Chiral allyl azide compound and method for preparing the same

Abstract

This invention discloses an alkyl azido chiral allyl ester compound and its preparation method, belonging to the field of organic synthesis technology. This invention employs UV-Vis light-induced copper tetraacetonitrile hexafluorophosphate-catalyzed reaction of a diene, a high-valent iodine azide reagent, and a carboxylic acid to obtain an alkyl azido chiral allyl ester compound having the following general structural formula: R 1 Selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl, or thiazolyl; R 2 The compounds are selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperonyl, furanyl, 2-(5-methyl)thiophene, phenylethynyl, propanesulfonyl, atalulenyl, adapaleneyl, bicyclo[1.1.1]pentane (BCP)carboxylate methyl ester and bicyclo[2.2.2]octanecarboxylate methyl ester or benzyl ester. The alkyl azido chiral allyl ester compounds of the present invention exhibit high enantioselectivity and broad applications.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to an alkyl azido chiral allyl ester compound and its preparation method. Background Technology

[0002] Azides are an important class of organic nitrogen-containing compounds, serving as precursors to various nitrogen-containing derivatives and finding wide application in the pharmaceutical field. Different nitrogen-containing compounds exhibit significantly different pharmacological activities. Alkyl azidoides are a special class of functional motifs, not only ubiquitous in many bioactive compounds and drugs but also serving as general intermediates and building blocks for synthesizing various therapeutically significant nitrogen-containing scaffolds and bioactive molecules. Alkyl azidochiral allyl esters are a class of chiral heterocyclic compounds containing two different types of heteroatoms (nitrogen and oxygen). Traditional methods for their synthesis primarily rely on nucleophilic substitution / addition of inorganic azides to electrophilic substrates, and the diazo transfer reaction of trifluoromethanesulfonyl azides (TfN3) to primary amines. However, these methods often yield mixed products, exhibiting low enantioselectivity and limiting their applications. Therefore, inventing a synthetic method for alkyl azidochiral allyl esters with high enantioselectivity is of great significance. Summary of the Invention

[0003] To address the shortcomings of existing technologies, this invention provides an alkyl azido chiral allyl ester compound and its preparation method. The alkyl azido chiral allyl ester compound prepared by the method of this invention exhibits high enantioselectivity and wide applicability. Specifically, it is achieved through the following techniques.

[0004] An alkyl azide chiral allyl ester compound has the following general structural formula:

[0005]

[0006] R 1 Selected from phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazole or any one thereof;

[0007] R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, propanesulfonyl, atalulenyl, adapaleneyl, bicyclo[1.1.1]pentane(BCP)carboxylic acid methyl ester and bicyclo[2.2.2]octanecarboxylic acid methyl ester or benzoyl ester.

[0008] Preferably, the alkyl-substituted phenyl group is selected from any one of 4-methylphenyl, 4-tert-butylphenyl, 3-methylphenyl or 2-methylphenyl.

[0009] Preferably, the aryl-substituted phenyl group is 4-phenylphenyl.

[0010] Preferably, the halophenyl group is selected from any one of 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 4-chlorophenyl, or 4-bromophenyl.

[0011] The preparation method of the above-mentioned alkyl azide chiral allyl ester compound includes the following steps:

[0012] The catalyst and benzofuran oxazoline ligand were dissolved in an organic solvent and stirred under inert gas protection to obtain mixture I;

[0013] Diene, high-valent iodine azide reagent and carboxylic acid are added to the mixture I and degassed to obtain mixture II;

[0014] Mixture II was placed under ultraviolet light for further reaction, and the alkyl azide chiral allyl ester compound was isolated.

[0015] Preferably, the diene has the following general structural formula: R 1 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazolyl.

[0016] More preferably, the diene is selected from any one of phenyl-substituted 1,3-diene, 4-methylphenyl-substituted 1,3-diene, 4-tert-butylphenyl-substituted 1,3-diene, 4-phenylphenyl-substituted 1,3-diene, 4-chlorophenyl-substituted 1,3-diene, 4-bromophenyl-substituted 1,3-diene, 3-methylphenyl-substituted 1,3-diene, 3-methoxyphenyl-substituted 1,3-diene, 3-chlorophenyl-substituted 1,3-diene, 3-bromophenyl-substituted 1,3-diene, 2-methylphenyl-substituted 1,3-diene, 2-methoxyphenyl-substituted 1,3-diene, 2-fluorophenyl-substituted 1,3-diene, 2-naphthyl-substituted 1,3-diene, and 3-thiophene-substituted 1,3-diene.

[0017] Preferably, the general structural formula of the carboxylic acid is R. 2 -CO2H, R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, propanesulfonyl, atalulenyl, adapaleneyl, bicyclo[1.1.1]pentane(BCP)carboxylic acid methyl ester and bicyclo[2.2.2]octanecarboxylic acid methyl ester or benzoyl ester.

[0018] More preferably, the carboxylic acid is selected from monomethyl terephthalate, benzoic acid, 4-methylbenzoic acid, 4-tert-butylbenzoic acid, 4-phenylbenzoic acid, 4-chlorobenzoic acid, 4-bromobenzoic acid, 3-methoxybenzoic acid, 3-fluorobenzoic acid, 2-methylbenzoic acid, 2-chlorobenzoic acid, piperic acid, 2-chloro-4-fluorobenzoic acid, 2-furanic acid, 5-methylthiophenic acid, phenylpropynic acid, probenecid, atalulin, adapalene, bicyclo[1.1.1]pentane (BCP) dicarboxylic acid monomethyl ester, and bicyclo[2.2.2]octane dicarboxylic acid monomethyl ester.

[0019] Preferably, the high-valent iodine azide reagent is azide benzyldiazolone reagent, with the following structural formula: In NTs, N represents nitrogen and Ts represents p-toluenesulfonyl group.

[0020] Preferably, the catalyst is copper tetraacetonitrile hexafluorophosphate.

[0021] Preferably, the benzofuran oxazoline ligand is a 3,5-di-tert-butyl-modified aryl-substituted benzofuran oxazoline ligand with the following structural formula:

[0022]

[0023] The reaction formula for synthesizing the alkyl azide chiral allyl ester compound in the above preparation method is as follows:

[0024]

[0025] R 1 Selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazolyl;

[0026] R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, propanesulfonyl, atalulenyl, adapaleneyl, bicyclo[1.1.1]pentane(BCP)carboxylic acid methyl ester and bicyclo[2.2.2]octanecarboxylic acid methyl ester or benzoyl ester.

[0027] Compared with the prior art, the advantages of the present invention are:

[0028] This invention employs UV-Vis light-induced copper catalyst to catalyze the reaction of carboxylic acids, dienes, and azide reagents, in conjunction with chiral NNO ligands. During the reaction, the carboxylic acid forms ester bonds. The structural changes of the chiral NNO ligands can modulate the azide radical generation rate and stereoinduction in CO cross-coupling, thereby improving the enantioselectivity of the product. The preparation method of this invention features mild reaction conditions, simple operation, and high enantioselectivity for the target product, an alkyl azide chiral allyl ester compound, making it widely applicable. Detailed Implementation

[0029] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention. To further illustrate this invention, the technical solutions provided by this invention are described in detail below with reference to embodiments, but these should not be construed as limiting the scope of protection of this invention.

[0030] The method for preparing the alkyl azide chiral allyl ester compound provided in the following examples includes the following steps:

[0031] At room temperature, the catalyst copper hexafluorophosphate tetraacetonitrile and ligand L were dissolved in 2 ml of dichloromethane and stirred for 30 minutes under argon protection. Then, 1,3-diene II, azidobenzyldiazolone reagent III, and carboxylic acid IV were added, followed by degassing three times under liquid nitrogen conditions. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC analysis showed complete reaction. The resulting products were separated by silica gel column chromatography. In the eluent, V... 石油醚 / V 乙酸乙酯 The ratios were adjusted sequentially in the order of 100:1, 50:1, 30:1, and 10:1 to finally obtain the target product of this invention.

[0032] The reaction formulas involved are shown below:

[0033]

[0034] In the above reaction formula, R 1 Selected from phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazole or any one thereof;

[0035] R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, propanesulfonyl, atalulenyl, adapaleneyl, bicyclo[1.1.1]pentane(BCP)carboxylic acid methyl ester and bicyclo[2.2.2]octanecarboxylic acid methyl ester or benzoyl ester.

[0036] Among them, Cu(CH3CN)PF6 is copper tetraacetonitrile hexafluorophosphate; DCM is dichloromethane; and ligand is a 3,5-di-tert-butyl-modified aryl-substituted benzofuranoxazolin ligand.

[0037] The technical solution of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0038] Example 1

[0039] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0040] At room temperature, copper tetraacetonitrile hexafluorophosphate catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-1 with a yield of 80% and an enantioselectivity (ee) of 96%.

[0041]

[0042] 1 HNMR (400MHz, CDCl3) δ (ppm) 8.18-8.10 (m, 4H), 7.41 (d, J = 9.7Hz, 2H), 7.36-7.27 (m, 3H), 6.82 ( d,J=16.0Hz,1H),6.27(dd,J=16.0,7.3Hz,1H),5.85(m,1H),3.95(s,3H),3.64(d,J=5.3Hz,2H).

[0043] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.7, 135.5, 135.2, 134.2, 133.5, 129.7, 129.6, 128.6, 128.5, 126.8, 123.1, 74.5, 54.1, 52.5.

[0044] High resolution: Calculated value: [M+Na] + 374.1111, Measured value: 374.1115.

[0045] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 14.17 min, t R (minor) = 23.55 min.

[0046] Example 2

[0047] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0048] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, 4-methylphenyl-substituted 1,3-diene II-2 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and terephthalic acid were added. Monomethyl ester IV-1 (0.1 mmol, 1.0 equiv.) was degassed three times under liquid nitrogen conditions; then, it was reacted under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1 to finally obtain the target product of formula I-2 with a yield of 75% and an enantioselectivity (ee) of 93%.

[0049]

[0050] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.20-8.09 (m, 4H), 7.33-7.27 (m, 2H), 7.13 (d, J = 7.9Hz, 2H), 6.78 (d, J = 15.9H z,1H),6.21(dd,J=15.9,7.4Hz,1H),5.90-5.77(m,1H),3.95(s,3H),3.63(d,J=5.3Hz,2H),2.33(s,3H).

[0051] 13C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.8, 138.5, 135.2, 134.2, 133.5, 132.7, 129.7, 129.6, 129.3, 126.7, 122.0, 74.7, 54.2, 52.5, 21.2.

[0052] High resolution: Calculated value: [M+Na] + 388.1268, measured value: 388.1271.

[0053] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 10.60 min, t R (minor) = 14.11 min.

[0054] Example 3

[0055] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0056] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 4-tert-butylphenyl-substituted 1,3-diene II-3 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-3 with a yield of 69% and an enantioselectivity (ee) of 93%.

[0057]

[0058] 1H NMR (400MHz, CDCl3) δ (ppm) 8.17-8.11 (m, 4H), 7.35 (s, 4H), 6.80 (d, J = 15.9Hz, 1H), 6.23 (dd ,J=15.9,7.4Hz,1H),5.84(q,J=5.9Hz,1H),3.95(s,3H),3.63(d,J=5.3Hz,2H),1.31(s,9H).

[0059] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.7, 151.8, 135.1, 134.2, 133.6, 132.7, 129.7, 129.6, 126.5, 125.6122.3, 74.7, 54.2, 52.5, 34.6, 31.2.

[0060] High resolution: Calculated value: [M+Na] + :430.1737, measured value: 430.1738.

[0061] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 10.79 min, t R (minor) = 15.00 min.

[0062] Example 4

[0063] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0064] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 4-phenylphenyl-substituted 1,3-diene II-4 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-4 with a yield of 71% and an enantioselectivity (ee) of 85%.

[0065]

[0066] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.20-8.12 (m, 4H), 7.61-7.56 (m, 4H), 7.50-7.47 (m, 2H), 7.46-7.42 (m, 2H), 7.37-7.33 ( m,1H),6.86(d,J=15.9Hz,1H),6.32(dd,J=15.9,7.3Hz,1H),5.93-5.82(m,1H),3.96(s,3H),3.66(d,J=5.3Hz,2H).

[0067] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2,164.8,141.3,140.4,134.8,134.5,134.2,13 3.5,129.8,129.6,128.8,127.5,127.3,127.2,126.9,123.1,74.6,54.1,52.5.

[0068] High resolution: Calculated value: [M+Na] + :450.1424, measured value: 450.1432.

[0069] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R(major) = 31.53 min, t R (minor) = 37.97min.

[0070] Example 5

[0071] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0072] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 4-chlorophenyl-substituted 1,3-diene II-5 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-AB Z) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, to finally obtain the target product of formula I-5 with a yield of 58% and an enantioselectivity (ee) of 96%.

[0073]

[0074] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.13 (m, 4H), 7.33 (d, J = 8.7Hz, 2H), 7.29 (d, J = 8.4Hz, 2H), 6.76 (d, J = 16.0H z,1H),6.24(dd,J=15.9,7.3Hz,1H),5.83(dd,J=11.9,5.8Hz,1H),3.95(s,3H),3.64(d,J=6.4Hz,2H).

[0075] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.7, 134.3, 134.2, 134.0, 133.9, 133.4, 129.8, 129.7, 128.8, 128.0, 123.8, 74.4, 54.0, 52.5.

[0076] High resolution: Calculated value: [M+Na] + :408.0722, measured value: 408.0729.

[0077] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 12.22 min, t R (minor) = 15.52 min.

[0078] Example 6

[0079] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0080] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 4-bromophenyl-substituted 1,3-diene II-6 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-AB Z) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, finally yielding the target product of formula I-6 with a yield of 63% and an enantioselectivity (ee) of 96%.

[0081]

[0082] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.24-8.12 (m, 4H), 7.51-7.47 (m, 2H), 7.32-7.29 (m, 2H), 6.78 (d, J = 15. 9Hz,1H),6.30(dd,J=16.0,7.2Hz,1H),5.91-5.80(m,1H),3.99(s,3H),3.67(dd,J=5.2,2.0Hz,2H).

[0083] 13C NMR (100MHz, CDCl3) δ (ppm) 166.1, 164.7, 134.5, 134.7, 133.9, 133.3, 131.8, 129.8, 129.7, 128.3, 124.0, 122.4, 74.3, 54.0, 52.5.

[0084] High resolution: Calculated value: [M+Na] + :452.0216, Measured value: 452.0228.

[0085] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 13.24 min, t R (minor) = 16.59 min.

[0086] Example 7

[0087] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0088] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 3-methylphenyl-substituted 1,3-diene II-7 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-7 with a yield of 80% and an enantioselectivity (ee) of 96%.

[0089]

[0090] 1H NMR (400MHz, CDCl3) δ (ppm) 8.14 (m, 4H), 7.22 (d, J = 7.2Hz, 3H), 7.09 (d, J = 6.5Hz, 1H), 6.78 (d, J = 15.9Hz, 1H), 6.26 (dd, J=16.0, 7.3Hz, 1H), 5.84 (q, J=6.5Hz, 1H), 3.95 (s, 3H), 3.64 (d, J=3.9Hz, 2H), 2.34 (s, 3H).

[0091] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.8, 138.3, 135.5, 135.6, 134.2, 133. 6,129.8,129.7,129.4,128.6,127.5,124.0,122.9,74.7,54.2,52.5,21.4.

[0092] High resolution: Calculated value: [M+Na] + 388.1268, measured value: 388.1280.

[0093] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 10.58 min, t R (minor) = 16.20 min.

[0094] Example 8

[0095] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0096] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 3-methoxyphenyl-substituted 1,3-diene II-8 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-8 with a yield of 67% and an enantioselectivity (ee) of 95%.

[0097]

[0098] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.22-8.14 (m, 4H), 7.29 (d, J = 7.8Hz, 1H), 7.04 (d, J = 8.0Hz, 1H), 6.97 (t, J = 2.0Hz, 1H), 6. 89-6.79(m,2H),6.30(dd,J=15.9,7.3Hz,1H),5.88(q,J=5.7Hz,1H),3.99(s,3H),3.85(s,3H),3.68(d,J=5.3Hz,2H).

[0099] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.7, 159.8, 136.9, 135.1, 134.2, 133. 5,129.7,129.6,129.6,123.4,119.4,114.3,111.9,74.8,55.2,54.1,52.5.

[0100] High resolution: Calculated value: [M+Na] + :404.1217, measured value: 404.1230.

[0101] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R(major) = 28.74 min, t R (minor) = 52.23 min.

[0102] Example 9

[0103] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0104] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 3-chlorophenyl-substituted 1,3-diene II-9 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-AB Z) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-9 with a yield of 62% and an enantioselectivity (ee) of 96%.

[0105]

[0106] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.11-8.03 (m, 4H), 7.32 (d, J = 1.5 Hz, 1H), 7.18 (m, 3H), 6.69 (d, J = 1 .0Hz,1H),6.21(dd,J=16.0,7.1Hz,1H),5.76(m,1H),3.87(s,3H),3.56(dd,J=5.2,2.3Hz,2H).

[0107] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.1, 164.7, 137.4, 134.6, 134.3, 133.6, 133.3, 129.9, 129.7, 129.6, 128.4, 126.6, 125.0, 124.8, 74.2, 54.0, 52.5.

[0108] High resolution: Calculated value: [M+Na] + :408.0722, measured value: 408.0731.

[0109] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=220nm, 25℃), t R (major) = 13.39 min, t R (minor) = 15.09 min.

[0110] Example 10

[0111] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0112] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 3-bromophenyl-substituted 1,3-diene II-10 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-10 with a yield of 61% and an enantioselectivity (ee) of 90%.

[0113]

[0114] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.17-8.10 (m, 4H), 7.55 (t, J = 1.9Hz, 1H), 7.39 (m, 1H), 7.30 (m, 1H), 7.19 (t, J = 7.8Hz, 1H), 6. 73(d,J=15.9Hz,1H),6.27(dd,J=15.9,7.1Hz,1H),5.83(dd,J=7.1,1.1Hz,1H),3.95(s,3H),3.64(dd,J=5.3,2.5Hz,2H).

[0115] 13C NMR (100MHz, CDCl3) δ (ppm) 166.1, 164.7, 137.6, 134.3, 133.5, 133.3, 131.3, 130.1, 129.7, 129.6, 129.5, 125.5, 124.8, 122.8, 74.2, 54.0, 52.5.

[0116] High resolution: Calculated value: [M+Na] + :452.0216, Measured value: 452.0223.

[0117] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 15.77 min, t R (minor) = 26.36 min.

[0118] Example 11

[0119] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0120] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 2-methylphenyl-substituted 1,3-diene II-11 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-11 with a yield of 70% and an enantioselectivity (ee) of 80%.

[0121]

[0122] 1H NMR(400MHz, CDCl3)δ(ppm)8.17-8.11(m,4H),7.45(dd,J=7.1,2.0Hz,1H),7.21-7.13(m,3H),7.06(dd,J=15.8 ,1.0Hz,1H),6.15(dd,J=15.8,7.4Hz,1H),5.92-5.82(m,1H),3.95(s,3H),3.65(d,J=5.3Hz,2H),2.35(s,3H).

[0123] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.7, 135.9, 134.6, 134.2, 133.5, 133. 2,130.4,129.7,129.6,128.4,126.2,125.7,124.4,74.8,54.1,52.5,19.7.

[0124] High resolution: Calculated value: [M+Na] + 388.1268, Measured value: 388.1279

[0125] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 13.98 min, t R (minor) = 16.55 min.

[0126] Example 12

[0127] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0128] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 2-methoxyphenyl-substituted 1,3-diene II-12 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-12 with a yield of 65% and an enantioselectivity (ee) of 91%.

[0129]

[0130] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.15 (t, J = 9.7Hz, 4H), 7.46 (d, J = 6.9Hz, 1H), 7.29 (d, J = 7.6Hz, 1H), 7.15 (d, J = 16.0Hz, 1H), 6.95 (q, J = 8 .6Hz,1H),6.89(d,J=8.2Hz,1H),6.34(dd,J=15.4,6.7Hz,1H),5.92-5.83(m,1H),3.97(s,3H),3.87(s,3H),3.66(d,J=5.1Hz,2H).

[0131] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.2, 164.8, 157.1, 134.1, 133.7, 130.3, 129. 8,129.6,129.6,127.3,124.4,123.6,120.6,110.9,75.1,55.4,54.3,52.5.

[0132] High resolution: Calculated value: [M+Na] + 404.1217, measured value: 404.1220.

[0133] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), tR(major)=18.91min, tR(minor)=35.14min.

[0134] Example 13

[0135] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0136] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 2-fluorophenyl-substituted 1,3-diene II-13 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen conditions. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-13 with a yield of 60% and an enantioselectivity (ee) of 97%.

[0137]

[0138] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.13-8.03 (m, 4H), 7.38 (t, J = 8.5Hz, 1H), 7.20-7.15 (m, 1H), 7.03 (t, J = 7.8Hz, 1H), 7.00-6. 94(m,1H),6.87(d,J=15.9Hz,1H),6.31(dd,J=16.2,7.1Hz,1H),5.78(q,J=5.1Hz,1H),3.88(s,3H),3.63-3.53(m,2H).

[0139] 13C NMR (100MHz, CDCl3) δ (ppm) 165.5 (d, J = 147.2Hz), 160.49 (d, J = 250.7Hz), 134.3, 133.4, 129.9 (d, J = 12.3Hz), 129.7, 127. 9(d,J=3.5Hz),127.7(d,J=3.2Hz),126.0(d,J=5.8Hz),124.2(d,J=3.5Hz),123.5,123.3,116.0,115.8,74.6,54.1,52.5.

[0140] 19 F NMR(376MHz, CDCl3)δ(ppm)-116.95.

[0141] High resolution: Calculated value: [M+Na] + 392.1017, measured value: 392.1024.

[0142] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 10.37 min, t R (minor) = 15.95 min.

[0143] Example 14

[0144] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0145] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 2-naphthyl-substituted 1,3-diene II-14 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, finally yielding the target product of formula I-14 with a yield of 68% and an enantioselectivity (ee) of 93%.

[0146]

[0147] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.21-8.12 (m, 4H), 7.83-7.77 (m, 4H), 7.60 (dd, J = 8.6, 1.8Hz, 1H), 7.48-7.43 (m, 2H ),6.98(d,J=15.9Hz,1H),6.39(dd,J=15.9,7.3Hz,1H),5.95-5.86(m,1H),3.95(s,3H),3.68(d,J=5.2Hz,2H).

[0148] 13 C NMR (100MHz, CDCl3) δ (ppm) 66.2,164.8,135.3,134.2,133.5,133.4,133.4,133.0,12 9.8,129.7,128.4,128.1,127.7,127.4,126.5,126.4,123.4,123.3,74.6,54.2,52.5.

[0149] High resolution: Calculated value: [M+Na] + :424.1268, Measured value: 424.1265.

[0150] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=250nm, 25℃), t R (major) = 20.07 min, t R (minor) = 23.29 min.

[0151] Example 15

[0152] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0153] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, 3-thiophene-substituted 1,3-diene II-15 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and monomethyl terephthalate IV-1 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-15 with a yield of 60% and an enantioselectivity (ee) of 83%.

[0154]

[0155] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.16-8.11 (m, 4H), 7.28 (dd, J = 5.1, 3.0Hz, 1H), 7.25-7.21 (m, 2H), 6.82 (d ,J=15.8Hz,1H),6.11(dd,J=15.9,7.4Hz,1H),5.86-5.75(m,1H),3.95(s,3H),3.62(d,J=5.3Hz,2H).

[0156] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.1, 164.7, 138.2, 134.2, 133.5, 129.7, 129.6, 129.3, 126.4, 124.8, 124.0, 122.8, 74.6, 54.1, 52.5.

[0157] High resolution: Calculated value: [M+Na] + 380.0675, measured value: 380.0677.

[0158] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major)=16.58min, tR(minor)=24.71min.

[0159] Example 16

[0160] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0161] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and benzoic acid IV-2 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-16 in 80% yield with an enantioselectivity (ee) of 95%.

[0162]

[0163] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.11 (dd, J = 8.3, 1.4Hz, 2H), 7.59 (t, J = 7.4Hz, 1H), 7.47 (t, J = 7.7Hz, 2H), 7.42-7.39 (m, 2H), 7.35- 7.31(m,2H),7.29-7.26(m,1H),6.81(d,J=15.0Hz,1H),6.28(dd,J=16.0,7.1Hz,1H),5.87-5.82(m,1H),3.63(d,J=4.6Hz,2H).

[0164] 13 C NMR (100MHz, CDCl3) δ (ppm) 165.6, 135.7, 134.8, 133.4, 129.8, 129.7, 128.7, 128.5, 128.4, 126.8, 123.6, 74.0, 54.3.

[0165] High resolution: Calculated value: [M+Na] + 316.1056, measured value: 316.1066.

[0166] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), tR(major)=7.57min, tR(minor)=9.75min.

[0167] Example 17

[0168] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0169] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 4-methylbenzoic acid IV-3 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-17 with a yield of 73% and an enantioselectivity (ee) of 94%.

[0170]

[0171] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.89 (d, J = 8.3Hz, 2H), 7.32-7.28 (m, 2H), 7.24-7.19 (m, 2H), 7.16 (dd, J = 7.6, 2.1Hz ,3H),6.69(d,J=16.0Hz,1H),6.16(dd,J=16.0,7.0Hz,1H),5.76-5.69(m,1H),3.56-3.45(m,2H),2.31(s,3H).

[0172] 13 C NMR (100MHz, CDCl3) δ (ppm) 165.6, 144.1, 135.8, 134.6, 129.9, 129.2, 128.7, 128.4, 127.0, 126.8, 123.7, 73.8, 54.3, 21.8.

[0173] High resolution: Calculated value: [M+Na] + 330.1213, measured value: 330.1210.

[0174] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 7.59 min, t R (minor) = 9.22 min.

[0175] Example 18

[0176] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0177] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 4-tert-butylbenzoic acid IV-4 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, finally yielding the target product of formula I-18 with a yield of 70% and an enantioselectivity (ee) of 93%.

[0178]

[0179] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.07-8.02 (m, 2H), 7.51-7.47 (m, 2H), 7.41-7.38 (m, 2H), 7.34-7.30 (m, 2H), 7.30-7.2 6(m,1H),6.79(d,J=15.9Hz,1H),6.27(dd,J=15.9,7.0Hz,1H),5.87-5.80(m,1H),3.66-3.58(m,2H),1.35(s,9H).

[0180] 13C NMR (100MHz, CDCl3) δ (ppm) 165.6, 157.1, 135.8, 134.5, 129.7, 128.6, 128.4, 126.9, 126.8, 125.5, 123.7, 73.8, 54.3, 35.2, 31.1.

[0181] High resolution: Calculated value: [M+Na] + 372.1682, measured value: 372.1672.

[0182] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 6.11 min, t R (minor) = 7.15 min.

[0183] Example 19

[0184] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0185] At room temperature, copper tetraacetonitrile hexafluorophosphate catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 4-phenylbenzoic acid IV-5 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-19 with a yield of 68% and an enantioselectivity (ee) of 96%.

[0186]

[0187] 1H NMR (400MHz, CDCl3) δ (ppm) 8.17 (d, J = 8.5Hz, 2H), 7.70 (d, J = 8.4Hz, 2H), 7.65-7.61 (m, 2H), 7.51-7.45 (m, 2H), 7.42 (dd, J = 7.5, 2.1Hz, 3 H),7.37-7.30(m,2H),7.30-7.26(m,1H),6.83(d,J=17.0Hz,1H),6.30(dd,J=15.9,7.1Hz,1H),5.91-5.83(m,1H),3.65(d,J=7.8Hz,2H).

[0188] 13 C NMR (100MHz, CDCl3) δ (ppm) 165.5, 146.1, 139.9, 135.7, 134.8, 130.4, 129.0, 128.7, 128.5, 128.3, 127.3, 127.2, 126.8, 123.6, 74.1, 54.3.

[0189] High resolution: Calculated value: [M+Na] + 392.1369, measured value: 392.1373.

[0190] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (minor) = 13.69min,t R (major) = 31.37 min.

[0191] Example 20

[0192] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0193] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 4-chlorobenzoic acid IV-6 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The resulting product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted sequentially to 100:1, 50:1, 30:1, and 10:1 to obtain the target product of formula I-20 with a yield of 66% and an enantioselectivity (ee) of 95%.

[0194]

[0195] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.03 (d, J = 8.6Hz, 2H), 7.45 (d, J = 8.5Hz, 2H), 7.40 (d, J = 7.1Hz, 2H), 7.35-7.31 (m, 2H), 7 .30-7.27(m,1H),6.80(d,J=15.9Hz,1H),6.26(dd,J=16.0,7.2Hz,1H),5.83(q,J=5.8Hz,1H),3.62(d,J=5.3Hz,2H).

[0196] 13 C NMR (100MHz, CDCl3) δ (ppm) 164.7, 139.8, 135.5, 135.0, 131.2, 128.8, 128.6, 128.5, 128.2, 126.8, 123.2, 74.4, 54.1.

[0197] High resolution: Calculated value: [M+Na] + 350.0667, measured value: 350.068.

[0198] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 9.06 min, t R (minor) = 10.55 min.

[0199] Example 21

[0200] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0201] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 4-bromobenzoic acid IV-7 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted sequentially to 100:1, 50:1, 30:1, and 10:1 to obtain the target product of formula I-21 with a yield of 70% and an enantioselectivity (ee) of 96%.

[0202]

[0203] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.96 (d, J = 8.6 Hz, 2H), 7.61 (d, J = 8.6 Hz, 2H), 7.42-7.38 (m, 2H), 7.36-7.31 (m, 2H), 7.30-7 .27(m,1H),6.80(d,J=15.9Hz,1H),6.26(dd,J=16.0,7.3Hz,1H),5.82(dd,J=13.1,5.8Hz,1H),3.62(d,J=5.8Hz,2H).

[0204] 13 C NMR (100MHz, CDCl3) δ (ppm) 164.8, 135.5, 135.0, 131.8, 131.3, 128.7, 128.6, 128.5, 126.8, 123.2, 74.4, 54.1.

[0205] High resolution: Calculated value: [M+Na] + 394.0162, measured value: 394.0160.

[0206] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 10.27 min, t R (minor) = 11.73 min.

[0207] Example 22

[0208] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0209] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 3-methoxybenzoic acid IV-8 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-22 with a yield of 74% and an enantioselectivity (ee) of 95%.

[0210]

[0211] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.70 (d, J = 7.7Hz, 1H), 7.61 (dd, J = 2.7, 1.5Hz, 1H), 7.39 (dd, J = 7.9, 6.4Hz, 3H), 7.35 (d, J = 5.3Hz, 1H), 7.33-7.28 (m,2H),7.15-7.11(m,1H),6.80(d,J=15.9Hz,1H),6.27(dd,J=16.0,7.1Hz,1H),5.87-5.80(m,1H),3.86(s,3H),3.62(dd,J=5.2,3.6Hz,2H).

[0212] 13C NMR (100MHz, CDCl3) δ (ppm) 165.3, 159.5, 135.5, 134.7, 130.9, 129.4, 128.5, 128.3, 126.7, 123.4, 122.1, 119.9, 113.9, 74.1, 55.4, 54.1.

[0213] High resolution: Calculated value: [M+Na] + 346.1162, measured value: 346.1168.

[0214] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 9.97 min, t R (minor) = 12.48 min.

[0215] Example 23

[0216] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0217] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 3-fluorobenzoic acid IV-9 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-23 with a yield of 61% and an enantioselectivity (ee) of 94%.

[0218]

[0219] 1H NMR (400MHz, CDCl3) δ (ppm) 7.90 (dt, J=7.7, 1.3Hz, 1H), 7.78 (ddd, J=9.3, 2.7, 1.6Hz, 1H), 7.49-7.43 (m, 1H), 7.43-7.40 ( m,2H),7.36-7.27(m,4H),6.81(d,J=15.8Hz,1H),6.26(dd,J=16.0,7.3Hz,1H),5.87-5.81(m,1H),3.63(d,J=5.3Hz,2H).

[0220] 13 C NMR (100MHz, CDCl3) δ (ppm) 164.41 (d, J = 3.0Hz), 162.53 (d, J = 247.3Hz), 135.5, 135.1, 131.86 (d, J = 7.6Hz), 130.13 (d ,J=7.8Hz),128.6,128.5,126.8,125.52(d,J=3.1Hz),123.1,120.40(d,J=21.3Hz),116.67(d,J=23.1Hz),74.5,54.1.

[0221] 19 F NMR(376MHz, CDCl3)δ(ppm)-112.04.

[0222] High resolution: Calculated value: [M+Na] + 334.0962, measured value: 334.0967.

[0223] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 7.57 min, t R (minor) = 10.01 min.

[0224] Example 24

[0225] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0226] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 2-methylbenzoic acid IV-10 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-24 with a yield of 63% and an enantioselectivity (ee) of 94%.

[0227]

[0228] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.00 (d, J = 7.9Hz, 1H), 7.46-7.39 (m, 3H), 7.36-7.31 (m, 2H), 7.30-7.26 (m, 3H), 6.81(d,J=17.0Hz,1H),6.27(dd,J=15.9,7.2Hz,1H),5.85-5.78(m,1H),3.63(d,J=5.9Hz,2H),2.63(s,3H).

[0229] 13 C NMR (100MHz, CDCl3) δ (ppm) 166.3, 140.7, 135.7, 134.7, 132.3, 131.8, 130.7, 129.0, 128.6, 128.4, 126.7, 125.8, 123.7, 73.5, 54.2, 21.8.

[0230] High resolution: Calculated value: [M+Na] + 330.1213, measured value: 330.1210.

[0231] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 6.51 min, t R (minor) = 8.21 min.

[0232] Example 25

[0233] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0234] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 2-chlorobenzoic acid IV-11 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, finally yielding the target product of formula I-25 with a yield of 67% and an enantioselectivity (ee) of 92%.

[0235]

[0236] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.83 (dd, J = 7.8, 1.6Hz, 1H), 7.41-7.36 (m, 2H), 7.36-7.32 (m, 2H), 7.32-7.26 (m, 2H), 7.24-7.22 ( m,1H),7.19(d,J=8.1Hz,1H),6.77(d,J=15.9Hz,1H),6.19(dd,J=15.9,7.3Hz,1H),5.79-5.71(m,1H),3.57(d,J=4.8Hz,2H).

[0237] 13 C NMR (100MHz, CDCl3) δ (ppm) 164.6, 135.6, 135.3, 134.0, 132.9, 131.6, 131.3, 129.6, 128.9, 128.5, 126.8, 126.7, 123.2, 74.5, 54.1.

[0238] High resolution: Calculated value: [M+Na] + 350.0667, Measured value: 350.0666.

[0239] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 9.14 min, t R (minor) = 12.42 min.

[0240] Example 26

[0241] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0242] At room temperature, copper tetraacetonitrile hexafluorophosphate catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and piperic acid IV-12 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-26 with a yield of 58% and an enantioselectivity (ee) of 98%.

[0243]

[0244] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.72 (dd, J = 8.3, 1.7Hz, 1H), 7.52 (d, J = 1.7Hz, 1H), 7.42-7.37 (m, 2H), 7.35-7.30 (m, 2H), 7.29-7.26 (m, 1H),6.86(d,J=8.2Hz,1H),6.78(d,J=15.9Hz,1H),6.25(dd,J=16.0,7.1Hz,1H),6.05(s,2H),5.83-5.78(m,1H),3.65-3.53(m,2H).

[0245] 13C NMR (100MHz, CDCl3) δ (ppm) 164.9, 152.0, 147.8, 135.7, 134.7, 128.7, 128.4, 126.8, 125.8, 123.9, 123.6, 109.7, 108.1, 101.9, 73.9, 54.2.

[0246] High resolution: Calculated value: [M+Na] + 360.0955, Measured value: 360.0950

[0247] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), tR(minor)=10.38min, tR(major)=12.73min.

[0248] Example 27

[0249] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0250] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 2-chloro-4-fluorobenzoic acid IV-13 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen conditions. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-27 with a yield of 61% and an enantioselectivity (ee) of 92%.

[0251]

[0252] 1H NMR (400MHz, CDCl3) δ (ppm) 7.99-7.92 (m, 1H), 7.43-7.39 (m, 2H), 7.36-7.31 (m, 2H), 7.30-7.27 (m, 1H), 7.2 5-7.19(m,2H),6.82(d,J=15.9Hz,1H),6.24(dd,J=16.0,7.3Hz,1H),5.87-5.79(m,1H),3.66-3.58(m,2H).

[0253] 13 C NMR (100MHz, CDCl3) δ (ppm) 162.5 (d, J = 4.1Hz), 161.96 (d, J = 264.6Hz), 140.4 (d, J = 10.3Hz), 135.5, 135.2, 133.1 ( d,J=1.6Hz),128.6,128.5,126.8,124.7(d,J=3.9Hz),123.0,117.9(d,J=25.8Hz),116.9(d,J=9.6Hz),74.5,54.0.

[0254] 19 F NMR(376MHz, CDCl3)δ(ppm)-105.77.

[0255] High resolution: Calculated value: [M+Na] + 368.0573, measured value: 368.0567.

[0256] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 9.38 min, t R (minor) = 11.07 min.

[0257] Example 28

[0258] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0259] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 2-furanic acid IV-14 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-28 with a yield of 64% and an enantioselectivity (ee) of 95%.

[0260]

[0261] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.62 (dd, J=1.8, 0.8Hz, 1H), 7.43-7.38 (m, 2H), 7.33 (t, J=7.2Hz, 2H), 7.30-7.25 (m, 2H), 6.8 0(d,J=15.9Hz,1H),6.54(dd,J=3.5,1.7Hz,1H),6.25(dd,J=16.0,7.3Hz,1H),5.85-5.75(m,1H),3.60(d,J=5.3Hz,2H).

[0262] 13 C NMR (100MHz, CDCl3) δ (ppm) 157.5, 146.8, 144.1, 135.6, 135.2, 128.6, 128.5, 126.8, 123.1, 118.7, 112.0, 74.0, 54.0.

[0263] High resolution: Calculated value: [M+Na] + 306.0849, measured value: 306.0857.

[0264] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (minor) = 8.13min,t R(major) = 10.27 min.

[0265] Example 29

[0266] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0267] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and 5-methylthiophenecarboxylic acid IV-15 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-29 with a yield of 63% and an enantioselectivity (ee) of 89%.

[0268]

[0269] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.69 (d, J = 3.7Hz, 1H), 7.43-7.37 (m, 2H), 7.36-7.29 (m, 2H), 7.29-7.25 (m, 1H ),6.83-6.74(m,2H),6.24(dd,J=16.0,7.1Hz,1H),5.81-5.71(m,1H),3.57(d,J=4.8Hz,2H),2.53(s,3H).

[0270] 13 C NMR (100MHz, CDCl3) δ (ppm) 161.1, 148.8, 135.7, 134.7, 134.5, 130.4, 128.6, 128.4, 126.8, 126.5, 123.5, 74.0, 54.1, 15.8.

[0271] High resolution: Calculated value: [M+Na] + 336.0777, Measured value: 336.0775.

[0272] HPLC: (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ=254nm, 25℃), t R (major) = 8.42 min, t R (minor) = 10.07 min.

[0273] Example 30

[0274] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0275] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and phenylpropynic acid IV-16 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until TLC detection showed complete reaction. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-30 in 55% yield with an enantioselectivity (ee) of 94%.

[0276]

[0277] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.69-7.61 (m, 2H), 7.53-7.48 (m, 1H), 7.47-7.42 (m, 4H), 7.42-7.36 (m, 3H), 7.3 6-7.33(m,1H),6.84(d,J=15.9Hz,1H),6.24(dd,J=15.9,7.5Hz,1H),5.76-5.71(m,1H),3.69-3.58(m,2H).

[0278] 13C NMR (100MHz, CDCl3) δ (ppm) 152.9, 135.6, 135.5, 133.1, 130.8, 128.7, 128.6, 128.6, 128.5, 126.8, 126.7, 122.6, 119.4, 87.4, 80.2, 74.9, 53.7.

[0279] High resolution: Calculated value: [M+Na] + 340.1056, measured value: 340.1053.

[0280] HPLC: analysis (Chiralpak AD column, hexane / i-PrOH, 95:5v / v, flow rate 1.0mL / min, λ = 254nm, 25℃), t R (minor) = 11.39min,t R (major) = 18.44 min.

[0281] Example 31

[0282] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0283] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and probenecid IV-17 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to obtain the target product of formula I-31 of this invention, with a yield of 43% and an enantioselectivity (ee) of 96%.

[0284]

[0285] 1H NMR (400MHz, CDCl3) δ (ppm) 8.21 (d, J = 8.5Hz, 2H), 7.90 (d, J = 8.4Hz, 2H), 7.41 (d, J = 6.6Hz, 2H), 7.33 (t, J = 7.2Hz, 2H), 7.31-7.26 (m, 1H), 6.82 (d, J = 15.9Hz,1H),6.26(dd,J=16.0,7.4Hz,1H),5.88-5.81(m,1H),3.65(d,J=5 .2Hz,2H),3.14-3.06(m,4H),1.55(q,J=7.6Hz,4H),0.87(t,J=7.4Hz,6H).

[0286] 13 C NMR (100MHz, CDCl3) δ (ppm) 164.2, 144.6, 135.5, 135.4, 133.0, 130.4, 128.7, 128.6, 127.1, 126.8, 122.9, 74.8, 54.1, 49.9, 21.9, 11.1.

[0287] High resolution: Calculated value: [M+Na] + :479.1723, measured value: 479.1730.

[0288] HPLC: analysis (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ = 254nm, 25℃), t R (minor) = 20.67min,t R (major) = 45.17 min.

[0289] Example 32

[0290] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0291] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and atalulin IV-18 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm UV irradiation at room temperature until TLC detection showed complete reaction. The resulting product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted sequentially to 100:1, 50:1, 30:1, and 10:1 to obtain the target product of formula I-32 with a yield of 52% and an enantioselectivity (ee) of 96%.

[0292]

[0293] 1 H NMR (400MHz, CDCl3) δ (ppm) 8.82 (d, J = 1.9Hz, 1H), 8.32 (d, J = 7.7Hz, 1H), 8.22-8.10 (m, 2H), 7.58-7.51 (m, 2H), 7.33 (d, J = 7.0 Hz,2H),7.24-7.16(m,5H),6.75(d,J=15.9Hz,1H),6.21(dd,J=15.9,7.3Hz,1H),5.80(q,J=6.0Hz,1H),3.58(d,J=5.4Hz,2H).

[0294] 13 C NMR (100MHz, CDCl3) δ (ppm) 173,1 (d, J = 4.3Hz), 167.9, 164.8, 160.8 (d, J = 260.8Hz), 145.4, 135.6, 135.1, 134.7 (d, J = 8.7Hz), 132.4, 132.1, 13 1.0,130.6,129.4,129.2,128.9,128.6,128.5,127.3,126.8,124.7(d, J=3.8Hz), 123.3, 117.2 (d, J=20.8Hz), 112.6 (d, J=11.3Hz), 74.5, 54.1.

[0295] 19 F NMR(376MHz, CDCl3)δ(ppm)-108.13.

[0296] High resolution: Calculated value: [M+Na] + :478.1286, measured value: 478.1294.

[0297] HPLC: analysis (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ = 254nm, 25℃), t R (major) = 19.09 min, t R (minor) = 32.11 min.

[0298] Example 33

[0299] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0300] At room temperature, copper tetraacetonitrile metal catalyst (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 min under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and adapalene IV-19 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out under 390 nm UV irradiation at room temperature until TLC detection showed complete reaction. The resulting product was separated by silica gel column chromatography. The ratio of petroleum ether to ethyl acetate in the eluent was adjusted sequentially to 100:1, 50:1, 30:1, and 10:1 to obtain the target product of formula I-33 in 60% yield with an enantioselectivity (ee) of 95%.

[0301]

[0302] 1H NMR (400MHz, CDCl3) δ (ppm) 8.68 (s, 1H), 8.12 (d, J = 6.9Hz, 1H), 8.01 (d, J = 9.0Hz, 2H), 7.95 (d, J = 8.4Hz, 1H), 7.8 1(dd,J=8.5,1.8Hz,1H),7.61(d,J=2.3Hz,1H),7.56(dd,J=8.4,2.2Hz,1H),7.43(d,J=7.3Hz,2H),7.34(t,J=7. 4Hz,3H),7.29(d,J=7.1Hz,1H),7.01(d,J=8.4Hz,1H),6.86(d,J=16.0Hz,1H),6.34(dd,J=16.1,7.1Hz,1H),5.9 2(q,J=5.8Hz,1H),3.91(s,3H),3.69(d,J=5.2Hz,2H),2.19(d,J=2.9Hz,6H),2.11(s,3H),1.81(d,J=3.0Hz,6H).

[0303] 13 C NMR (100MHz, CDCl3) δ (ppm) 165.7,158.9,141.6,139.0,136.1,135.7,134.8,132.5,131.2,131.2,129.8,128.6,128 .4,128.3,126.8,126.6,126.4,126.0,125.7,125.6,124.7,123.7,112.1,74.1,55.2,54.3,40.6,37.1,29.1,26.9.

[0304] High resolution: Calculated value: [M+Na] + :606.2727, Measured value: 606.2731.

[0305] HPLC: analysis (Chiralpak OD column, hexane / i-PrOH, 95:5v / v, flow rate 0.5mL / min, λ = 254nm, 25℃), t R (major) = 31.36 min, t R (minor) = 37.33 min.

[0306] Example 34

[0307] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0308] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and bicyclo[1.1.1]pentane (BCP) dicarboxylic acid monomethyl ester IV-20 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-34 with a yield of 28% and an enantioselectivity (ee) of 97%.

[0309]

[0310] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.43-7.27 (m, 5H), 6.69 (d, J = 15.9Hz, 1H), 6.14 (dd, J = 16.0 ,7.3Hz,1H),5.62-5.57(m,1H),3.69(d,J=1.2Hz,3H),3.52-3.41(qm,2H),2.37(s,6H).

[0311] 13 C NMR (100MHz, CDCl3) δ (ppm) 169.6, 168.2, 135.5, 135.0, 128.7, 128.5, 126.8, 123.2, 74.4, 53.8, 52.9, 51.9, 37.7, 37.7.

[0312] High resolution: Calculated value: [M+Na] + 364.1268, Measured value: 364.1269.

[0313] HPLC: analysis (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ = 254nm, 25℃), t R (major) = 10.95 min, t R (minor) = 14.27 min.

[0314] Example 35

[0315] This embodiment provides a method for preparing an alkyl azide chiral allyl ester compound, comprising the following steps:

[0316] At room temperature, copper hexafluorophosphate tetraacetonitrile (0.002 mmol, 2 mol%) and ligand L (0.0024 mmol, 2.4 mol%) were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Then, phenyl-substituted 1,3-diene II-1 (0.3 mmol, 3.0 equiv.), azidobenzyldiazolone (Ts-ABZ) reagent III (0.2 mmol, 2.0 equiv.), and bicyclo[2.2.2]octanedicarboxylic acid monomethyl ester IV-21 (0.1 mmol, 1.0 equiv.) were added, and the mixture was degassed three times under liquid nitrogen. The reaction was then carried out at room temperature under 390 nm ultraviolet light until TLC detection showed complete reaction. The product obtained was separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the order of 100:1, 50:1, 30:1, and 10:1, respectively, to finally obtain the target product of formula I-35 with a yield of 28% and an enantioselectivity (ee) of 97%.

[0317]

[0318] 1 H NMR (400MHz, CDCl3) δ (ppm) 7.34-7.29 (m, 2H), 7.29-7.23 (m, 2H), 7.23-7.20 (m, 1H), 6.60 (d, J = 16.0Hz, 1H ),6.05(dd,J=16.0,7.0Hz,1H),5.49(q,J=6.0Hz,1H),3.58(s,3H),3.46-3.34(m,2H),1.82-1.74(m,12H).

[0319] 13 C NMR (100MHz, CDCl3) δ (ppm) 177.8, 176.3, 135.6, 134.3, 128.6, 128.4, 126.7, 123.6, 73.2, 54.1, 51.8, 38.9, 38.6, 27.7, 27.7.

[0320] High resolution: Calculated value: [M+Na] + :406.1737, Measured value: 406.1745.

[0321] HPLC: analysis (Chiralpak OD column, hexane / i-PrOH, 90:10v / v, flow rate 1.0mL / min, λ = 254nm, 25℃), t R (major) = 10.77 min, t R (minor) = 14.55 min.

[0322] The above detailed embodiments describe the implementation of the present invention; however, the present invention is not limited to the specific details of the above embodiments. Within the scope of the claims and technical concept of the present invention, various simple modifications and changes can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. A method for preparing an alkyl azide chiral allyl ester compound, characterized in that, It has the following general structural formula: ； Formula I R 1 Selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazolyl; R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, bicyclo[1.1.1]pentanecarboxylate methyl ester and bicyclo[2.2.2]octanecarboxylate methyl ester or benzoyl ester; The alkyl-substituted phenyl group is selected from any one of 4-methylphenyl, 4-tert-butylphenyl, 3-methylphenyl or 2-methylphenyl; the aromatic-substituted phenyl group is 4-phenylphenyl. The preparation method of the alkyl azide chiral allyl ester compound includes the following steps: The catalyst and benzofuran oxazoline ligand were dissolved in an organic solvent and stirred under inert gas protection to obtain mixture I; Diene, high-valent iodine azide reagent and carboxylic acid are added to the mixture I and degassed to obtain mixture II; Mixture II was placed under ultraviolet light for further reaction, and the alkyl azide chiral allyl ester compound was isolated. The general structural formula of the diene is as follows: R 1 Selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazolyl; The general structural formula of the carboxylic acid is R. 2 -CO2H, R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, bicyclo[1.1.1]pentanecarboxylate methyl ester and bicyclo[2.2.2]octanecarboxylate methyl ester or benzoyl ester; The high-valent iodine azide reagent is a benzyldiazolone azide reagent, with the following structural formula: In NTs, N represents nitrogen and Ts represents p-toluenesulfonyl group; The catalyst is copper tetraacetonitrile hexafluorophosphate; The benzofuranoxazolin ligand is: 。 2. The method for preparing the alkyl azide chiral allyl ester compound according to claim 1, characterized in that, The halophenyl group is selected from any one of 2-fluorophenyl, 2-chlorophenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 4-chlorophenyl, or 4-bromophenyl.

3. The method for preparing the alkyl azide chiral allyl ester compound according to claim 1, characterized in that, The reaction formula for synthesizing the alkyl azide chiral allyl ester compound is as follows: ， R 1 Selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, naphthyl or thiazolyl; R 2 It is selected from any one of phenyl, alkyl-substituted phenyl, methoxyphenyl, aromatic-substituted phenyl, halophenyl, piperidine, furanyl, 2-(5-methyl)thiophene, phenylethynyl, bicyclo[1.1.1]pentanecarboxylate methyl ester and bicyclo[2.2.2]octanecarboxylate methyl ester or benzoyl ester.

4. A method for preparing an alkyl azide chiral allyl ester compound, characterized in that, Includes the following steps: At room temperature, 0.002 mmol of copper tetraacetonitrile metal catalyst and 0.0024 mmol of ligand L were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Add 0.3 mmol of phenyl-substituted 1,3-diene, 0.2 mmol of azidobenzyldiazolone reagent and 0.1 mmol of probenecid, and degas three times under liquid nitrogen conditions; The reaction was carried out under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The products obtained were separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to finally obtain the target product. ; The ligand L is: ； The structural formula of the azidobenzyldiazolone reagent is: ； In NTs, N represents nitrogen and Ts represents p-toluenesulfonyl group.

5. A method for preparing an alkyl azide chiral allyl ester compound, characterized in that, Includes the following steps: At room temperature, 0.002 mmol of copper tetraacetonitrile metal catalyst and 0.0024 mmol of ligand L were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Add 0.3 mmol of phenyl-substituted 1,3-diene, 0.2 mmol of azidobenzyldiazolone reagent and 0.1 mmol of atalulone, and degas three times under liquid nitrogen conditions; The reaction was carried out under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The products obtained were separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to finally obtain the target product. ; The ligand L is: ； The structural formula of the azidobenzyldiazolone reagent is: ； In NTs, N represents nitrogen and Ts represents p-toluenesulfonyl group.

6. A method for preparing an alkyl azide chiral allyl ester compound, characterized in that, Includes the following steps: At room temperature, 0.002 mmol of copper tetraacetonitrile metal catalyst and 0.0024 mmol of ligand L were dissolved in 2 mL of dichloromethane and stirred for 30 minutes under argon protection. Add 0.3 mmol of phenyl-substituted 1,3-diene, 0.2 mmol of azidobenzyldiazolone reagent and 0.1 mmol of adapalene, and degas three times under liquid nitrogen conditions; The reaction was carried out under 390 nm ultraviolet light at room temperature until the reaction was complete as detected by TLC. The products obtained were separated by silica gel column chromatography. In the eluent, the ratio of petroleum ether to ethyl acetate was adjusted in the following order: 100:1, 50:1, 30:1, and 10:1, to finally obtain the target product. ； The ligand L is: ； The structural formula of the azidobenzyldiazolone reagent is: ； In NTs, N represents nitrogen and Ts represents p-toluenesulfonyl group.

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