m, 2H), 1.76-1.59 (m, 4H). 13 CNMR(100MHz,CDCl3)δ(ppm)140.1,132.6,131.6,128.7,128.7,128.3,128.1,123.2 ,119.5,90.1,84.0,77.3,77.0,76.7,37.6,26.4,25.1,17.1.HRMS(ESI):m / z[M+Na] + calcd forC 20 H 18 ClNNa:330.120,found:330.123.

[0160] Example 23

[0161] Preparation of compound II-4

[0162] The preparation steps are the same as in Example 20, except that compound II-4 It was prepared using enyne VIII-1 and arylboronic acid VI-4 as substrates.

[0163] Yield 76%, enantiomeric excess 85% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 21.95 min, t R (minor) = 12.35 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.49-7.43 (m, 4H), 7.33-7.28 (m, 5H), 3.83 (t, J = 7.1Hz, 1H), 2.37 (d, J = 6.8Hz, 2H), 1.86-179 (m, 2H), 1.75-1.60 (m, 4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 140.6,131.7,131.6,129.1,128.3,128.1,123.2,120.7,11 9.5,90.0,84.1,77.3,77.0,76.7,37.7,37.5,26.4,25.1,17.1.HRMS(ESI):m / z[M+Na] + calcdfor C 20 H 18 BrNNa:374.0515,found:374.0513.

[0164] Example 24

[0165] Preparation of compound II-5

[0166] The preparation steps are the same as in Example 20, except that compound II-5 It was prepared using enyne VIII-1 and arylboronic acid VI-5 as substrates.

[0167] Yield 73%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 30.45 min, t R (minor) = 18.91 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.61-7.57 (m, 4H), 7.50-7.42 (m, 6H), 7.37-7.30 (m, 4H) ,3.92(t,J=7.1Hz,1H),2.37(t,J=6.7Hz,2H),1.93-1.88(m,2H),1.77-1.65(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 140.8, 140.7, 139.9, 131.6, 128.8, 128.3, 127.9, 127.8, 127.3, 127.2, 12 7.1,123.4,119.6,90.6,83.8,77.3,77.0,76.7,37.8,37.6,26.6,25.2,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 26 H 23 NNa: 372.1723, found: 372.1725.

[0168] Example 25

[0169] Preparation of compound II-6

[0170] The preparation steps are the same as in Example 20, except that compound II-6 It was prepared using enyne VIII-1 and arylboronic acid VI-6 as substrates.

[0171] Yield 75%, enantiomeric excess 85% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 26.02 min, t R (minor) = 15.07 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.47-7.42 (m, 2H), 7.31-7.29 (m, 5H), 7.16 (d, J = 7.8Hz, 2H),3.83(t,J=7.1Hz,1H),2.36-2.33(m,5H),1.88-1.81(m,2H),1.75-1.59(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 138.6, 136.5, 131.6, 129.3, 128.2, 127.8, 127.2, 123.5, 119. 6,91.0,83.5,77.3,77.0,76.7,37.7,37.7,26.5,25.2,21.0,17.1.HRMS(ESI):m / z[M+Na] + calcd for C 21 H 21 NNaO: 326.1515, found: 326.1518.

[0172] Example 26

[0173] Preparation of compound II-7

[0174] The preparation steps are the same as in Example 20, except that compound II-7 It was prepared using enyne VIII-1 and arylboronic acid VI-7 as substrates.

[0175] Yield 67%, enantiomeric excess 85% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 220 nm, 25 °C, retention time t R (major) = 16.05 min, t R (minor) = 11.21 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.47-7.43 (m, 2H), 7.34-7.28 (m, 4H), 7.19-7.14 (m, 2H), 6.98-6. 93(m,1H),3.88(t,J=7.1Hz,1H),2.36(t,J=6.8Hz,2H),1.88-1.83(m,2H),1.77-1.63(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 162.3 (d, J = 246.1Hz), 144.2 (d, J = 7.0Hz), 131.7, 130.1 (d, J = 8.4Hz), 128.3, 128.1, 123.2, 123.1 (d, J = 2.9Hz), 119.6, 114.4 (d, J = 22.0Hz), 113.4 (d, J = 21.2Hz), 89.9, 84.1, 77.4, 77.0, 76.7, 37.9 (d, J = 1.8Hz), 37.5, 26.5, 25.2, 17.2. 19 F NMR(376MHz, CDCl3)δ(ppm)-112.9.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 18 FNNa:314.1315,found:314.1312.

[0176] Example 27

[0177] Preparation of compound II-8

[0178] The preparation steps are the same as in Example 20, except that compound II-8 It was prepared using enyne VIII-1 and arylboronic acid VI-8 as substrates.

[0179] Yield 64%, enantiomeric excess 83% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 17.50 min, t R (minor) = 11.83 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.57 (t, J = 1.9 Hz, 1H), 7.47-7.43 (m, 2H), 7.41-7.39 (m, 1H), 7.35-7.31 (m, 4H) ,7.22(t,J=7.8Hz,1H),3.84(t,J=7.1Hz,1H),2.37(t,J=2.8Hz,2H),1.87-1.82(m,2H),1.77-1.62(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 143.9,131.7,130.5,130.2,130.1,128.3,128.1,126.1,123.2,12 2.7,119.6,89.7,84.3,77.4,77.0,76.7,37.9,37.6,26.5,25.2,17.2.HRMS(ESI):m / z[M+Na] + calcd forC 20 H 18 BrNNa:374.0515,found:374.0519.

[0180] Example 28

[0181] Preparation of compound II-9

[0182] The preparation steps are the same as in Example 20, except that compound II-9 It was prepared using enyne VIII-1 and arylboronic acid VI-9 as substrates.

[0183] Yield 84%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 22.42 min, t R (minor) = 17.63 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.73-7.71 (m, 2H), 7.63 (s, 1H), 7.51-7.43 (m, 3H), 7.34-7.25 (m, 5H), 7.22 (t,J=7.8Hz,1H),4.08(t,J=5.9Hz,1H),2.37(t,J=5.4Hz,2H),2.05-1.98(m,2H),1.78-1.702(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 155.7,141.8,131.6,128.3,128.1,126.5,124.4,123.2,122.5,120.5,11 9.9,119.5,111.8,89.3,82.9,77.3,77.0,76.7,34.6,28.3,26.4,25.1,17.1.HRMS(ESI):m / z[M+Na] + calcd forC 22 H 19 NNaO: 336.1359, found: 336.1364.

[0184] Example 29

[0185] Preparation of compound II-10

[0186] The preparation steps are the same as in Example 20, except that compound II-10 It was prepared using enyne VIII-2 and arylboronic acid VI-2 as substrates.

[0187] Yield 79%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 8.86 min, t R (minor) = 9.81 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.59 (td, J = 7.6, 1.8 Hz, 1H), 7.46-7.41 (m, 2H), 7.28-7.23 (m, 1H), 7.16 (td, J = 7.5, 1 .3Hz,1H),7.07-6.98(m,3H),4.21(t,J=7.1Hz,1H),2.37(t,J=6.6Hz,2H),1.88-1.82(m,2H),1.77-1.64(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 162.4 (d, J = 242.6Hz), 159.9 (d, J = 239.0Hz), 133.5 (d, J=8.3Hz),129.2(d,J=4.0Hz),128.6(d,J=8.2Hz),128.4(d,J=14.2Hz),124.4(d,J =3.5Hz),119.5,119.3(d,J=3.2Hz),115.6(d,J=21.9Hz),115.3(d,J=21.9Hz),89 .3(d,J=1.5Hz),82.5,77.3,77.0,76.7,36.0,31.3(d,J=3.4Hz),26.4,25.0,17.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-111.4,-119.5.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 17 F2NNa:332.1221,found:332.1214.

[0188] Example 30

[0189] Preparation of compound II-11

[0190] The preparation steps are the same as in Example 20, except that compound II-11 It was prepared using enyne VIII-3 and arylboronic acid VI-2 as substrates.

[0191] Yield 80%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 10.01 min, t R (minor) = 11.22 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.58 (td, J = 7.6, 1.9 Hz, 1H) 7.40-7.37 (m, 2H), 7.29-7.23 (m, 3H), 7.16 (td, J = 7.3, 1. 2Hz,1H),7.07-7.02(m,1H),4.21(t,J=7.1Hz,1H),2.37(t,J=6.6Hz,2H),1.88-1.83(m,2H),1.77-1.60(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 160.0 (d, J = 246.0Hz), 134.0, 132.9, 129.2 (d, J = 4.0Hz), 128.7 (d, J = 8.3Hz), 128.6, 128.3 (d, J = 14.0Hz), 124.4(d,J=3.5Hz),121.8,119.6,115.4(d,J=21.9Hz),90.7,82.4,77.4,77.2,77.0,76.7,36.0,31.3(d,J=3.3Hz),26.4,25.0,17.1. 19 FNMR(376MHz,CDCl3)δ(ppm)-119.5.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 17 ClFNNa:348.0926,found:348.0919.

[0192] Example 31

[0193] Preparation of compound II-12

[0194] The preparation steps are the same as in Example 20, except that compound II-12 It was prepared using enyne VIII-4 and arylboronic acid VI-2 as substrates.

[0195] Yield 80%, enantiomeric excess 87% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 210 nm, 25 °C, retention time t R (major) = 10.64 min, t R (minor) = 11.74 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.57 (td, J = 7.7, 1.8 Hz, 1H),, 7.46-7.43 (m, 2H), 7.33-7.23 (m, 3H), 7.16 (td, J = 7.5, 1 .3Hz,1H),7.07-7.02(m,1H),4.21(t,J=7.0Hz,1H),2.37(t,J=6.8Hz,2H),1.88-1.83(m,2H),1.79-1.63(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 160.0 (d, J = 245.8Hz), 133.2, 131.5, 129.2 (d, J = 4.0Hz), 128.7 (d, J = 8.1Hz), 128.2 (d, J = 14.2Hz), 1 24.4(d,J=3.6Hz),122.2,119.6,115.4(d,J=22.0Hz),91.0,82.5,77.4,77.0,76.7,36.0,31.3(d,J=3.3Hz),26.4,25.0,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-119.5.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 17 BrFNNa:392.0421,found:392.0425.

[0196] Example 32

[0197] Preparation of compound II-13

[0198] The preparation steps are the same as in Example 20, except that compound II-13 It was prepared using enyne VIII-5 and arylboronic acid VI-2 as substrates.

[0199] Yield 86%, enantiomeric excess 87% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 18.23 min, t R (minor) = 20.48 min. 1 H NMR(400MHz, CDCl3)δ(ppm)7.99-7.97(m,2H),7.59(td,J=7.7,1.8Hz,1H),7.53-7.50(m,2H),7.29-7.24(m,1H),7.17(td,J=7.5 ,1.3Hz,1H),7.08-7.03(m,1H),4.25(t,J=7.0Hz,1H),3.92(s,1H),2.37(t,J=6.8Hz,2H),1.90-1.85(m,2H),1.80-1.63(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 166.6, 159.9 (d, J = 246.0Hz), 131.6, 129.4, 129.3, 129.1 (d, J = 3.9Hz), 128.7 (d, J = 8.3Hz), 128.0, 128.0 (d, J =14.0Hz), 124.4 (d, J = 3.6Hz), 119.5, 115.4 (d, J = 21.9Hz), 93.0, 82.8, 77.3, 77.0, 76.7, 52.2, 35.9, 31.4 (d, J = 3.4Hz), 26.4, 25.0, 17.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-119.4.HRMS(ESI):m / z[M+Na] + calcd for C 22 H 20 FNNaO2:372.1370,found:372.1377.

[0200] Example 33

[0201] Preparation of compound II-14

[0202] The preparation steps are the same as in Example 20, except that compound II-14 It was prepared using enyne VIII-6 and arylboronic acid VI-2 as substrates.

[0203] Yield 87%, enantiomeric excess 86% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.17 min, t R (minor) = 18.86 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.66-7.51 (m, 7H), 7.47-7.43 (m, 2H), 7.38-7.34 (m, 1H), 7.28-7.23 (m, 1H), 7.17 (td, J=7 .5,1.3Hz,1H),7.08-7.03(m,1H),4.26(t,J=6.2Hz,1H),2.37(t,J=6.6Hz,2H),1.90-1.81(m,2H),1.79-1.62(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 160.0 (d, J = 245.9Hz), 140.8, 140.4, 132.1, 129.3 (d, J = 4.0Hz), 128.8, 128.6 (d, J = 8.4Hz), 128.4, 127.6, 127.0 ( d,J=3.3Hz),124.4(d,J=3.5Hz),122.2,119.6,115.3(d,J=22.1Hz),90.3,83.4,77.3,77.0,76.7,36.1,31.3(d,J=3.3Hz),26.4,25.0,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-119.5.HRMS(ESI):m / z[M+Na] + calcd for C 26 H 22 FNNa:390.1628,found:390.1628.

[0204] Example 34

[0205] Preparation of compound II-15

[0206] The preparation steps are the same as in Example 20, except that compound II-15 It was prepared using enyne VIII-7 and arylboronic acid VI-2 as substrates.

[0207] Yield 71%, enantiomeric excess 87% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 6.37 min, t R (minor) = 7.82 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.39-7.32 (m, 6H), 7.05-7.00 (m, 2H), 3.85 (t, J = 7.0Hz, 1H), 2.35 (t, J = 6.8Hz, 2H), 1.85-1.80 (m, 2H), 1.76-1.61 (m, 4H). 13C NMR (100MHz, CDCl3) δ (ppm) 161.9 (d, J = 208.5Hz), 151.3, 137.4 (d, J = 3.9Hz), 131.3, 128.9 (d, J = 8.0Hz), 125. 3,120.2,119.6,115.3(d,J=21.2Hz),89.7,84.0,77.3,77.0,76.7,37.8,37.4,34.7,31.2,26.5,25.1,17.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-116.2.HRMS(ESI):m / z[M+Na] + calcd for C 24 H 26 FNNa:370.1941,found:370.1931.

[0208] Example 35

[0209] Preparation of compound II-16

[0210] The preparation steps are the same as in Example 20, except that compound II-16 It was prepared using enyne VIII-8 and arylboronic acid VI-2 as substrates.

[0211] Yield 73%, enantiomeric excess 89% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.84 min, t R (minor) = 14.39 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.71 (td, J=7.7, 1.9Hz, 1H), 7.59 (dd, J=8.0, 1.3Hz, 1H), 7.48 (dd, J=7.7, 1.7Hz, 1H), 7.1 7(td,J=7.6,1.6Hz,1H),7.05(m,1H),4.30(t,J=6,1Hz,1H),2.38-2.34(m,2H),1.92-1.86(m,2H),1.78-1.68(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 160.0 (d, J = 245.8Hz), 133.4, 132.4, 129.5 (d, J = 3.9Hz), 129.2, 128.6 (d, J = 8.1Hz), 128.1 (d, J = 14.1Hz), 127. 0,125.6,125.3,124.3(d,J=3.5Hz),119.6,115.3(d,J=21.9Hz),94.5,82.3,77.3,77.0,76.7,36.0,31.5(d,J=3.3Hz),26.4,25.1,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-119.6.HRMS(ESI):m / z[M+Na] + calcd forC 20 H 17 BrFNNa:392.0421,found:392.0420.

[0212] Example 36

[0213] Preparation of compound II-17

[0214] The preparation steps are the same as in Example 20, except that compound II-17 It was prepared using enyne VIII-9 and arylboronic acid VI-2 as substrates.

[0215] Yield 67%, enantiomeric excess 94% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 21.03 min, t R (minor) = 19.05 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.43-7.22 (m, 5H), 7.25-7.22 (m, 1H), 7.08-7.01 (m, 2H) ,3.84(t,J=7.1Hz,1H),2.36(t,J=6.8Hz,1H),1.87-1.81(m,2H),1.76-1.60(m,4H). 13C NMR (100MHz, CDCl3) δ (ppm) 161.8 (d, J = 245.3Hz), 136.9 (d, J = 3.3Hz), 134.1, 131.5, 129.8, 129.5, 128.8 (d, J = 8.1Hz), 128.3, 124.9, 119.5, 115.5 (d, J = 21.5Hz), 91.8, 82.5, 77.3, 77.0, 76.7, 37.6, 37.4, 26.4, 25.1, 17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.8.HRMS(ESI):m / z[M+Na] + calcd for C 20 H 17 ClFNNa:348.0926,found:348.0931.

[0216] Example 37

[0217] Preparation of compound II-18

[0218] The preparation steps are the same as in Example 20, except that compound II-18 It was prepared using enyne VIII-10 and arylboronic acid VI-2 as substrates.

[0219] Yield 63%, enantiomeric excess 84% ​​(determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.33 min, t R (minor) = 9.70 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.40-7.35 (m, 2H), 7.27-7.18 (m, 2H), 7.12 (d, J = 7.0Hz, 1H), 7.06-7.01 (m ,2H),3.85(t,J=7.1Hz,1H),2.36(t,J=6.9Hz,2H),2.33(s,3H),1.86-1.80(m,1H),1.76-1.61(m,1H). 13C NMR (100MHz, CDCl3) δ (ppm) 161.7 (d, J = 245.0Hz), 138.0, 137.3 (d, J = 3.3Hz), 132.2, 128.9, 128.8 (d, J = 8.0Hz), 1 28.7,128.2,123.0,119.6,115.4(d,J=21.5Hz),90.0,84.1,77.3,77.0,76.7,37.8,37.4,26.5,25.2,21.2,17.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-116.1.HRMS(ESI):m / z[M+Na] + calcd forC 21 H 20 FNNa:328.1472,found:328.1471.

[0220] Example 38

[0221] Preparation of compound II-19

[0222] The preparation steps are the same as in Example 20, except that compound II-19 It was prepared using enyne VIII-11 and arylboronic acid VI-2 as substrates.

[0223] Yield 73%, enantiomeric excess 88% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 1.0 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.80 min, t R (minor) = 14.04 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.60 (td, J = 7.6, 1.8Hz, 1H), 7.44 (dd, J = 3.0, 1.2Hz, 1H), 7.28-7.22 (m, 1H), 7.17-7. 12(m,1H),7.07-7.02(m,1H),4.21(t,J=7.6Hz,1H),2.36(t,J=6.8Hz,2H),1.87-1.81(m,1H),1.78-1.62(m,1H). 13C NMR (100MHz, CDCl3) δ (ppm) 159.9 (d, J = 246.0Hz), 130.0, 129.2 (d, J = 4.1Hz), 128.6 (d, J = 8.3Hz), 128.4 (d, J = 13.8Hz), 128.3, 125. 2,124.3(d,J=3.4Hz),122.2,119.6,115.3(d,J=22.0Hz),89.2,78.5,77.3,77.0,76.7,36.0,31.3(d,J=3.4Hz),26.4,25.0,17.1. 19 F NMR(376MHz,CDCl3)δ(ppm)-119.6.HRMS(ESI):m / z[M+Na] + calcd for C 18 H 16 FNNaS:320.0880,found:320.0873.

[0224] Examples 39-58 provide a method for synthesizing chiral allene compounds.

[0225] Chiral allenes have the structural formula shown in general formula III:

[0226]

[0227] In the formula, R 2 Selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; R 4 Selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, 3-thiophene; R 5 It is selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl.

[0228] Chiral allenes having the above general formula III can have any of the following structures:

[0229]

[0230] The general formula for the synthesis of chiral allenes having the above-mentioned general structural formula III is as follows:

[0231]

[0232] In the general formula for synthesis, R 2 R 4 R 5 The definition and the general structural formula of chiral allene compounds R 2 R4 R 5 The definitions are the same; where Cu(CH3CN)4PF6 is cuprous tetraacetonitrile hexafluorophosphate, toluene is toluene, CH3CN is acetonitrile, CPME is cyclopentyl methyl ether, ee: enantiomeric excess, yield: yield.

[0233] In the general formula, the structure of arylboronic acid compound VI is the same as that in Examples 1-19, and the structure of 4-alkyl-1,3-enyne compound X can be any of the following structures:

[0234]

[0235] The specific synthetic steps for chiral allene compounds are as follows:

[0236] In a glove box, cuprous hexafluorophosphate tetraacetonitrile and ligand XI were dissolved in a mixed solvent of toluene, acetonitrile, and cyclopentyl methyl ether and stirred for 30 minutes. Then, 4-alkyl-1,3-enyne compound X, oxime ester substrate V, and arylboronic acid compound VI were added. After reacting under blue light at 0°C for 32 h, the target product with general formula III was directly obtained by column chromatography with petroleum ether / ethyl acetate (v:v) = 50:1–20:1.

[0237] Example 39

[0238] Preparation of compound III-1

[0239] Inside a glove box, copper salt Cu(CH3CN)4PF6 (1.86 mg, 0.0050 mmol, 5.0 mol%) and chiral ligand XI (4.70 mg, 0.0060 mmol, 6.0 mol%) were weighed and added to a glass vial. Then, 1.9 mL of toluene, 50 μL of acetonitrile, and 50 μL of cyclopentyl methyl ether solvent were added. The vial was tightly capped and stirred in the glove box for half an hour. Subsequently, arylboronic acid compound VI (0.1 mmol, 1.0 eq.), 4-alkyl-1,3-enyne compound X-1 (0.3 mmol, 3.0 eq.), and oxime ester V (0.2 mmol, 2.0 eq.) were added to the reaction flask, sealed, and removed from the glove box. The reaction flask was then transferred to an incubator (0 °C) and stirred under 20 W 456 nm Kessil LEDs illumination for 32 h. The reaction was then removed and monitored. After filtration through a filter head, the reaction system was washed with dichloromethane, concentrated, and an appropriate amount of silica gel powder was added. The target product III-1 was then separated by dry column chromatography (eluent: petroleum ether / ethyl acetate = 50:1 to 20:1).

[0240] Compound III-1 It was prepared using enyne X-1 and arylboronic acid VI-1 as substrates.

[0241] Yield 71%, enantiomeric excess 93% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 11.71 min, t R (minor) = 15.24 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.42-7.36 (m, 4H), 7.34-7.30 (m, 2H), 7.24-7.20 (m, 1H), 7.04-6.98 (m, 2H), 2.58-2. 53(m,4H),2.31(t,J=6.7Hz,2H),1.78-1.68(m,4H),1.57-1.52(m,2H),1.40-1.29(m,4H),0.85(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.6 (d, J = 1.9Hz), 161.9 (d, J = 246.5Hz), 135.0, 132.6, 132.1 (d, J = 3.4Hz), 128.6, 127.3 (d, J = 7. 9Hz), 127.1, 119.5, 115.5 (d, J = 21.5Hz), 109.3, 107.7, 77.3, 77.0, 76.7, 31.8, 30.3, 29.6, 27.7, 26.9, 25.2, 22.5, 17.0, 14.0. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.8.HRMS(ESI):m / z[M+Na] + calcd for C 25 H 28 FNNa:384.2098,found:384.2098.

[0242] Example 40

[0243] Preparation of compound III-2

[0244] The preparation steps are the same as in Example 39, except that compound III-2 It was prepared using enyne X-1 and arylboronic acid VI-2 as substrates.

[0245] Yield 60%, enantiomeric excess 96% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R(major) = 10.61 min, t R (minor) = 11.77 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.39-7.33 (m, 4H), 7.04-6.98 (m, 4H), 2.58-2.50 (m, 4H), 2.32 (t, J=6.8Hz,2H),1.79-1.61(m,4H),1.59-1.50(m,2H),1.40-1.26(m,4H),0.86(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.4 (t, J = 2.0Hz), 162.0 (d, J = 246.5Hz), 132.4 (d, J = 3.3Hz), 132.3 (d, J = 3.4Hz), 127.4 (d, J = 7.9Hz), 127.3 (d, J = 7.9Hz),119.5,115.5(d,J=21.3Hz),115.3(d,J=21.3Hz),109.3,107.4 ,77.3,77.0,76.7,31.8,30.5,29.6,27.7,26.9,25.2,22.5,17.0,14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.6.HRMS(ESI):m / z[M+Na] + calcd for C 25 H 27 F2NNa:402.2004,found:402.2005.

[0246] Example 41

[0247] Preparation of compound III-3

[0248] The preparation steps are the same as in Example 39, except that compound III-3 It was prepared using enyne X-1 and arylboronic acid VI-3 as substrates.

[0249] Yield 71%, enantiomeric excess 96% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 9.61 min, t R (minor) = 11.47 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.38-7.26 (m, 6H), 7.04-6.99 (m, 2H), 2.58-2.50 (m, 4H), 2.32 (t, J=6.7Hz,2H),1.79-1.65(m,4H),1.60-1.50(m,2H),1.40-1.28(m,4H),0.85(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.6 (d, J = 1.9Hz), 161.9 (d, J = 246.5Hz), 135.0, 132.6, 132.1 (d, J = 3.4Hz), 128.6, 127.3 (d, J = 7. 9Hz), 127.1, 119.5, 115.5 (d, J = 21.5Hz), 109.3, 107.7, 77.3, 77.0, 76.7, 31.8, 30.3, 29.6, 27.7, 26.9, 25.2, 22.5, 17.0, 14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.4.HRMS(ESI):m / z[M+Na] + calcd forC 25 H 27 ClFNNa:418.1708,found:418.1714.

[0250] Example 42

[0251] Preparation of compound III-4

[0252] The preparation steps are the same as in Example 39, except that compound III-4 It was prepared using enyne X-1 and arylboronic acid VI-4 as substrates.

[0253] Yield 69%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 10.27 min, t R (minor) = 11.22 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.45-7.41 (m, 2H), 7.38-7.33 (m, 2H), 7.27-7.24 (m, 2H), 7.04-6.98 (m, 2H), 2.59-2. 51(m,4H),2.32(t,J=6.7Hz,2H),1.78-1.65(m,4H),1.57-1.49(m,2H),1.40-1.26(m,4H),0.85(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.6 (d, J = 2.1Hz), 161.9 (d, J = 246.6Hz), 135.5, 132.0 (d, J = 3.3Hz), 131.6, 127.3 (d, J = 8.0Hz), 1 27.2,120.8,119.4,115.5(d,J=21.4Hz),109.4,107.7,77.3,77.0,76.7,31.8,30.2,29.6,27.7,26.9,25.2,22.5,17.0,14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.3.HRMS(ESI):m / z[M+Na] + calcd for C 25 H 27 BrFNNa:462.1203,found:462.1206.

[0254] Example 43

[0255] Preparation of compound III-5

[0256] The preparation steps are the same as in Example 39, except that compound III-5 It was prepared using enyne X-1 and arylboronic acid VI-5 as substrates.

[0257] Yield 44%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 15.05 min, t R (minor) = 16.84 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.59-7.55 (m, 4H), 7.49-7.31 (m, 7H), 7.05-6.99 (m, 2H), 2.60-2.57 (m, 4H ),2.34-2.31(m,2H),1.81-1.70(m,4H),1.65-1.57(m,2H),1.43-1.30(m,4H),0.87(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.9 (d, J = 2.1Hz), 161.9 (d, J = 246.3Hz), 140.6, 139.8, 135.4, 132.4 (d, J = 3.2Hz), 128.8, 127.3 (d, J = 7. 7Hz), 126.9, 126.2, 119.5, 115.4 (d, J = 21.4Hz), 109.8, 107.4, 77.3, 77.0, 76.7, 31.8, 30.3, 29.6, 27.8, 26.9, 25.2, 22.5, 17.0, 14.1. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.6.HRMS(ESI):m / z[M+H] + calcd for C 31 H 33 FN:438.2592, found:438.2592.

[0258] Example 44

[0259] Preparation of compound III-6

[0260] The preparation steps are the same as in Example 39, except that compound III-6 It was prepared using enyne X-1 and arylboronic acid VI-6 as substrates.

[0261] Yield 49%, enantiomeric excess 85% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.57 min, t R (minor) = 13.78 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.38-7.31 (m, 4H), 7.03-6.98 (m, 2H), 6.88-6.85 (m, 2H), 3.80 (s, 3H), 2.57-2.5 0(m,4H),2.32-2.29(m,2H),1.78-1.67(m,4H),1.58-1.49(m,2H),1.40-1.26(m,4H),0.85(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.1 (d, J = 2.0Hz), 161.8 (d, J = 246.1Hz), 158.7, 132.7 (d, J = 3.2Hz), 128.6, 127.2 (d, J = 7.9Hz), 126.9, 1 19.5,115.3(d,J=21.4Hz),114.0,113.9,109.6,107.0,77.3,77.0,76.7,55.3,31.8,30.5,29.6,27.8,26.9,25.2,22.5,17.0,14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.9.HRMS(ESI):m / z[M+Na] + calcd for C 26 H 30 FNNaO:414.2204,found:414.2204.

[0262] Example 45

[0263] Preparation of compound III-7

[0264] The preparation steps are the same as in Example 39, except that compound III-7 It was prepared using enyne X-1 and arylboronic acid VI-7 as substrates.

[0265] Yield 70%, enantiomeric excess 91% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.03 min, t R (minor) = 15.02 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.38-7.33 (m, 2H), 7.30-7.25 (m, 1H), 7.18 (d, J = 10.5Hz, 1H), 7.08 (dt, J = 10.6, 2.2Hz, 1H), 7.05-6.99 (m, 2H), 6 .94-6.89(m,1H),2.59-2.50(m,4H),2.33(t,J=6.7Hz,2H),1.80-1.65(m,4H),1.60-1.50(m,2H),1.41-1.25(m,4H),0.86(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.8 (d, J = 1.7Hz), 163.1 (d, J = 243.7Hz), 162.0 (d, J = 245.0Hz ),139.1(d,J=7.2Hz),132.0(d,J=3.4Hz),129.9(d,J=8.4Hz),127.3(d,J=7.9Hz),121.4(d ,J=2.7Hz),119.5,115.5(d,J=21.5Hz),113.7(d,J=21.3Hz),112.7(d,J=22.3Hz),109.4( d, J=2.6Hz),107.8,77.3,77.0,76.7,31.8,30.3,29.6,27.7,26.9,25.2,22.5,17.0,14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-113.1,-115.3.HRMS(ESI):m / z[M+Na] + calcd for C 25 H 27 F2NNa:402.2004,found:402.1992.

[0266] Example 46

[0267] Preparation of compound III-8

[0268] The preparation steps are the same as in Example 39, except that compound III-8 It was prepared using enyne X-1 and arylboronic acid VI-8 as substrates.

[0269] Yield 65%, enantiomeric excess 91% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R(major) = 13.69 min, t R (minor) = 17.49 min. 1 H NMR(400MHz, CDCl3)δ(ppm)7.51(t,J=1.8Hz,1H),7.38-7.31(m,4H),7.18(t,J=7.8Hz,1H),7.05-6.99(m,2H),2.59 -2.49(m,4H),2.33(t,J=6.1Hz,2H),1.81-1.65(m,4H),1.57-1.49(m,2H),1.41-1.25(m,4H),0.86(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.8 (d, J = 1.9Hz), 162.0 (d, J = 246.8Hz), 138.9, 132.0 (d, J = 3.3Hz), 130.0, 129.9, 128.7, 127.3 (d, J = 7. 9Hz), 124.5, 122.8, 119.4, 115.5 (d, J = 21.6Hz), 109.1, 107.9, 77.3, 77.0, 76.7, 31.7, 30.2, 29.6, 27.7, 26.9, 25.2, 22.5, 17.0, 14.0. 19 FNMR(376MHz,CDCl3)δ(ppm)-115.2.HRMS(ESI):m / z[M+Na] + calcd forC 25 H 27 BrFNNa:462.1203,found:462.1191.

[0270] Example 47

[0271] Preparation of compound III-9

[0272] The preparation steps are the same as in Example 39, except that compound III-9 It was prepared using enyne X-1 and arylboronic acid VI-9 as substrates.

[0273] Yield 42%, enantiomeric excess 82% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.10 min, t R (minor) = 23.89 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.66 (s, 1H), 7.60 (d, J = 7.9Hz, 1H), 7.49-7.43 (m, 3H), 7.29 (d, J = 7.3Hz, 1H), 7.13 (t, J = 7.5Hz, 1H), 7.03 (t, J = 8.7Hz, 2H),2.66-2.56(m,2H),2.52(t,J=7.7Hz,2H),2.32-2.28(m,2H),1.79-1 ,72(m,4H),1.66-1.58(m,2H),1.41-1.25(m,4H),0.86(t,J=6.9Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 203.9 (d, J = 2.0Hz), 161.9 (d, J = 246.6Hz), 155.6, 141.2, 132.7 (d, J = 3.3Hz), 127.6 (d, J = 7.9Hz), 126.0, 124.5, 1 23.0,120.7,119.5,117.4,115.5(d,J=21.5Hz),111.5,107.1,102.5, 77.3,77.0,76.7,31.8,31.6,29.9,27.6,26.9,25.2,22.5,17.0,14.0. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.5.HRMS(ESI):m / z[M+Na] + calcd for C 27 H 28 FNNaO:424.2047,found:424.2043.

[0274] Example 48

[0275] Preparation of compound III-10

[0276] The preparation steps are the same as in Example 39, except that compound III-10 It was prepared using enyne X-2 and arylboronic acid VI-1 as substrates.

[0277] Yield 73%, enantiomeric excess 88% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.42 min, t R (minor) = 17.98 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.44-7.41 (m, 4H), 7.34-7.30 (m, 4H), 7.24-7.19 (m, 2H), 2.61-2.54 (m, 4H) ,2.29(t,J=6.9Hz,2H),1.78-1.68(m,4H),1.61-1.52(m,2H),1.41-1.26(m,4H),0.86(t,J=7.0Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 205.0,136.6,136.5,128.5,128.5,126.9,125.9,125.8,119.6,109.8, 108.0,77.3,77.0,76.7,31.8,30.3,29.4,27.8,26.9,25.2,22.5,17.0,14.1.HRMS(ESI):m / z[M+H] + calcd forC 25 H 30 N:344.2374, found:344.2372.

[0278] Example 49

[0279] Preparation of compound III-11

[0280] The preparation steps are the same as in Example 39, except that compound III-11 It was prepared using enyne X-3 and arylboronic acid VI-1 as substrates.

[0281] Yield 60%, enantiomeric excess 93% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 12.37 min, t R (minor) = 16.01 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.45-7.37 (m, 4H), 7.34-7.27 (m, 4H), 7.25-7.21 (m, 1H), 2.57-2.53 (m, 4H) ,2.31(t,J=6.7Hz,2H),1.78-1.69(m,4H),1.58-1.50(m,2H),1.40-1.30(m,4H),0.86(t,J=7.1Hz,3H). 13C NMR (100MHz, CDCl3) δ (ppm) 205.0,136.2,135.5,131.6,128.6,127.3,127.1,125.9,120.7,119.5,110. 4,107.3,77.3,77.0,76.7,31.8,30.3,29.3,27.8,26.9,25.2,22.5,17.0,14.1.HRMS(ESI):m / z[M+Na] + calcdfor C 25 H 28 BrNNa:444.1297,found:444.1293.

[0282] Example 50

[0283] Preparation of compound III-12

[0284] The preparation steps are the same as in Example 39, except that compound III-12 It was prepared using enyne X-4 and arylboronic acid VI-1 as substrates.

[0285] Yield 79%, enantiomeric excess 86% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 10.95 min, t R (minor) = 13.77 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.41 (d, J = 8.9Hz, 2H), 7.33-7.29 (m, 4H), 7.24-7.19 (m, 1H), 7.13 (d, J = 8.0Hz, 2H), 2.58-2.5 2(m,4H),2.33(s,3H),2.30-2.27(m,2H),1.77-1.53(m,4H),1.61-1.53(m,2H),1.41-1.25(m,4H),0.86(t,J=7.0Hz,3H). 13 CNMR (100MHz, CDCl3) δ (ppm) 204.7,136.8,136.6,133.4,129.2,128.4,126.8,125.8,125.7,119.6,109.6, 107.8,77.3,77.0,76.7,31.9,30.3,29.4,27.8,26.9,25.2,22.5,21.0,17.0,14.1.HRMS(ESI):m / z[M+Na]+ calcd for C 26 H 31 NNa: 380.2349, found: 380.2349.

[0286] Example 51

[0287] Preparation of compound III-13

[0288] The preparation steps are the same as in Example 39, except that compound III-13 It was prepared using enyne X-5 and arylboronic acid VI-1 as substrates.

[0289] Yield 42%, enantiomeric excess 95% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 220 nm, 25 °C, retention time t R (major) = 17.58 min, t R (minor) = 18.55 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.58-7.56 (m, 1H), 7.49-7.46 (m, 2H), 7.35-7.25 (m, 4H), 7.23-7.19 (m, 1H), 7.14-7 .10(m,1H),2.53-2.47(m,4H),2.31(t,J=7.0Hz,2H),1.79-1.57(m,6H),1.39-1.32(m,4H),0.90-0.87(m,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 202.6, 139.4, 136.7, 133.1, 130.5, 128.6, 128.3, 127.4, 126.8, 126.2, 122.8, 119. 6,108.3,107.9,77.3,77.0,76.1,32.9,31.8,30.2,28.0,26.9,25.1,22.6,17.0,14.1.HRMS(ESI):m / z[M+Na] + calcd for C 25 H 28 BrNNa:444.1297,found:444.1292.

[0290] Example 52

[0291] Preparation of compound III-14

[0292] The preparation steps are the same as in Example 39, except that compound III-14 It was prepared using enyne X-6 and arylboronic acid VI-1 as substrates.

[0293] Yield 67%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 13.90 min, t R (minor) = 18.12 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.83-7.79 (m, 3H), 7.74 (d, J = 8.6Hz, 1H), 7.59 ( dd,J=8.6,1.8Hz,1H),7.49-7.42(m,4H),7.35-7.31(m,2H),7.25-7.21(m,1 H),2.73(t,J=6.9Hz,2H),2.60(t,J=7.6Hz,2H),2.33(t,J=6.8Hz,2H),1.8 5-1.75(m,4H),1.64-1.57(m,2H),1.44-1.26(m,4H),0.85(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 205.7,136.6,133.9,133.6,132.5,128.5,128.0,127.5,127.0,126.2,125.9,125.7,125.1,1 23.3,119.6,110.2,108.3,77.3,77.0,76.7,31.9,30.4,29.3,27.8,27.0,25.3,22.5,17.0,14.1.HRMS(ESI):m / z[M+Na] + calcd for C 29 H 31 NNa:416.2349, found:416.2344.

[0294] Example 53

[0295] Preparation of compound III-15

[0296] The preparation steps are the same as in Example 39, except that compound III-15 It was prepared using enyne X-7 and arylboronic acid VI-1 as substrates.

[0297] Yield 58%, enantiomeric excess 96% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 14.98 min, t R (minor) = 19.32 min. 1 H NMR (400MHz, CDCl3) δ (ppm) 7.41-7.39 (m, 2H), 7.33-7.29 (m, 2H), 7.25-7.19 (m, 2H), 7.12-7.10 (m, 2H), 2.57-2 .52(m,4H),2.31-2.27(m,2H),1.77-1.71(m,4H),1.61-1.53(m,2H),1.41-1.29(m,4H),0.86(t,J=7.1Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.7, 138.5, 136.7, 128.5, 126.9, 126.7, 126.0, 125.5, 119.5, 118.8, 109. 5,104.3,77.3,77.0,76.7,31.8,30.5,30.1,27.9,26.8,25.2,22.5,17.0,14.1.HRMS(ESI):m / z[M+Na] + calcd for C 23 H 27 NNaS: 372.1756, found: 372.1756.

[0298] Example 54

[0299] Preparation of compound III-16

[0300] The preparation steps are the same as in Example 39, except that compound III-16 It was prepared using enyne X-8 and arylboronic acid VI-2 as substrates.

[0301] Yield 68%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 95:5, v:v), 0.5 mL / min, 220 nm, 25 °C, retention time t R (major) = 12.30 min, t R (minor) = 15.74 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.42-7.30 (m, 6H), 7.25-7.20 (m, 1H), 7.04-6.98 (m, 2H), 2.59-2.54 (m, 4H ),2.33-2.29(m,2H),1.79-1.67(m,4H),1.56-1.50(m,3H),1.46-1.37(m,2H),0.91(t,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.7 (d, J = 1.9Hz), 161.8 (d, J = 240.9Hz), 136.5, 132.4 (d, J = 3.7Hz), 128.5, 127.2 (d, J = 8.0Hz) ,127.0,125.8,119.5,115.4(d,J=21.5Hz),110.1,107.2,77.3,77.0,76.7,30.3,30.1,29.6,26.9,25.2,22.7,17.0,14.0. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.7.HRMS(ESI):m / z[M+Na] + calcd for C 24 H 26 FNNa:370.1941,found:370.1941.

[0302] Example 55

[0303] Preparation of compound III-17

[0304] The preparation steps are the same as in Example 39, except that compound III-17 It was prepared using enyne X-9 and arylboronic acid VI-2 as substrates.

[0305] Yield 70%, enantiomeric excess 90% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 220 nm, 25 °C, retention time t R (major) = 11.15 min, t R (minor) = 14.47 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.42-7.30 (m, 6H), 7.25-7.20 (m, 1H), 7.04-6.99 (m, 2H), 2.58-2.53 (m, 4H), 2.31 (t, J=6.6Hz,2H),1.76-1.67(m,4H),1.60-1.51(m,2H),1.43-1.35(m,2H),1.30-1.25(m,4H),0.85(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.7 (d, J = 1.8Hz), 161.9 (d, J = 244.8Hz), 136.5, 132.4 (d, J = 3.4Hz), 128.5, 127.2 (d, J = 7.9Hz), 127. 0,125.8,119.5,115.4(d,J=21.4Hz),110.1,107.2,77.3,77.0,76.3,31.7,30.4,29.6,29.4,28.1,26.9,25.2,22.7,17.0,14.0. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.7.HRMS(ESI):m / z[M+Na] + calcd for C 26 H 30 FNNa:398.2254,found:398.2254.

[0306] Example 56

[0307] Preparation of compound III-18

[0308] The preparation steps are the same as in Example 39, except that compound III-18 It was prepared using enyne X-10 and arylboronic acid VI-2 as substrates.

[0309] Yield 66%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis using a chiral AD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 11.96 min, t R (minor) = 13.42 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.43-7.40 (m, 2H), 7.39-7.32 (m, 4H), 7.27-7.22 (m, 1H), 7.05-6.99 (m, 2H), 3.61 (t ,J=6.4Hz,2H),2.76-2.72(m,2H),2.60-2.56(m,2H),2.34-2.30(m,2H),2.10-2.00(m,2H),1.78-1.70(m,4H). 13 C NMR (100MHz, CDCl3) δ (ppm) 204.4 (d, J = 2.1Hz), 161.9 (d, J = 245.3Hz), 135.9, 132.0 (d, J = 3.2Hz), 128.7, 127.3, 127.3 (d ,J=3.3Hz),125.8,119.5,115.5(d,J=21.4Hz),108.8,108.2,77.3,77.0,76.6,44.7,30.9,29.7,27.6,26.9,25.2,17.0. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.2.HRMS(ESI):m / z[M+Na] + calcd for C 23 H 23 ClFNNa:390.1395,found:390.1395.

[0310] Example 57

[0311] Preparation of compound III-19

[0312] The preparation steps are the same as in Example 39, except that compound III-19 It was prepared using enyne X-11 and arylboronic acid VI-2 as substrates.

[0313] Yield 75%, enantiomeric excess 92% (determined by chiral HPLC; HPLC analysis by chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 11.11 min, t R (minor) = 12.54 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.41-7.30 (m, 6H), 7.24-7.20 (m, 1H), 7.03-6.97 (m, 2H), 2.60-2.54 (m, 2H), 2.50 -2.39(m,2H),2.32-2.27(m,2H),1.82-1.58(m,9H),1.55-1.49(m,1H),1.26-1.08(m,3H),1.01-0.91(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 205.3 (d, J = 1.9Hz), 161.8 (d, J = 246.3Hz), 136.6, 132.5 (d, J = 3.3Hz), 128.5, 127.4 (d, J = 7.8Hz), 126.9, 126.1,119.5,115.4(d,J=21.4Hz),108.1,106.0,77.3,77.0,76.7,38.6,36.3,33.6,33.5,29.8,27.0,26.4,26.2,26.1,25.2,17.0. 19 F NMR(376MHz,CDCl3)δ(ppm)-115.7.HRMS(ESI):m / z[M+Na] + calcd for C 27 H 30 FNNa:410.2254,found:410.2250.

[0314] Example 58

[0315] Preparation of Compound III-20

[0316] The preparation steps are the same as in Example 39, except that compound III-20 It was prepared using enyne X-12 and arylboronic acid VI-2 as substrates.

[0317] Yield 62%, enantiomeric excess 86% (determined by chiral HPLC; HPLC analysis using a chiral OD-H column, isopropanol:n-hexane 90:10, v:v), 0.5 mL / min, 254 nm, 25 °C, retention time t R (major) = 17.43 min, t R (minor) = 24.02 min. 1H NMR (400MHz, CDCl3) δ (ppm) 7.58-7.55 (m, 2H), 7.36-7.30 (m, 4H), 7.27-7.22 (m, 1H), 7.02-6.96 (m, 2H) ,2.55(t,J=7.1Hz,2H),2.31(t,J=6.9Hz,2H),1.79-1.61(m,5H),0.95-0.87(m,2H),0.58-0.50(m,2H). 13 C NMR (100MHz, CDCl3) δ (ppm) 203.7 (d, J = 2.0Hz), 161.9 (d, J = 246.5Hz), 136.7, 132.1 (d, J = 3.3Hz), 128.5, 127.2, 127.1 ( d,J=7.9Hz),126.1,119.5,115.4(d,J=21.4Hz),113.2,108.5,77.3,77.0,76.7,29.5,26.8,25.1,17.0,11.3,7.0,6.8. 19 F NMR(376MHz, CDCl3)δ(ppm)-115.4.HRMS(ESI):m / z[M+Na] + calcd for C 23 H 22 FNNa:354.1628,found:354.1621.

[0318] Comparative Example 1

[0319] The preparation steps were the same as in Example 20, except that the reaction was not carried out under 20W 390nm Kessil LEDs illumination, and the yield was 10%, with an enantiomeric excess of 89%.

[0320] Comparative Example 2

[0321] The preparation steps were the same as in Example 39, except that the reaction was not carried out under 20W 456nm Kessil LEDs illumination, and the yield was 55%, with an enantiomeric excess of 93%.

[0322] Comparative Example 3

[0323] The preparation steps were the same as in Example 20, except that the reaction was carried out under 20W 456nm Kessil LEDs illumination, with a yield of 50% and an enantiomeric excess of 85%.

[0324] Comparative Example 4

[0325] The preparation steps were the same as in Example 39, except that the reaction was carried out under 20W 390nm Kessil LEDs illumination, with a yield of 54% and an enantiomeric excess of 85%.

[0326] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids, characterized in that, Includes the following steps: The copper catalyst and the bisoxazoline ligand were dissolved in a mixed solvent and stirred until homogeneous. Unsaturated hydrocarbon substrates, oxime ester substrates and arylboronic acid compounds were added, and the reaction was carried out at 0°C for 12-32 h. The unsaturated hydrocarbon substrates include one of the following: olefins, 4-aryl-1,3-enyne compounds, or 4-alkyl-1,3-enyne compounds; The general structural formula of the olefin compounds is: ； R 1 Selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene; The general structural formula of the 4-aryl-1,3-enyne compounds is: ； R 3 It is selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, and 3-thiopheneyl; The general structural formula of the 4-alkyl-1,3-enyne compounds is: ； R 4 It is selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, and 3-thiophene; R 5 Selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl; The structure of the oxime ester substrate is as follows: ； The general structural formula of the arylboronic acid compounds is: ； R 2 It is selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; The general structural formula of the chiral aryl compound is selected from one of the following: 、 、 ； The synthesis reaction of the chiral aryl compound is shown in the following reaction: ； ； ； In the formula, R 1 Selected from one of 2-naphthyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-cyanophenyl, 4-biphenyl, 3-methoxyphenyl, 3-chlorophenyl, 3-thienyl, benzothiophene, benzofuran, and phenanthrene; R 2 Selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-biphenyl, 4-methoxyphenyl, 3-fluorophenyl, 3-bromophenyl, and benzofuran; R 3 Selected from one of phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl ester phenyl, 4-biphenyl, 4-tert-butylphenyl, 2-bromophenyl, 3-chlorophenyl, 3-methylphenyl, 3-thiopheneyl; R 4 Selected from one of phenyl, 4-bromophenyl, 4-methylphenyl, 2-bromophenyl, 2-naphthyl, 3-thiophene; R 5 Selected from one of butyl, n-heptyl, chloropropane, methylenecyclohexyl, and cyclopropyl; The structural formula of the bisoxazoline ligand is one of the following: 、 、 ； The copper catalyst is cuprous tetraacetonitrile hexafluorophosphate or cuprous tetraacetonitrile trifluoromethanesulfonate.

2. The method for synthesizing chiral aryl compounds based on unsaturated hydrocarbons, oxime esters, and arylboronic acids according to claim 1, characterized in that, The mixed solvent includes at least one of toluene, acetonitrile, tetrahydrofuran, and cyclopentyl methyl ether.

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