Ligand for preparing alpha chiral aryl ketone, preparation method of ligand and synthesis method of alpha chiral aryl ketone

Abstract

The invention relates to a synthesis method of alpha chiral aryl ketone, and belongs to the technical field of chemical synthesis. The method comprises the following step: reacting a compound a, a compound b and a compound c in the presence of a catalyst, a ligand, alkali, silane and a solvent to obtain a compound d. The method has the advantages of high yield, high ee value and excellent technical effect.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of chemical synthesis, and particularly relates to a ligand for preparing alpha-chiral aryl ketone and a preparation method thereof and a synthesis method of alpha-chiral aryl ketone. BACKGROUND

[0002] Chiral alpha-aryl ketone is an important molecular skeleton, and is widely present in high-value target molecules and is also a precursor for efficiently synthesizing other functional groups. Chiral alpha-aryl ketone is widely present in active and functional molecules such as natural products, drug molecules, pesticide molecules, fragrances and materials. Meanwhile, chiral alpha-aryl ketone is also an important synthetic precursor for synthesizing other chiral fragments and skeletons in the organic synthesis and pharmaceutical industries.

[0003] In recent years, developing an efficient synthesis method for catalytically constructing chiral alpha-aryl ketone compounds has become one of the research hotspots in the field of organic synthesis. However, the existing synthesis method still has problems such as low yield, low enantiomeric selectivity, complex operation, low safety and high cost. SUMMARY

[0004] The application develops a new reaction mode for directly obtaining chiral alpha-arylated dialkyl ketone from two olefins and one carbonyl substitute. An aliphatic olefin and a styrene are used as two different alkyl precursors, and the chemical selectivity, regioselectivity and enantiomeric selectivity are controlled. Two different olefins are connected together through a regioselective and enantioselective carbonylation reaction. The selection of the olefin can well control the nickel-catalyzed carbonylation reaction of different olefins, and an asymmetric alpha-arylated asymmetric dialkyl ketone can be directly synthesized from two different olefins, which represents a new reaction mode.

[0005] In a first aspect, the application provides a synthesis method of compound d. The synthesis method of compound d comprises:

[0006]

[0007] The compound a, the compound b and the compound c react in the presence of a catalyst, a ligand, a base, a silane and a solvent in the presence of nitrogen or an inert gas atmosphere to obtain the compound d;

[0008] Ar is selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

[0009] R 1 selected from hydrogen, substituted or unsubstituted C6-C 12 aryl (for example, substituted or unsubstituted C6 aryl, substituted or unsubstituted C7 aryl, substituted or unsubstituted C8 aryl, substituted or unsubstituted C9 aryl, substituted or unsubstituted C 10aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl (e.g., substituted or unsubstituted C4heteroaryl, substituted or unsubstituted C5heteroaryl, substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C1-C 10 straight-chain alkyl (e.g., substituted or unsubstituted C1straight-chain alkyl, substituted or unsubstituted C2straight-chain alkyl, substituted or unsubstituted C3straight-chain alkyl, substituted or unsubstituted C4straight-chain alkyl, substituted or unsubstituted C5straight-chain alkyl, substituted or unsubstituted C6straight-chain alkyl, substituted or unsubstituted C7straight-chain alkyl, substituted or unsubstituted C8straight-chain alkyl, substituted or unsubstituted C9straight-chain alkyl, substituted or unsubstituted C 10 straight-chain alkyl, substituted or unsubstituted C3-C 10 branched-chain alkyl (e.g., substituted or unsubstituted C3branched-chain alkyl, substituted or unsubstituted C4branched-chain alkyl, substituted or unsubstituted C5branched-chain alkyl, substituted or unsubstituted C6branched-chain alkyl, substituted or unsubstituted C7branched-chain alkyl, substituted or unsubstituted C8branched-chain alkyl, substituted or unsubstituted C9branched-chain alkyl, substituted or unsubstituted C 10 branched-chain alkyl, substituted or unsubstituted C3-C 10 cycloalkyl (e.g., substituted or unsubstituted C3cycloalkyl, substituted or unsubstituted C4cycloalkyl, substituted or unsubstituted C5cycloalkyl, substituted or unsubstituted C6cycloalkyl, substituted or unsubstituted C7cycloalkyl, substituted or unsubstituted C8cycloalkyl, substituted or unsubstituted C9cycloalkyl, substituted or unsubstituted C 10 cycloalkyl);

[0010] R 8 is selected from the group consisting of n-propyl, methyl, ethyl, i-propyl, sec-butyl, phenyl, benzyl, n-butyl, n-pentyl, i-butyl, sec-butyl, cyclopentyl, n-hexyl, n-heptyl, n-decyl;

[0011] R 2 , R 3 , R 4 is selected from one of the following groups:

[0012] (1) R 3 is selected from the group consisting of hydrogen, substituted or unsubstituted C6-C 12Aryl groups (e.g., substituted or unsubstituted C6 aryl, substituted or unsubstituted C7 aryl, substituted or unsubstituted C8 aryl, substituted or unsubstituted C9 aryl, substituted or unsubstituted C...) 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C4-C 12 Heteroaryl groups (e.g., substituted or unsubstituted C4 heteroaryl, substituted or unsubstituted C5 heteroaryl, substituted or unsubstituted C6 heteroaryl, substituted or unsubstituted C7 heteroaryl, substituted or unsubstituted C8 heteroaryl, substituted or unsubstituted C9 heteroaryl, substituted or unsubstituted C...) 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 (heteroaryl), substituted or unsubstituted C1-C 10 Straight-chain alkyl groups (e.g., substituted or unsubstituted C1 straight-chain alkyl groups, substituted or unsubstituted C2 straight-chain alkyl groups, substituted or unsubstituted C3 straight-chain alkyl groups, substituted or unsubstituted C4 straight-chain alkyl groups, substituted or unsubstituted C5 straight-chain alkyl groups, substituted or unsubstituted C6 straight-chain alkyl groups, substituted or unsubstituted C7 straight-chain alkyl groups, substituted or unsubstituted C8 straight-chain alkyl groups, substituted or unsubstituted C9 straight-chain alkyl groups, substituted or unsubstituted C... 10 Straight-chain alkyl), substituted or unsubstituted C3-C 10 Branched alkyl groups (e.g., substituted or unsubstituted C3 branched alkyl groups, substituted or unsubstituted C4 branched alkyl groups, substituted or unsubstituted C5 branched alkyl groups, substituted or unsubstituted C6 branched alkyl groups, substituted or unsubstituted C7 branched alkyl groups, substituted or unsubstituted C8 branched alkyl groups, substituted or unsubstituted C9 branched alkyl groups, substituted or unsubstituted C4 branched alkyl groups, substituted or unsubstituted C5 branched alkyl groups, substituted or unsubstituted C6 ... 10 Branched alkyl groups, substituted or unsubstituted C3-C 10 Cycloalkyl groups (e.g., substituted or unsubstituted C3 cycloalkyl, substituted or unsubstituted C4 cycloalkyl, substituted or unsubstituted C5 cycloalkyl, substituted or unsubstituted C6 cycloalkyl, substituted or unsubstituted C7 cycloalkyl, substituted or unsubstituted C8 cycloalkyl, substituted or unsubstituted C9 cycloalkyl, substituted or unsubstituted C...) 10 cycloalkyl);

[0013] R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclic group; wherein, in compound c, the R 2 R 4 and R 2 R4 each adjacent carbon atom together form a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclyl ring that contains only one alkenyl and no alkynyl within the ring; 2 , R 4 and R 2 , R 4 each adjacent carbon atom together form a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclyl ring that contains only one alkenyl and no alkynyl within the ring;

[0014] (2) R 3 and R 4 are hydrogen;

[0015] R 2 is substituted or unsubstituted C6-C 12 aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C3-C 12 heteroaryl (e.g., substituted or unsubstituted C3heteroaryl, substituted or unsubstituted C4heteroaryl, substituted or unsubstituted C5heteroaryl, substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl), substituted or unsubstituted C1-C 10 linear alkyl (e.g., substituted or unsubstituted C1linear alkyl, substituted or unsubstituted C2linear alkyl, substituted or unsubstituted C3linear alkyl, substituted or unsubstituted C4linear alkyl, substituted or unsubstituted C5linear alkyl, substituted or unsubstituted C6linear alkyl, substituted or unsubstituted C7linear alkyl, substituted or unsubstituted C8linear alkyl, substituted or unsubstituted C9linear alkyl, substituted or unsubstituted C 10 linear alkyl), substituted or unsubstituted C3-C 10 branched alkyl (e.g., substituted or unsubstituted C3branched alkyl, substituted or unsubstituted C4branched alkyl, substituted or unsubstituted C5branched alkyl, substituted or unsubstituted C6branched alkyl, substituted or unsubstituted C7branched alkyl, substituted or unsubstituted C8branched alkyl, substituted or unsubstituted C9branched alkyl, substituted or unsubstituted C 10 branched alkyl), substituted or unsubstituted C3-C10 cycloalkyl (e.g., substituted or unsubstituted C3cycloalkyl, substituted or unsubstituted C4cycloalkyl, substituted or unsubstituted C5cycloalkyl, substituted or unsubstituted C6cycloalkyl, substituted or unsubstituted C7cycloalkyl, substituted or unsubstituted C8cycloalkyl, substituted or unsubstituted C9cycloalkyl, substituted or unsubstituted C 10 heterocycloalkyl (e.g., substituted or unsubstituted 3-membered heterocycloalkyl, substituted or unsubstituted 4-membered heterocycloalkyl, substituted or unsubstituted 5-membered heterocycloalkyl, substituted or unsubstituted 6-membered heterocycloalkyl, substituted or unsubstituted 7-membered heterocycloalkyl, substituted or unsubstituted 8-membered heterocycloalkyl, substituted or unsubstituted 9-membered heterocycloalkyl, substituted or unsubstituted 10-membered heterocycloalkyl), substituted or unsubstituted 3- to 10-membered heterocycloalkyl (e.g., substituted or unsubstituted 3-membered heterocycloalkyl, substituted or unsubstituted 4-membered heterocycloalkyl, substituted or unsubstituted 5-membered heterocycloalkyl, substituted or unsubstituted 6-membered heterocycloalkyl, substituted or unsubstituted 7-membered heterocycloalkyl, substituted or unsubstituted 8-membered heterocycloalkyl, substituted or unsubstituted 9-membered heterocycloalkyl, substituted or unsubstituted 10-membered heterocycloalkyl);

[0016] (3) R 4 is hydrogen;

[0017] R 2 , R 3 , and R 2 , R 3 each adjacent carbon atom together form substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered cycloalkyl, substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered bridged heterocycloalkyl, substituted or unsubstituted C6-C20aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl, substituted or unsubstituted C 13 aryl, substituted or unsubstituted C 14 aryl, substituted or unsubstituted C 15 aryl, substituted or unsubstituted C 16 aryl, substituted or unsubstituted C 17 aryl, substituted or unsubstituted C 18 aryl, substituted or unsubstituted C 19 aryl, substituted or unsubstituted C 20 aryl), substituted or unsubstituted C6-C 20Heteroaryl groups (e.g., substituted or unsubstituted C6 heteroaryl, substituted or unsubstituted C7 heteroaryl, substituted or unsubstituted C8 heteroaryl, substituted or unsubstituted C9 heteroaryl, substituted or unsubstituted C...) 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C 13 heteroaryl, substituted or unsubstituted C 14 heteroaryl, substituted or unsubstituted C 15 heteroaryl, substituted or unsubstituted C 16 heteroaryl, substituted or unsubstituted C 17 heteroaryl, substituted or unsubstituted C 18 heteroaryl, substituted or unsubstituted C 19 heteroaryl, substituted or unsubstituted C 20 (Heteroary aryl);

[0018] (4)R 4 It is hydrogen;

[0019] R 2 and R 3 Each C6-C is independently selected from substituted or unsubstituted C6-C. 20 Aryl groups (e.g., substituted or unsubstituted C6 aryl, substituted or unsubstituted C7 aryl, substituted or unsubstituted C8 aryl, substituted or unsubstituted C9 aryl, substituted or unsubstituted C...) 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl, substituted or unsubstituted C 13 aryl, substituted or unsubstituted C 14 aryl, substituted or unsubstituted C 15 aryl, substituted or unsubstituted C 16 aryl, substituted or unsubstituted C 17 aryl, substituted or unsubstituted C 18 aryl, substituted or unsubstituted C 19 aryl, substituted or unsubstituted C 20 aryl), substituted or unsubstituted C4-C 20 Heteroaryl groups (e.g., substituted or unsubstituted C4 heteroaryl, substituted or unsubstituted C5 heteroaryl, substituted or unsubstituted C6 heteroaryl, substituted or unsubstituted C7 heteroaryl, substituted or unsubstituted C8 heteroaryl, substituted or unsubstituted C9 heteroaryl, substituted or unsubstituted C...) 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C 13heteroaryl, substituted or unsubstituted C 14 heteroaryl, substituted or unsubstituted C 15 heteroaryl, substituted or unsubstituted C 16 heteroaryl, substituted or unsubstituted C 17 heteroaryl, substituted or unsubstituted C 18 heteroaryl, substituted or unsubstituted C 19 heteroaryl, substituted or unsubstituted C 20 heteroaryl, substituted or unsubstituted C1-C 10 straight-chain alkyl (e.g., substituted or unsubstituted C1straight-chain alkyl, substituted or unsubstituted C2straight-chain alkyl, substituted or unsubstituted C3straight-chain alkyl, substituted or unsubstituted C4straight-chain alkyl, substituted or unsubstituted C5straight-chain alkyl, substituted or unsubstituted C6straight-chain alkyl, substituted or unsubstituted C7straight-chain alkyl, substituted or unsubstituted C8straight-chain alkyl, substituted or unsubstituted C9straight-chain alkyl, substituted or unsubstituted C 10 straight-chain alkyl), substituted or unsubstituted C3-C 10 branched-chain alkyl (e.g., substituted or unsubstituted C3branched-chain alkyl, substituted or unsubstituted C4branched-chain alkyl, substituted or unsubstituted C5branched-chain alkyl, substituted or unsubstituted C6branched-chain alkyl, substituted or unsubstituted C7branched-chain alkyl, substituted or unsubstituted C8branched-chain alkyl, substituted or unsubstituted C9branched-chain alkyl, substituted or unsubstituted C 10 branched-chain alkyl), substituted or unsubstituted C3-C 10 cycloalkyl (e.g., substituted or unsubstituted C3cycloalkyl, substituted or unsubstituted C4cycloalkyl, substituted or unsubstituted C5cycloalkyl, substituted or unsubstituted C6cycloalkyl, substituted or unsubstituted C7cycloalkyl, substituted or unsubstituted C8cycloalkyl, substituted or unsubstituted C9cycloalkyl, substituted or unsubstituted C 10 cycloalkyl), substituted or unsubstituted 3- to 10-membered heterocycloalkyl (e.g., substituted or unsubstituted 3-membered heterocycloalkyl, substituted or unsubstituted 4-membered heterocycloalkyl, substituted or unsubstituted 5-membered heterocycloalkyl, substituted or unsubstituted 6-membered heterocycloalkyl, substituted or unsubstituted 7-membered heterocycloalkyl, substituted or unsubstituted 8-membered heterocycloalkyl, substituted or unsubstituted 9-membered heterocycloalkyl, substituted or unsubstituted 10-membered heterocycloalkyl).

[0020] In some embodiments, the ligand is an S-configuration ligand, the compound d is or the ligand is an R-configuration ligand; the compound d is

[0021] In some embodiments, the inert gas comprises at least one of helium, neon, argon, krypton, xenon.

[0022] In some embodiments, the catalyst is selected from a nickel catalyst.

[0023] In some embodiments, the catalyst is selected from at least one of NiI2, NiBr2, NiCl2, NiBr2DME, NiCl26H2O, Ni(COD)2, Ni(acac)2, Ni(OTf)2, Ni(OAc)2, and Ni(OAc)24H2O. In some preferred embodiments, the catalyst is selected from at least one of NiBr2, NiCl2, NiCl26H2O, Ni(COD)2, Ni(OAc)2, and Ni(OAc)24H2O. In some more preferred embodiments, the catalyst is selected from at least one of Ni(OAc)2and Ni(OAc)24H2O.

[0024] In some embodiments, the ligand has a structure as shown in compound S4, wherein the configuration of the chiral center marked by “*” is either S configuration or R configuration, and the R 5 , R 6 , R 7 group in the compound S4 is selected from any one of groups ①-④:

[0025] ① the R 5 is selected from H, C1-C10 straight chain alkyl (e.g., substituted or unsubstituted C1 straight chain alkyl, substituted or unsubstituted C2 straight chain alkyl, substituted or unsubstituted C3 straight chain alkyl, substituted or unsubstituted C4 straight chain alkyl, substituted or unsubstituted C5 straight chain alkyl, substituted or unsubstituted C6 straight chain alkyl, substituted or unsubstituted C7 straight chain alkyl, substituted or unsubstituted C8 straight chain alkyl, substituted or unsubstituted C9 straight chain alkyl, substituted or unsubstituted C 10 straight chain alkyl), C3-C10 branched chain alkyl (e.g., substituted or unsubstituted C3 branched chain alkyl, substituted or unsubstituted C4 branched chain alkyl, substituted or unsubstituted C5 branched chain alkyl, substituted or unsubstituted C6 branched chain alkyl, substituted or unsubstituted C7 branched chain alkyl, substituted or unsubstituted C8 branched chain alkyl, substituted or unsubstituted C9 branched chain alkyl, substituted or unsubstituted C 10 branched chain alkyl);

[0026] the R 6 is selected from substituted or unsubstituted C1-C10 straight chain alkyl (e.g., substituted or unsubstituted C1 straight chain alkyl, substituted or unsubstituted C2 straight chain alkyl, substituted or unsubstituted C3 straight chain alkyl, substituted or unsubstituted C4 straight chain alkyl, substituted or unsubstituted C5 straight chain alkyl, substituted or unsubstituted C6 straight chain alkyl, substituted or unsubstituted C7 straight chain alkyl, substituted or unsubstituted C8 straight chain alkyl, substituted or unsubstituted C9 straight chain alkyl, substituted or unsubstituted C10 straight-chain alkyl), substituted or unsubstituted C3-C10 branched-chain alkyl (e.g.: substituted or unsubstituted C3 branched-chain alkyl, substituted or unsubstituted C4 branched-chain alkyl, substituted or unsubstituted C5 branched-chain alkyl, substituted or unsubstituted C6 branched-chain alkyl, substituted or unsubstituted C7 branched-chain alkyl, substituted or unsubstituted C8 branched-chain alkyl, substituted or unsubstituted C9 branched-chain alkyl, substituted or unsubstituted C 10 branched-chain alkyl), substituted or unsubstituted C6-C 12 aryl (e.g.: substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C4-C 12 heteroaryl (e.g.: substituted or unsubstituted C4heteroaryl, substituted or unsubstituted C5heteroaryl, substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl);

[0027] said R 7 is selected from substituted or unsubstituted C6-C 12 aryl (e.g.: substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C4-C 12 heteroaryl (e.g.: substituted or unsubstituted C4heteroaryl, substituted or unsubstituted C5heteroaryl, substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl);

[0028] or 2) said R 5H, C1-C10 straight chain alkyl (e.g., C1 straight chain alkyl, C2 straight chain alkyl, C3 straight chain alkyl, C4 straight chain alkyl, C5 straight chain alkyl, C6 straight chain alkyl, C7 straight chain alkyl, C8 straight chain alkyl, C9 straight chain alkyl, C 10 straight chain alkyl);

[0029] said R 6 is selected from the group consisting of t-butyl, phenyl, benzyl;

[0030] said R 7 is selected from the group consisting of phenyl,

[0031] or 3) said R5and R7, together with the adjacent carbon, form a C6-C 12 aromatic ring (e.g., C6aromatic ring, C7aromatic ring, C8aromatic ring, C9aromatic ring, C 10 aromatic ring, C 11 aromatic ring, C 12 aromatic ring);

[0032] said R6is selected from the group consisting of substituted or unsubstituted C1-C10 straight chain alkyl (e.g., substituted or unsubstituted C1straight chain alkyl, substituted or unsubstituted C2straight chain alkyl, substituted or unsubstituted C3straight chain alkyl, substituted or unsubstituted C4straight chain alkyl, substituted or unsubstituted C5straight chain alkyl, substituted or unsubstituted C6straight chain alkyl, substituted or unsubstituted C7straight chain alkyl, substituted or unsubstituted C8straight chain alkyl, substituted or unsubstituted C9straight chain alkyl, substituted or unsubstituted C 10 straight chain alkyl), substituted or unsubstituted C3-C10 branched chain alkyl (e.g., substituted or unsubstituted C3branched chain alkyl, substituted or unsubstituted C4branched chain alkyl, substituted or unsubstituted C5branched chain alkyl, substituted or unsubstituted C6branched chain alkyl, substituted or unsubstituted C7branched chain alkyl, substituted or unsubstituted C8branched chain alkyl, substituted or unsubstituted C9branched chain alkyl, substituted or unsubstituted C 10 branched chain alkyl), substituted or unsubstituted C6-C 12 aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C4-C 12 heteroaryl (e.g., substituted or unsubstituted C4heteroaryl, substituted or unsubstituted C5heteroaryl, substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C

[0033] or IV said R 5 and R 7 form a phenyl group with the adjacent carbon; said R 6 is a phenyl group.

[0034] In some embodiments, the ligand is selected from at least one of ligand L3, ligand L8, ligand L9, ligand L10, ligand L11, ligand L12, ligand L13, ligand L14, ligand L15, ligand L16, ligand L17, ligand L18, ligand L19, ligand L20, ligand L21, preferably at least one of ligand L12, ligand L13, ligand L14, ligand L15, more preferably at least one of ligand L14, ligand L15,

[0035]

[0036] or the ligand is selected from at least one of ligand (R)-L3, ligand (R)-L8, ligand (R)-L9, ligand (R)-L10, ligand (R)-L11, ligand (R)-L12, ligand (R)-L13, ligand (R)-L14, ligand (R)-L15, ligand (R)-L16, ligand (R)-L17, ligand (R)-L18, ligand (R)-L19, ligand (R)-L20, ligand (R)-L21, preferably at least one of ligand (R)-L12, ligand (R)-L13, ligand (R)-L14, ligand (R)-L15, more preferably at least one of ligand (R)-L14, ligand (R)-L15,

[0037]

[0038] In some embodiments, the base is selected from at least one of Na2CO3, NaHCO3, K2CO3, Cs2CO3. In some preferred embodiments, the base is selected from NaHCO3.

[0039] In some embodiments, the silane is selected from at least one of triethylsilane, diphenylsilane, triethoxysilane, trimethoxysilane, methyldimethoxysilane, methyldiethoxysilane.

[0040] In some embodiments, the solvent is selected from at least one of 2-MeTHF (2-methyltetrahydrofuran), THF (tetrahydrofuran), DME (ethylene glycol dimethyl ether), Dioxane (1,4-dioxane), and DMA (N,N-dimethylacetamide). In some preferred embodiments, the solvent is selected from at least one of 2-MeTHF, THF, DME, and Dioxane. In some more preferred embodiments, the solvent is selected from 2-MeTHF.

[0041] In some embodiments, the reaction temperature is -20°C to 0°C. In some embodiments, the reaction temperature is -20°C, -15°C, -10°C, -5°C, or 0°C. In some embodiments, the reaction temperature is -15°C to -5°C. In some preferred embodiments, the reaction temperature is -10°C.

[0042] In some embodiments, at least one hydrogen atom in Ar, which is substituted as an aryl or heteroaryl group, is independently selected from fluorine, chlorine, bromine, amino, nitro, C1-C6 straight-chain alkyl (e.g., C1-C2-C3-C4-C5-C6), C3-C6 branched alkyl (e.g., C3-C4-C5-C6), C6-C6 branched alkyl (e.g., C3-C4-C5-C6), and C6-C6-C6 branched alkyl groups. 20 Aryl groups (e.g., C6 aryl, C7 aryl, C8 aryl, C9 aryl, C...) 10 Aryl, C 11 Aryl, C 12 Aryl, C 13 Aryl, C 14 Aryl, C 15 Aryl, C 16 Aryl, C 17 Aryl, C 18 Aryl, C 19 Aryl, C 20 Aryl, phenyl), trifluoromethyl, cyano, trimethylsilyl, pivalamido, acetoxy, dimethylamino, methoxy, methylthio, acetyl, methoxycarbonyl, trifluoromethoxy, =O -COOCH3 is replaced.

[0043] In some embodiments, the substituted or unsubstituted aryl group in Ar is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzocyclobutenyl, or substituted or unsubstituted phenyl groups. The substituted or unsubstituted heteroaryl group in Ar is selected from substituted or unsubstituted 1,3-benzodioxonyl or substituted or unsubstituted indolyl.

[0044] In some embodiments, the R 1The substitution in is that it is replaced by at least one benzyloxy group.

[0045] In some embodiments, the R 1 Selected from H, unsubstituted C1-C 10 Straight-chain alkyl groups (e.g., unsubstituted C1 straight-chain alkyl, unsubstituted C2 straight-chain alkyl, unsubstituted C3 straight-chain alkyl, unsubstituted C4 straight-chain alkyl, unsubstituted C5 straight-chain alkyl, unsubstituted C6 straight-chain alkyl, unsubstituted C7 straight-chain alkyl, unsubstituted C8 straight-chain alkyl, unsubstituted C9 straight-chain alkyl, unsubstituted C...) 10 Straight-chain alkyl groups or C1-C groups substituted with at least one OBn group 10 Straight-chain alkyl groups (e.g., C1 straight-chain alkyl groups substituted with at least one OBn group, C2 straight-chain alkyl groups substituted with at least one OBn group, C3 straight-chain alkyl groups substituted with at least one OBn group, C4 straight-chain alkyl groups substituted with at least one OBn group, C5 straight-chain alkyl groups substituted with at least one OBn group, C6 straight-chain alkyl groups substituted with at least one OBn group, C7 straight-chain alkyl groups substituted with at least one OBn group, C8 straight-chain alkyl groups substituted with at least one OBn group, C9 straight-chain alkyl groups substituted with at least one OBn group, or C4 straight-chain alkyl groups substituted with at least one OBn group). 10 (linear alkyl)

[0046] In some embodiments, the R 1 Selected from H, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl or -CH2-OBn.

[0047] In some embodiments, the R 2 R 3 R 4 The definition is selected from one of the following groups:

[0048] (i)R 3 Selected from hydrogen;

[0049] R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9, or 10-membered carbocyclic group; wherein, in compound c, the R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9, or 10-membered carbocyclic group containing only one alkenyl group and no alkynyl group; in compound d, the R 2 R 4 and R2 R 4 each adjacent carbon atom together form a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclyl group that is free of alkenyl and free of alkynyl groups;

[0050] (ii) R 3 and R 4 is hydrogen;

[0051] R 2 is a substituted or unsubstituted C6-C 12 aryl group (e.g., a substituted or unsubstituted C6aryl group, a substituted or unsubstituted C7aryl group, a substituted or unsubstituted C8aryl group, a substituted or unsubstituted C9aryl group, a substituted or unsubstituted C 10 aryl group, a substituted or unsubstituted C 11 aryl group, a substituted or unsubstituted C 12 aryl group), a substituted or unsubstituted C4-C 12 heteroaryl group (e.g., a substituted or unsubstituted C4heteroaryl group, a substituted or unsubstituted C5heteroaryl group, a substituted or unsubstituted C6heteroaryl group, a substituted or unsubstituted C7heteroaryl group, a substituted or unsubstituted C8heteroaryl group, a substituted or unsubstituted C9heteroaryl group, a substituted or unsubstituted C 10 heteroaryl group, a substituted or unsubstituted C 11 heteroaryl group, a substituted or unsubstituted C 12 heteroaryl group), a substituted or unsubstituted C1-C 10 straight-chain alkyl group (e.g., a substituted or unsubstituted C1straight-chain alkyl group, a substituted or unsubstituted C2straight-chain alkyl group, a substituted or unsubstituted C3straight-chain alkyl group, a substituted or unsubstituted C4straight-chain alkyl group, a substituted or unsubstituted C5straight-chain alkyl group, a substituted or unsubstituted C6straight-chain alkyl group, a substituted or unsubstituted C7straight-chain alkyl group, a substituted or unsubstituted C8straight-chain alkyl group, a substituted or unsubstituted C9straight-chain alkyl group, a substituted or unsubstituted C 10 straight-chain alkyl group), a substituted or unsubstituted C3-C 10 branched-chain alkyl group (e.g., a substituted or unsubstituted C3branched-chain alkyl group, a substituted or unsubstituted C4branched-chain alkyl group, a substituted or unsubstituted C5branched-chain alkyl group, a substituted or unsubstituted C6branched-chain alkyl group, a substituted or unsubstituted C7branched-chain alkyl group, a substituted or unsubstituted C8branched-chain alkyl group, a substituted or unsubstituted C9branched-chain alkyl group, a substituted or unsubstituted C 10 branched-chain alkyl group), a substituted or unsubstituted C3-C 10 cycloalkyl group (e.g., a substituted or unsubstituted C3cycloalkyl group, a substituted or unsubstituted C4cycloalkyl group, a substituted or unsubstituted C5cycloalkyl group, a substituted or unsubstituted C6cycloalkyl group, a substituted or unsubstituted C7cycloalkyl group, a substituted or unsubstituted C8cycloalkyl group, a substituted or unsubstituted C9cycloalkyl group, a substituted or unsubstituted C 10cycloalkyl), substituted or unsubstituted C3-C 10 Heterocyclic alkyl groups (e.g., substituted or unsubstituted C3 heterocyclic alkyl groups, substituted or unsubstituted C4 heterocyclic alkyl groups, substituted or unsubstituted C5 heterocyclic alkyl groups, substituted or unsubstituted C6 heterocyclic alkyl groups, substituted or unsubstituted C7 heterocyclic alkyl groups, substituted or unsubstituted C8 heterocyclic alkyl groups, substituted or unsubstituted C9 heterocyclic alkyl groups, substituted or unsubstituted C4 heterocyclic alkyl groups, substituted or unsubstituted C5 heterocyclic alkyl groups, substituted or unsubstituted C6 ... 10 Heterocyclic alkyl groups);

[0052] The R 2 The substitution in is achieved by being replaced by at least one substituent selected from the following: tert-butoxycarbonyl, fluorine, chlorine, bromine, C6-C. 20 Heteroaryl groups (e.g., C6-C7-C8-C9 ... 10 heteroaryl, C 11 heteroaryl, C 12 heteroaryl, C 13 heteroaryl, C 14 heteroaryl, C 15 heteroaryl, C 16 heteroaryl, C 17 heteroaryl, C 18 heteroaryl, C 19 heteroaryl, C 20 (heteroaryl), C6-C 20 Aryl groups (e.g., C6 aryl, C7 aryl, C8 aryl, C9 aryl, C...) 10 Aryl, C 11 Aryl, C 12 Aryl, C 13 Aryl, C 14 Aryl, C 15 Aryl, C 16 Aryl, C 17 Aryl, C 18 Aryl, C 19 Aryl, C 20 Aryl), C3-C 10 Cycloalkyl groups (e.g., C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C...) 10 cycloalkyl), methoxycarbonyl, Benzyloxy, acetyloxy, tert-butyldimethylsiloxy, acetyl, hydroxyl

[0053]

[0054] Or the R 2 The substitution in is achieved by being replaced by at least one substituent selected from the following: tert-butoxycarbonyl, fluorine, chlorine, bromine, phenyl, C3-C 10cycloalkyl (e.g., C3cycloalkyl, C4cycloalkyl, C5cycloalkyl, C6cycloalkyl, C7cycloalkyl, C8cycloalkyl, C9cycloalkyl, C 10 cycloalkyl (e.g., C3cycloalkyl, C4cycloalkyl, C5cycloalkyl, C6cycloalkyl, C7cycloalkyl, C8cycloalkyl, C9cycloalkyl, C benzyloxy, acetyloxy, t-butyldimethylsiloxy, acetyl, hydroxy,

[0055] (iii) R 4 is hydrogen;

[0056] R 2 , R 3 and the carbon atoms adjacent to R 2 , R 3 each together with the carbon atoms adjacent thereto form a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9- or 10-membered cycloalkyl, substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9- or 10-membered bridged cycloalkyl, substituted or unsubstituted C6-C 20 aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl, substituted or unsubstituted C 13 aryl, substituted or unsubstituted C 14 aryl, substituted or unsubstituted C 15 aryl, substituted or unsubstituted C 16 aryl, substituted or unsubstituted C 17 aryl, substituted or unsubstituted C 18 aryl, substituted or unsubstituted C 19 aryl, substituted or unsubstituted C 20 aryl), substituted or unsubstituted C6-C 20 heteroaryl (e.g., substituted or unsubstituted C6heteroaryl, substituted or unsubstituted C7heteroaryl, substituted or unsubstituted C8heteroaryl, substituted or unsubstituted C9heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C 13 heteroaryl, substituted or unsubstituted C 14 heteroaryl, substituted or unsubstituted C 15 heteroaryl, substituted or unsubstituted C 16 heteroaryl, substituted or unsubstituted C 17 heteroaryl, substituted or unsubstituted C 18 heteroaryl, substituted or unsubstituted C19 heteroaryl, substituted or unsubstituted C 20 heteroaryl);

[0057] substituted or unsubstituted C6-C 20 aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl, substituted or unsubstituted C 13 aryl, substituted or unsubstituted C 14 aryl, substituted or unsubstituted C 15 aryl, substituted or unsubstituted C 16 aryl, substituted or unsubstituted C 17 aryl, substituted or unsubstituted C 18 aryl, substituted or unsubstituted C 19 aryl, substituted or unsubstituted C 20 aryl), substituted or unsubstituted C6-C 20 heteroaryl is substituted with at least one substituent selected from the group consisting of C1-C 10 straight chain alkyl (e.g., C1straight chain alkyl, C2straight chain alkyl, C3straight chain alkyl, C4straight chain alkyl, C5straight chain alkyl, C6straight chain alkyl, C7straight chain alkyl, C8straight chain alkyl, C9straight chain alkyl, C 10 straight chain alkyl), C3-C 10 branched alkyl (e.g., C3branched alkyl, C4branched alkyl, C5branched alkyl, C6branched alkyl), methoxy, =0, phenyl, p-chlorobenzoyl;

[0058] (iv) R 4 is hydrogen;

[0059] R 2 and R 3 are each independently selected from the group consisting of substituted or unsubstituted C6-C 12 aryl (e.g., substituted or unsubstituted C6aryl, substituted or unsubstituted C7aryl, substituted or unsubstituted C8aryl, substituted or unsubstituted C9aryl, substituted or unsubstituted C 10 aryl, substituted or unsubstituted C 11 aryl, substituted or unsubstituted C 12 aryl), substituted or unsubstituted C4-C 12heteroaryl (e.g., substituted or unsubstituted C4 heteroaryl, substituted or unsubstituted C5 heteroaryl, substituted or unsubstituted C6 heteroaryl, substituted or unsubstituted C7 heteroaryl, substituted or unsubstituted C8 heteroaryl, substituted or unsubstituted C9 heteroaryl, substituted or unsubstituted C 10 heteroaryl, substituted or unsubstituted C 11 heteroaryl, substituted or unsubstituted C 12 heteroaryl, substituted or unsubstituted C1-C 10 straight chain alkyl (e.g., substituted or unsubstituted C1 straight chain alkyl, substituted or unsubstituted C2 straight chain alkyl, substituted or unsubstituted C3 straight chain alkyl, substituted or unsubstituted C4 straight chain alkyl, substituted or unsubstituted C5 straight chain alkyl, substituted or unsubstituted C6 straight chain alkyl, substituted or unsubstituted C7 straight chain alkyl, substituted or unsubstituted C8 straight chain alkyl, substituted or unsubstituted C9 straight chain alkyl, substituted or unsubstituted C 10 straight chain alkyl), substituted or unsubstituted C3-C 10 branched alkyl (e.g., substituted or unsubstituted C3 branched alkyl, substituted or unsubstituted C4 branched alkyl, substituted or unsubstituted C5 branched alkyl, substituted or unsubstituted C6 branched alkyl, substituted or unsubstituted C7 branched alkyl, substituted or unsubstituted C8 branched alkyl, substituted or unsubstituted C9 branched alkyl, substituted or unsubstituted C 10 branched alkyl), substituted or unsubstituted C3-C 10 cycloalkyl (e.g., substituted or unsubstituted C3 branched alkyl, substituted or unsubstituted C4 branched alkyl, substituted or unsubstituted C5 branched alkyl, substituted or unsubstituted C6 branched alkyl, substituted or unsubstituted C7 branched alkyl, substituted or unsubstituted C8 branched alkyl, substituted or unsubstituted C9 branched alkyl, substituted or unsubstituted C 10 branched alkyl), substituted or unsubstituted C3-C 10 heterocycloalkyl (e.g., substituted or unsubstituted C3 heterocycloalkyl, substituted or unsubstituted C4 heterocycloalkyl, substituted or unsubstituted C5 heterocycloalkyl, substituted or unsubstituted C6 heterocycloalkyl, substituted or unsubstituted C7 heterocycloalkyl, substituted or unsubstituted C8 heterocycloalkyl, substituted or unsubstituted C9 heterocycloalkyl, substituted or unsubstituted C 10 heterocycloalkyl);

[0060] or R 2 and R 3each independently selected from substituted or unsubstituted substituted or unsubstituted C1-C6 linear alkyl (e.g., substituted or unsubstituted C1 linear alkyl, substituted or unsubstituted C2 linear alkyl, substituted or unsubstituted C3 linear alkyl, substituted or unsubstituted C4 linear alkyl, substituted or unsubstituted C5 linear alkyl, substituted or unsubstituted C6 linear alkyl), substituted or unsubstituted C3-C6 branched alkyl (e.g., substituted or unsubstituted C3 branched alkyl, substituted or unsubstituted C4 branched alkyl, substituted or unsubstituted C5 branched alkyl, substituted or unsubstituted C6 branched alkyl), substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C3-C6 heterocycloalkyl.

[0061] In some embodiments, R 4 is hydrogen; R 2 , R 3 and the carbon atom to which each is attached collectively form a cyclohexyl group. 2 , R 3 each adjacent carbon atom collectively form a cyclohexyl group.

[0062] In some embodiments, R 4 is hydrogen; R 2 , R 3 and the carbon atom to which each is attached collectively form a cyclohexyl group, Ar is substituted or unsubstituted phenyl. 2 , R 3 each adjacent carbon atom collectively form a cyclohexyl group, Ar is substituted or unsubstituted phenyl.

[0063] In some embodiments, R 4 is hydrogen; R 2 , R 3 and the carbon atom to which each is attached collectively form a cyclohexyl group, Ar is substituted or unsubstituted phenyl; the substitution in the substituted phenyl is at least one hydrogen atom in the phenyl group is replaced with an amino group, a nitro group, a fluorine, a chlorine, a bromine, a methoxy group, -NMe2. 2 , R 3 each adjacent carbon atom collectively form a cyclohexyl group, Ar is substituted or unsubstituted phenyl.

[0064] In some embodiments, the compound a is selected from the group consisting of Compound 70, Compound 73-Compound 103, Compound 132-Compound 134, Compound a-1, Compound a-2, Compound a-3, Compound a-4, Compound a-5, Compound a-6, Compound a-7, Compound a-8, Compound a-9, Compound a-10, Compound a-11:

[0065]

[0066] In some embodiments, the compound c is selected from the group consisting of Compound 72, Compound 104-Compound 131, Compound 135-139, Compound c-1:

[0067]

[0068]

[0069] In some embodiments, the compound d is selected from the group consisting of Compound 1-Compound 56, Compound 58-Compound 69, Compound d-1, Compound d-2, Compound d-3, Compound d-1-S, Compound d-2-S, Compound d-3-S, Compound d-4, Compound d-4-S, Compound d-5, Compound d-5-S, Compound d-6, Compound d-6-S, Compound d-7, Compound d-7-S, Compound d-8, Compound d-8-S, Compound d-9, Compound d-9-S, Compound d-10, Compound d-10-S, Compound d-11, Compound d-11-S:

[0070]

[0071]

[0072] In some embodiments, the compound d is selected from the group consisting of Compound 1-R to Compound 56-R, Compound 58-R to Compound 69-R, Compound d-1-R, Compound d-2-R, Compound d-3-R, Compound d-4-R, Compound d-5-R, Compound d-6-R, Compound d-7-R, Compound d-8-R, Compound d-9-R, Compound d-10-R, Compound d-11-R:

[0073]

[0074]

[0075]

[0076] In some embodiments, the molar ratio of the compound a to the compound b is 1.0: 1.0-1.0:5.0. In some embodiments, the molar ratio of the compound a to the compound b is 1.0:1.0, 1.0:2.0, 1.0:3.0, 1.0:4.0, or 1.0:5.0. In some preferred embodiments, the molar ratio of the compound a to the compound b is 1.0:2.0.

[0077] In some embodiments, the molar ratio of the compound a to the compound c is 1.0: 1.0-1.0:5.0. In some embodiments, the molar ratio of the compound a to the compound c is 1.0:1.0, 1.0:2.0, 1.0:3.0, 1.0:4.0, or 1.0:5.0. In some preferred embodiments, the molar ratio of the compound a to the compound c is 1.0:4.0.

[0078] In some embodiments, the feed molar ratio of the compound a to the catalyst is 1.00:0.01-1.00:0.20. In some embodiments, the feed molar ratio of the compound a to the catalyst is 1.00:1.00:0.01, 1.00:0.05, 1.00:0.10, 1.00:0.15, or 1.00:0.20. In some preferred embodiments, the feed molar ratio of the compound a to the catalyst is 1.00:0.100.

[0079] In some embodiments, the feed molar ratio of the compound a to the ligand is 1.00:0.01-1.00:0.30. In some embodiments, the feed molar ratio of the compound a to the ligand is 1.00:0.01, 1.00:0.05, 1.00:0.10, 1.00:0.11, 1.00:0.12, 1.00:0.13, 1.00:0.14, 1.00:0.15, 1.00:0.20, 1.00:0.25, or 1.00:0.30. In some preferred embodiments, the feed molar ratio of the compound a to the ligand is 1.00:0.12.

[0080] In some embodiments, the feed molar ratio of the compound a to the base is 1.0:1.0-1.0:5.0. In some embodiments, the feed molar ratio of the compound a to the base is 1.0:1.0, 1.0:2.0, 1.0:3.0, 1.0:4.0, or 1.0:5.0. In some preferred embodiments, the feed molar ratio of the compound a to the base is 1.0:3.0.

[0081] In some embodiments, the feed molar ratio of the compound a to the silane is 1.0:1.0-1.0:5.0. In some embodiments, the feed molar ratio of the compound a to the silane is 1.0:1.0, 1.0:2.0, 1.0:3.0, 1.0:4.0, or 1.0:5.0. In some preferred embodiments, the feed molar ratio of the compound a to the silane is 1.0:4.0.

[0082] In some embodiments, 0.1 mol-1.0 mol of the compound a is fed per 1 L of the solvent. In some embodiments, 0.1 mol, 0.2 mol, 0.3 mol, 0.4 mol, 0.5 mol, 0.6 mol, 0.7 mol, 0.8 mol, 0.9 mol, or 1.0 mol of the compound a is fed per 1 L of the solvent. In some preferred embodiments, 0.5 mol of the compound a is preferably fed per 1 L of the solvent.

[0083] In some embodiments, the synthetic method comprises: under the condition of nitrogen or inert gas atmosphere, compound a, compound b and compound c are reacted in the presence of a catalyst, a ligand, a base, a silane and a solvent to obtain compound d.

[0084] In some embodiments, the synthetic method comprises: under the condition of nitrogen or inert gas atmosphere, compound a, compound b and compound c are mixed with a catalyst, a ligand, a base, a silane and a solvent to obtain a mixture, and then the mixture is taken out of the nitrogen or inert gas atmosphere to react to obtain compound d.

[0085] In some embodiments, the synthetic method comprises: mixing a catalyst and a ligand with a solvent, and then sequentially adding compound a, compound c, compound b, a base and a silane, mixing, and reacting to obtain compound d.

[0086] In some embodiments, the synthetic method comprises: under the condition of nitrogen or inert gas atmosphere, mixing a catalyst and a ligand with a solvent, and then sequentially adding compound a, compound c, compound b, a base and a silane, mixing, and reacting to obtain compound d.

[0087] In some embodiments, the synthetic method comprises: under the condition of nitrogen or inert gas atmosphere, mixing a catalyst and a ligand with a solvent, and then sequentially adding compound a, compound c, compound b, a base and a silane, mixing to obtain a mixture, and then taking the mixture out of the nitrogen or inert gas atmosphere to react to obtain compound d.

[0088] In some embodiments, the synthetic method further comprises post-treatment after the reaction is completed.

[0089] In some embodiments, the post-treatment comprises: adding water and ethyl acetate, separating into an aqueous phase and an organic phase, extracting the aqueous phase with ethyl acetate, combining the organic phases, washing the combined organic phase with saturated sodium chloride aqueous solution to remove residual water, and separating and purifying.

[0090] In a second aspect, the present application provides a compound.

[0091] A compound selected from the group consisting of: compound 4-compound 9, compound 13-compound 25, compound 27, compound 29, compound 31-compound 56, compound 58-compound 69, compound 4-R-compound 9-R, compound 13-R-compound 25-R, compound 27-R, compound 29-R, compound 31-R to compound 56-R, compound 58-R to compound 69-R, ligand L10-L21, ligand (R)-L10-ligand (R)-L21,

[0092]

[0093]

[0094]

[0095] In a third aspect, the present application provides a method for preparing a ligand compound.

[0096] In some embodiments, a method for preparing a ligand compound, the structure of the ligand compound is shown as compound S4, the method comprises: step 3: preparation of compound S4:

[0097]

[0098] Compound S3 is reacted with sodium methoxide in solvent 1, and after first post-treatment, a crude product C is obtained. The crude product C is reacted with compound S5 in the presence of a catalyst in solvent 2, and after second post-treatment, compound S4 is obtained; wherein the configuration of the chiral center marked by "*" in compound S5 is the same as the configuration of the chiral center marked by "*" in compound S4.

[0099] In some embodiments, the catalyst in step 3 comprises at least one of p-toluenesulfonic acid, hydrochloric acid.

[0100] In some embodiments, the solvent 1 comprises at least one of methanol, ethanol.

[0101] In some embodiments, the solvent 2 comprises at least one of toluene, ethylene glycol dimethyl ether, 1,4-dioxane.

[0102] In some embodiments, the reaction temperature of the reaction for preparing the crude product C in step 3 is 15-45°C. In some embodiments, the reaction temperature of the reaction for preparing the crude product C in step 3 is 15°C, 20°C, 25°C, 30°C, 35°C, 40°C or 45°C.

[0103] In some embodiments, the reaction temperature of the reaction of the crude product C with compound S5 in step 3 is 70-110°C. In some embodiments, the reaction temperature of the reaction of the crude product C with compound S5 in step 3 is 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C or 110°C.

[0104] In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1-1.0:1.0. In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1, 1.0:0.2, 1.0:0.3, 1.0:0.4, 1.0:0.5, 1.0:0.6, 1.0:0.7, 1.0:0.8, 1.0:0.9, or 1.0:1.0.

[0105] In some embodiments, 0.1 mol-0.5 mol of the compound S3 is charged per 1 L of the solvent 1. In some embodiments, 0.1 mol, 0.2 mol, 0.3 mol, 0.4 mol, or 0.5 mol of the compound S3 is charged per 1 L of the solvent 1.

[0106] In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1-1.0:1.0. In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1, 1.0:0.2, 1.0:0.3, 1.0:0.4, 1.0:0.5, 1.0:0.6, 1.0:0.7, 1.0:0.8, 1.0:0.9, or 1.0:1.0.

[0107] In some embodiments, 0.2 mol-1.0 mol of the crude product C is charged per 1 L of the solvent 2. In some embodiments, 0.2 mol, 0.3 mol, 0.4 mol, 0.5 mol, 0.6 mol, 0.7 mol, 0.8 mol, 0.9 mol, or 1.0 mol of the crude product C is charged per 1 L of the solvent 2.

[0108] In some embodiments, the molar ratio of the catalyst to the crude product C is 0.5:10.0-2.0:10.0. In some embodiments, the molar ratio of the catalyst to the crude product C is 0.5:10.0, 1.0:10.0, 1.5:10.0, or 2.0:10.0. In some embodiments, the molar ratio of the catalyst to the crude product C is 1.0:10.0.

[0109] In some embodiments, the first work-up comprises: removing the solvent 1, extracting with ethyl acetate and water, separating the layers, drying the ethyl acetate phase, filtering, and concentrating the filtrate.

[0110] In some embodiments, the second work-up comprises: quenching the reaction with water, extracting with ethyl acetate again, separating the layers, drying the ethyl acetate phase, filtering, concentrating the filtrate, and purifying.

[0111] In some embodiments, the R 5 , R 6 , R 7 is selected from any one of groups ①-Ⅳ:

[0112] i) said R 5 is selected from H, C1-C10 straight chain alkyl, C3-C10 branched chain alkyl;

[0113] said R 6 is selected from substituted or unsubstituted C1-C10 straight chain alkyl, substituted or unsubstituted C3-C10 branched chain alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl;

[0114] said R 7 is selected from substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl; or

[0115] ii) said R 5 is selected from H, C1-C10 straight chain alkyl; said R 6 is selected from t-butyl, phenyl, benzyl;

[0116] said R 7 is selected from phenyl,

[0117] or iii) said R 5 and R 7 form, with the adjacent carbon, a C6-C 12 aromatic ring; said R6is selected from substituted or unsubstituted C1-C10 straight chain alkyl, substituted or unsubstituted C3-C10 branched chain alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl;

[0118] or iv) said R 5 and R 7 form, with the adjacent carbon, a phenyl group; said R6is phenyl;

[0119] In some embodiments, the compound S4 is selected from the following structures:

[0120]

[0121] In some embodiments, the method of preparing the ligand compound further comprises a step of preparing compound S3:

[0122] Step 2: Preparation of compound S3:

[0123]

[0124] The compound S2 is reacted with an oxidizing agent in a solvent 3 to obtain a crude product A, the crude product A is reacted with trimethylsilyl cyanide and dimethylcarbamoyl chloride in a solvent 4, after a third work-up, to obtain the compound S3.

[0125] In some embodiments, the oxidizing agent comprises at least one of meta-chloroperoxybenzoic acid, hydrogen peroxide, peroxyacetic acid, urea hydrogen peroxide.

[0126] In some embodiments, the reaction temperature of the reaction to obtain the crude product A in step 2 is 15-35°C. In some embodiments, the reaction temperature of the reaction to obtain the crude product A in step 2 is 15°C, 20°C, 25°C, 30°C or 35°C.

[0127] In some embodiments, the reaction temperature of the reaction to obtain the compound S3 in step 2 is 15-35°C. In some embodiments, the reaction temperature of the reaction to obtain the compound S3 in step 2 is 15°C, 20°C, 25°C, 30°C or 35°C.

[0128] In some embodiments, the molar ratio of the compound S2 to meta-chloroperoxybenzoic acid is 1.0:1.0-1.0:2.0. In some embodiments, the molar ratio of the compound S2 to meta-chloroperoxybenzoic acid is 1.0:1.0, 1.0:1.5 or 1.0:2.0.

[0129] In some embodiments, 1L-5L of the solvent 3 is charged per 1 mol of the compound S2. In some embodiments, 1L, 2L, 3L, 4L or 5L of the solvent 3 is charged per 1 mol of the compound S2.

[0130] In some embodiments, the solvent 4 comprises at least one of dichloromethane, trichloromethane, ethyl acetate.

[0131] In some embodiments, the molar ratio of the crude product A to trimethylsilyl cyanide is 0.5:1.0-2.0:1.0. In some embodiments, the molar ratio of the crude product A to trimethylsilyl cyanide is 0.5:1.0, 1.0:1.0, 1.5:1.0 or 2.0:1.0.

[0132] In some embodiments, the molar ratio of the crude product A to dimethylcarbamoyl chloride is 0.5:1.0-2.0:1.0. In some embodiments, the molar ratio of the crude product A to dimethylcarbamoyl chloride is 0.5:1.0, 1.0:1.0, 1.5:1.0 or 2.0:1.0.

[0133] In some embodiments, 1L-5L of the solvent 4 is used per 1 mol of the crude product A. In some embodiments, 1L, 2L, 3L, 4L or 5L of the solvent 4 is used per 1 mol of the crude product A.

[0134] In some embodiments, the third work-up comprises: adding 10wt% potassium carbonate aqueous solution, mixing, adding dichloromethane, extracting, separating, washing the dichloromethane phase with saturated sodium chloride aqueous solution, drying the washed dichloromethane phase, filtering, concentrating the filtrate, and purifying.

[0135] In some embodiments, the method for preparing the ligand compound further comprises a step of preparing compound S2:

[0136] Step 1: Preparation of compound S2:

[0137]

[0138] Compound S1 and aryl boronic acid R 7 B(OH)2reacts in the presence of a base and a catalyst in a solvent 5 under the protection of nitrogen or inert gas atmosphere, and after a fourth work-up, compound S2 is obtained;

[0139] wherein R5and R 7 are selected from any one of the first- second groups described above, or the compound S4 is selected from structures L3, L4, L5, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, (R)-L3, (R)-L4, (R)-L5, (R)-L8, (R)-L9, (R)-L10, (R)-L11, (R)-L12, (R)-L13, (R)-L14, (R)-L15, (R)-L16, (R)-L17, (R)-L18, (R)-L19, (R)-L20, (R)-L21.

[0140] In some embodiments, the inert gas comprises at least one of helium, neon, argon, krypton, xenon.

[0141] In some embodiments, the base comprises at least one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, potassium phosphate.

[0142] In some embodiments, the catalyst comprises at least one of tetrakis(triphenylphosphine)palladium, palladium acetate, bis(triphenylphosphine)palladium chloride, palladium chloride.

[0143] In some embodiments, the solvent 5 is toluene, ethanol and water.

[0144] In some embodiments, the reaction temperature of the reaction of Step 1 is 80-100 °C. In some embodiments, the reaction temperature of the reaction of Step 1 is 80 °C, 85 °C, 90 °C, 95 °C, or 100 °C.

[0145] In some embodiments, the molar ratio of the compound S1 to the aryl boronic acid R 7 The molar ratio of the compound S1 to the aryl boronic acid R 7 The molar ratio of the compound S1 to the aryl boronic acid R

[0146] In some embodiments, the molar ratio of the compound S1 to the base is 1:5-1:10. In some embodiments, the molar ratio of the compound S1 to the base is 1:5, 1:6, 1:7, 1:8, 1:9, or 1:10.

[0147] In some embodiments, the molar ratio of the compound S1 to the catalyst is 1.00:0.01-1.00:0.10. In some embodiments, the molar ratio of the compound S1 to the catalyst is 1.00:0.01, 1.00:0.05, or 1.00:0.10.

[0148] In some embodiments, 5-10 L of the solvent 5 is charged for each 1 mol of the compound S1. In some embodiments, 5 L, 6 L, 7 L, 8 L, 9 L, or 10 L of the solvent 5 is charged for each 1 mol of the compound S1.

[0149] In some embodiments, the volume ratio of toluene, ethanol, and water in the solvent 5 is (30.0-40.0):(5.0-10.0):(30.0-40.0). In some embodiments, the volume ratio of toluene, ethanol, and water in the solvent 5 is (32.0-37.0):(6.0-8.0):(32.0-37.0). In some embodiments, the volume ratio of toluene, ethanol, and water in the solvent 5 is 35.0:7.5:35.0.

[0150] In some embodiments, the fourth work-up comprises adding an aqueous ammonium chloride solution, then extracting with ethyl acetate, combining the ethyl acetate phases and drying, and then concentrating and purifying.

[0151] In some embodiments, a method for preparing a ligand L6 comprises the following steps:

[0152]

[0153] The compound S3 is reacted with sodium methoxide in a solvent 6, a fifth post-treatment is performed, to obtain a crude product C, the crude product C is reacted with (1S,2R)-(-)-cis-1-amino-2-indanol in the presence of a catalyst in a solvent 7, a sixth post-treatment is performed, to obtain the ligand L6; wherein R 5 is H, R 7 is phenyl.

[0154] In some embodiments, the catalyst in the method of preparing the ligand L6 comprises at least one of p-toluenesulfonic acid, hydrochloric acid.

[0155] In some embodiments, the solvent 6 comprises at least one of methanol, ethanol.

[0156] In some embodiments, the solvent 7 comprises at least one of toluene, ethyleneglycol dimethyl ether, 1,4-dioxane.

[0157] In some embodiments, the reaction temperature of the reaction for preparing the crude product C in the method of preparing the ligand L6 is 15-45°C. In some embodiments, the reaction temperature of the reaction for preparing the crude product C in the method of preparing the ligand L6 is 15°C, 20°C, 25°C, 30°C, 35°C, 40°C or 45°C.

[0158] In some embodiments, the reaction temperature of the reaction of the crude product C with (1S,2R)-(-)-cis-1-amino-2-indanol in the method of preparing the ligand L6 is 70-110°C. In some embodiments, the reaction temperature of the reaction of the crude product C with (1S,2R)-(-)-cis-1-amino-2-indanol in the method of preparing the ligand L6 is 70°C, 75°C, 80°C, 85°C, 90°C, 95°C, 100°C, 105°C or 110°C.

[0159] In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1-1.0:1.0. In some embodiments, the molar ratio of the compound S3 to sodium methoxide is 1.0:0.1, 1.0:0.5 or 1.0:1.0.

[0160] In some embodiments, 0.1-0.5 mol of the compound S3 is charged per 1 L of the solvent 6. In some embodiments, 0.1 mol, 0.2 mol, 0.3 mol, 0.4 mol or 0.5 mol of the compound S3 is charged per 1 L of the solvent 6.

[0161] In some embodiments, the molar ratio of the crude product C to (1S,2R)-(-)-cis-1-amino-2-indanol in the feed is 1.0:1.0-1.0:1.5. In some embodiments, the molar ratio of the crude product C to (1S,2R)-(-)-cis-1-amino-2-indanol in the feed is 1.0:1.0, 1.0:1.1, 1.0:1.2, 1.0:1.3, 1.0:1.4, or 1.0:1.5.

[0162] In some embodiments, 0.2 mol-1.0 mol of the crude product C is fed per 1 L of the solvent 7. In some embodiments, 0.2 mol, 0.3 mol, 0.4 mol, 0.5 mol, 0.6 mol, 0.7 mol, 0.8 mol, 0.9 mol, or 1.0 mol of the crude product C is fed per 1 L of the solvent 7.

[0163] In some embodiments, the molar ratio of the catalyst to the crude product C in the feed is 0.5:10.0-2.0:10.0. In some embodiments, the molar ratio of the catalyst to the crude product C in the feed is 0.5:10.0, 1.0:10.0, 1.5:10.0, or 2.0:10.0. In some embodiments, the molar ratio of the catalyst to the crude product C in the feed is 1.0:10.0.

[0164] In some embodiments, the fifth post-treatment comprises: removing the solvent 6, extracting with ethyl acetate and water, separating the liquid, drying the ethyl acetate phase, filtering, and concentrating the filtrate.

[0165] In some embodiments, the sixth post-treatment comprises: quenching the reaction with water, extracting with ethyl acetate again, separating the liquid, drying the ethyl acetate phase, filtering, concentrating the filtrate, and purifying.

[0166] Advantages

[0167] Compared with the prior art, at least one of the following advantages is achieved in some embodiments of the present application:

[0168] (1) The synthesis method of the compound d provided by the present application has the advantages of simple operation, high safety, mild reaction, high yield, and high enantiomeric selectivity (high ee value), and has unexpected technical effects.

[0169] (2) The synthesis method of the ligand provided by the present application has the advantages of simple operation, high yield, and high purity of the product, and has unexpected technical effects.

[0170] Explanation of terms

[0171] In the present application, "room temperature" means ambient temperature, which can be 10°C to 40°C, which can be 20°C to 30°C; in some embodiments, 22°C to 28°C; in some embodiments, 24°C to 26°C; in some embodiments, 25°C.

[0172] In the above description of the present application, all numbers disclosed herein are approximate. Each numerical value, however, has a tolerance of ± 10% around the value itself, unless otherwise indicated.

[0173] The terms "optionally", "optional" or "optionally" mean that the subsequently described event or circumstance can but need not occur.

[0174] The term "and / or" should be understood to mean either one of the items or any combination of the items in the list.

[0175] In the present application, "C1-C 10 " includes any integer point value within the range of C1-C 10 , for example, C1, C2, C3, C4, C5, C6, C7, C8, C9, or C 10 . The definitions described for "C6-C 12 ", "C3-C 10 ", "C3-C 12 ", "C4-C 12 ", "C3-C 10 ", "C6-C 20 ", and the like follow the same logic, i.e., "C6-C 12 " includes any integer point value within the range of C6-C 12 , for example, C6, C7, C8, C9, C 10 , C 11 , C 12 .

[0176] "Alkyl" is a hydrocarbon containing primary carbon atoms, secondary carbon atoms, tertiary carbon atoms, or ring carbon atoms. For example, an alkyl group can have 1 to 10 carbon atoms (i.e., C1 alkyl, C2 alkyl, C3 alkyl, C4 alkyl, C5 alkyl, C6 alkyl, C7 alkyl, C8 alkyl, C9 alkyl, or C 10Alkyl groups, having 1 to 8 carbon atoms (i.e., C1-C8 alkyl) or 1 to 6 carbon atoms (i.e., C1-C6 alkyl). Examples of suitable alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), 1-propyl (i-Pr, i-propyl, -CH2CH2CH3), 2-propyl (i-Pr, i-propyl, -CH(CH3)2), 1-butyl (n-Bu, n-butyl, -CH2CH2CH2CH3), 2-methyl-1-propyl (i-Bu, i-butyl, -CH2CH(CH3)2), and 2-butyl (s-Bu, s-butyl, -CH2CH2CH2CH3). (CH3)CH2CH3), 2-methyl-2-propyl (t-Bu, t-butyl, -C(CH3)3), 1-pentyl (n-pentyl, -CH2CH2CH2CH2CH3), 2-pentyl (-CH(CH3)CH2CH2CH3), 3-pentyl (-CH(CH2CH3)2), 2-methyl-2-butyl (-C(CH3)2CH2CH3), 3-methyl-2-butyl (-CH(CH3)CH(CH3)2), 3-methyl-1-butyl ( -CH2CH2CH(CH3)2), 2-methyl-1-butyl(-CH2CH(CH3)CH2CH3), 1-hexyl(-CH2CH2CH2CH2CH2CH3), 2-hexyl(-CH(CH3)CH2CH2CH2CH3), 3-hexyl(-CH(CH2CH3)(CH2CH2CH3)), 2-methyl-2-pentyl(-C(CH3)2CH2CH2CH3), 3-methyl-2-pentyl(-CH(CH3)CH (CH3)CH2CH3), 4-methyl-2-pentyl (-CH(CH3)CH2CH(CH3)2), 3-methyl-3-pentyl (-C(CH3)(CH2CH3)2), 2-methyl-3-pentyl (-CH(CH2CH3)CH(CH3)2), 2,3-dimethyl-2-butyl (-C(CH3)2CH(CH3)2), 3,3-dimethyl-2-butyl (-CH(CH3)C(CH3)3 or octyl (-(CH2)7CH3).

[0177] "Alkenyl" refers to a group containing at least one unsaturated site, i.e., carbon-carbon sp. 2 Hydrocarbons with double bonds consisting of a positive, secondary, tertiary carbon atom, or a cyclic carbon atom. For example, alkenyl groups can have 2 to 10 carbon atoms (C2-C4). 10 alkenyl), 2 to 12 carbon atoms (C2-C) 12 Alkenyl groups, such as C2-alkenyl, C3-alkenyl, C4-alkenyl, C5-alkenyl, C6-alkenyl, C7-alkenyl, C8-alkenyl, C9-alkenyl, C... 10 alkenyl, C 11 alkenyl or C 12Alkenyl (or 2 to 6 carbon atoms, C2-C6 alkenyl). Examples of suitable alkenyl groups include, but are not limited to, ethylene or vinyl (-CH=CH2), allyl (-CH2CH=CH2), cyclopentenyl (-C5H7) and 5-hexenyl (-CH2CH2CH2CH2CH=CH2), propenyl, isopropenyl, butenyl, isobutenyl, pentenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl or pentadecenyl, etc.

[0178] "Alynyl" is a hydrocarbon containing at least one unsaturated carbon atom, namely a carbon-carbon sp triple bond, or a cyclic carbon atom. For example, an alkynyl group can have 2 to 10 carbon atoms (C2-C4). 10 alkynyl group), 2 to 12 carbon atoms (C2-C) 12 Alkynyl groups, such as C2-alkynyl, C3-alkynyl, C4-alkynyl, C5-alkynyl, C6-alkynyl, C7-alkynyl, C8-alkynyl, C9-alkynyl, C 10 alkynyl group, C 11 alkynyl or C 12 Alkyne group (or 2 to 6 carbon atoms, C2-C6 alkynyl). Examples of suitable alkynyl groups include, but are not limited to, ethynyl (-C=CH), propynyl (-CH2C=CH), or the like.

[0179] The term "carbocyclic group" or "carbocyclic" refers to a monovalent or polyvalent, non-aromatic, saturated or partially unsaturated monocyclic, bicyclic, or tricyclic system containing 3-12 carbon atoms. Bicyclic or tricyclic systems can include fused rings, bridged rings, and spirocyclic rings. Carbocyclic groups include spirocarbocyclic and fused carbocyclic groups; suitable carbocyclic groups include, but are not limited to, cycloalkyl, cycloalkenyl, and cycloynyl groups. In one embodiment, the carbocyclic group contains 3-10 carbon atoms, for example, C1... 3- C 10 A carbocyclic group; in another embodiment, the carbocyclic group comprises 3-8 carbon atoms, such as C 3- C8 carbocyclic group; in another embodiment, the carbocyclic group comprises 3-6 carbon atoms, such as C8. 3- C6 carbocyclic group. In another embodiment, the monocyclic carbocyclic group comprises 4-8 carbon atoms, such as C6. 4- C8 monocyclic carbocyclic group; in another embodiment, the monocyclic carbocyclic group comprises 4-6 carbon atoms, such as C 4-C6monocyclic carbocyclyl. Examples of carbocyclyl groups further include, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3- enyl, cyclohexyl, 1-cyclohexyl-1-enyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like. The carbocyclyl groups are optionally substituted with one or more substituents described herein. Examples of carbocyclyl groups further include, cyclopropyl, cyclobutyl, cyclopentyl, 1-cyclopentyl-1-enyl, 1-cyclopentyl-2-enyl, 1-cyclopentyl-3-enyl, cyclohexyl, 1-cyclohexyl-1-enyl, 1-cyclohexyl-2-enyl, 1-cyclohexyl-3-enyl, cyclohexadienyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl, cycloundecyl, cyclododecyl, and the like. When the structure clearly requires a linking group, the Markush variable recited for that group is to be understood as the linking group. For example, if the structure requires a linking group and the Markush group definition recited for that variable recites "carbocyclyl", it is to be understood that the "carbocyclyl" represents a linked carbocyclyl group.

[0180] "Aryl" means an aromatic hydrocarbon group derived by removing a hydrogen atom from a single carbon atom of a parent aromatic ring system. For example, aryl groups can have 6 to 20 carbon atoms (e.g., C6aryl, C7aryl, C8aryl, C9aryl, C10aryl, C11aryl, C12aryl, C13aryl, C14aryl, C15aryl, C16aryl, C17aryl, C18aryl, C19aryl, C20aryl). Typical aryl groups include, but are not limited to, groups derived from a benzene (e.g., phenyl), substituted benzenes, naphthalene, anthracene, tetrahydronaphthyl, phenanthryl, fluorenyl, or biphenyl, and the like. 10 aryl, C 11 aryl, C 12 aryl, C 13 aryl, C 14 aryl, C 15 aryl, C 16 aryl, C 17 aryl, C 18 aryl, C 19 aryl, or C 20 aryl), 6 to 14 carbon atoms, or 6 to 10 carbon atoms. Typical aryl groups include, but are not limited to, groups derived from a benzene (e.g., phenyl), substituted benzenes, naphthalene, anthracene, tetrahydronaphthyl, phenanthryl, fluorenyl, or biphenyl, and the like.

[0181] The term "heteroaryl" denotes monocyclic, bicyclic and tricyclic ring systems containing 3 to 20 ring atoms, 4 to 20 ring atoms, or 5 to 15 ring atoms, or 6 to 10 ring atoms, or 9 ring atoms, or 5 to 6 ring atoms, wherein at least one ring is aromatic and at least one aromatic ring contains one or more heteroatoms, wherein each ring system contains 5 to 7 atoms in a ring and has one or more points of attachment to the remainder of the molecule. The term "heteroaryl" can be used interchangeably with the terms "heteroaromatic," "heteroaromatic ring," or "heteroaromatic compound." In some embodiments, the heteroaryl is a 5 to 20 atom ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. In some embodiments, the heteroaryl is a 5 to 12 atom ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. In other embodiments, the heteroaryl is a 5 to 10 atom ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. In other embodiments, the heteroaryl is a 9 to 10 atom bicyclic ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. In other embodiments, the heteroaryl is a 9 atom ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. In other embodiments, the heteroaryl is a 5 to 6 atom monocyclic ring system containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of nitrogen, sulfur, and oxygen. And the heteroaryl can be substituted or unsubstituted, and the aryl group can be independently optionally substituted with one or more substituents described herein.

[0182] Examples of heteroaromatic rings include, but are not limited to, monocyclic heteroaryl groups such as 2-furanyl, 3-furanyl, N-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, N-pyrrolyl, 2-pyrrolyl, 3-pyrrolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, pyridazinyl (e.g., 3-pyridazinyl), 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, tetrazolyl (e.g., 5-tetrazolyl), triazolyl (e.g., 2-triazolyl and 5-triazolyl), 2-thiophenyl, 3-thiophenyl, pyranyl, pyrazolyl (e.g., 2-pyrazolyl), isothiazolyl, 1,2,3-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,4-oxadiazolyl, 1,2,3-triazolyl, 1,2,3-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyrazinyl, 1,3,5-triazinyl, dioxazinyl, thiadiazinyl, triazinyl, and the like; and bicyclic heteroaryl groups such as benzothiazolyl, benzimidazolyl, benzofuranyl, benzothienyl, indolyl (e.g., 2-indolyl), purinyl, quinolinyl (e.g., 2-quinolinyl, 3-quinolinyl, 4-quinolinyl), isoquinolinyl (e.g., 1-isoquinolinyl, 3-isoquinolinyl, or 4-isoquinolinyl), benzopyrazolyl, benzopyrrolyl, benzoxazolyl, 1,3-benzodioxolyl, benzisoxazolyl, isoquinolinyl (e.g., 1-isoquinolinyl, 3-isoquinolinyl, or 4-isoquinolinyl), imidazo[l,2-a]pyridinyl, pyrazolo[l,5-a]pyridinyl, pyrazolo[l,5-a]pyrimidinyl, imidazo[l,2-b]pyridazinyl, [l,2,4]triazolo[4,3-b]pyridazinyl, [l,2,4]triazolo[l,5-a]pyrimidinyl, [l,2,4]triazolo[l,5-a]pyridinyl, and the like.

[0183] The term "cycloalkyl" means a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 12 carbon atoms. In one embodiment, the cycloalkyl group contains 3 to 12 carbon atoms (e.g., 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 carbon atoms); in another embodiment, the cycloalkyl group contains 3 to 8 carbon atoms; in yet another embodiment, the cycloalkyl group contains 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. The cycloalkyl groups can be independently unsubstituted or substituted with one or more substituents described herein.

[0184] Examples of alkoxy groups include, but are not limited to, methoxy (MeO, -OCH3), ethoxy (EtO, -OCH2CH3), 1-propoxy (n-PrO, n-propoxy, -OCH2CH2CH3), 2-propoxy (i-PrO, i-propoxy, -OCH(CH3)2), 1-butoxy (n-BuO, n-butoxy, -OCH2CH2CH2CH3), 2-methyl-l-propoxy (i-BuO, i-butoxy, -OCH2CH(CH3)2), 2-butoxy (s-BuO, s-butoxy, -OCH(CH3)CH2CH3), 2-methyl-2-propoxy (t-BuO, t-butoxy, -OC(CH3)3), and so on.

[0185] The term "substituted" refers to alkyl, aryl, arylalkyl, heterocyclic, heteroaryl, carbocyclic, etc., such as "substituted C1-C". 10 Alkyl, substituted C6-C 20 "Aryl", "Substituted arylalkyl", "Substituted C1-C" 20 "Heterocyclic" and "substituted carbocyclic" refer to C1-C rings in which one or more hydrogen atoms are independently replaced by non-hydrogen substituents, respectively. 10 Alkyl, C6-C 20 Aryl, arylalkyl, C1-C 20 Heterocyclic, carbocyclic. Unless otherwise stated, a substituted group may have one substituent at each substituted position of the group. When more than one position in the given structural formula can be substituted by one or more substituents selected from a particular group, the substituents may be substituted at each position in the same or different manner.

[0186] "Trace" refers to a yield that is extremely small, almost negligible, typically less than 1%.

[0187] The term "unsubstituted" means that the specified group does not have substituents.

[0188] The term "consisting of" or "consisting" means "including and limited to." The term "j-k atoms" or "j-k membered" means that the cyclic group consists of j-k ring atoms, including carbon atoms and / or O, N, S, P, and the like heteroatoms; j and k are each independently any non-zero natural number, and k > j; "j-k" includes j, k, and any natural number in between. For example, "3-8 atoms" or "3-8 membered," "3-6 atoms" or "3-6 membered," "5-10 atoms" or "5-10 membered," "5-6 atoms" or "5-6 membered" means that the cyclic group consists of 3-8 (i.e., 3, 4, 5, 6, 7, or 8), 3-6 (i.e., 3, 4, 5, or 6), 5-10 (i.e., 5, 6, 7, 8, 9, or 10), or 5-6 (i.e., 5 or 6) ring atoms, including carbon atoms and / or O, N, S, P, and the like heteroatoms. For another example, piperidinyl is a 6 atom containing heterocyclyl or 6 membered heterocyclyl, while pyridinyl is a 6 atom containing heteroaryl or 6 membered heteroaryl.

[0189] The term "j-k," "j-k membered," or "C j -C k The j and k in "j-k" are each independently any non-zero natural number, and k > j; for example, "1-4" means 1, 2, 3, or 4, and "4-6 membered" means 4 membered, 5 membered, or 6 membered; "C3-C6" means C3, C4, C5, or C6. And so on.

[0190] "Heterocycle" or "heterocyclyl" includes, by way of example and without limitation, those described in Paquette, Leo A.; Principles of Modern Heterocyclic Chemistry (W.A. Benjamin, New York, 1968), particularly Chapters 1, 3, 4, 6, 7, and 9; The Chemistry of Heterocyclic Compounds, A Series of Monographs (John Wiley & Sons, New York, 1950 to present), in particular Volumes 13, 16, 19, and 28; and J. Am. Chem. Soc. (1960) 82:5566. In one specific embodiment of the application, "heterocycle" includes "carbocycle" as defined herein, wherein one or more (e.g., 1, 2, 3, or 4) carbon atoms have been replaced with a heteroatom such as, for example, O, N, or S. The term "heterocycle" or "heterocyclyl" includes saturated, partially unsaturated, and aromatic (i.e., heteroaromatic) rings. Substituted heterocyclyl includes, for example, heterocyclyl substituted with any of the substituents disclosed herein including carbonyl.

[0191] The terms "heterocyclic group" and "heterocycle" are used interchangeably herein, referring to a non-aromatic, saturated or partially unsaturated monocyclic, bicyclic, or tricyclic system comprising 3-12 ring atoms, wherein the bicyclic or tricyclic system may include fused rings, bridged rings, and spirocyclic rings. One or more atoms on the ring are independently replaced by heteroatoms, which have the meaning as described in this invention. In one embodiment, the heterocyclic group is a monocyclic heterocyclic group consisting of 3-8 ring atoms (1-7 carbon atoms and 1-4 heteroatoms selected from N, O, P, or S, wherein S or P is optionally substituted with one or more oxygen atoms to obtain a group like SO, SO2, PO, PO2); in another embodiment, the heterocyclic group is a monocyclic heterocyclic group consisting of 3-6 ring atoms (1-5 carbon atoms and 1-4 heteroatoms selected from N, O, P, or S, wherein S or P is optionally substituted with one or more oxygen atoms to obtain a group like SO, SO2, PO, PO2); in yet another embodiment, the heterocyclic group is a bicyclic heterocyclic group consisting of 7-12 ring atoms (1-11 carbon atoms and 1-4 heteroatoms selected from N, O, P, or S, wherein S or P is optionally substituted with one or more oxygen atoms to obtain a group like SO, SO2, PO, PO2). The heterocyclic group is optionally substituted with one or more substituents described in this invention.

[0192] The ring atom of the heterocyclic group can be carbon-based or heteroatom-based. Optionally, the -CH2- group of the ring is replaced by -C(=O)-, the sulfur atom of the ring is optionally oxidized to S-oxide, and the nitrogen atom of the ring is optionally oxidized to N-oxygen compound. Examples of heterocyclic groups include, but are not limited to, ethylene oxide, azirrobutyl, oxacyclobutyl, thioheterobutyl, pyrrolyl, 2-pyrrololinyl, 3-pyrrololinyl, pyrazolinyl, pyrazolyl, imidazolinyl, imidazolinyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydrothiophenyl, dihydrothiophenyl, 1,3-dioxocyclopentyl, dithiocyclopentyl, tetrahydropyranyl, dihydropyranyl, 2H-pyranyl, 4H-pyranyl, tetrahydrothiophenyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazine, dioxane, dithiaalkyl, thiaalkyl, homopiperazine, homopiperidinyl, oxacycloheptyl, thioheptanyl, oxacycloheptyl, oxacyclobutyl... 2-diazine Base, sulfur nitrogen Examples of heterocyclic groups include, but are not limited to, 2-oxa-5-azabicyclo[2,2,1]hept-5-yl, etc. Examples of heterocyclic groups where the -CH2- group is substituted with -C(=O)- include, but are not limited to, 2-oxopyrrolyl, oxo-1,3-thiazolyl, 2-piperidinone, 3,5-dioxopyridine, pyrimidinedionyl, etc. Examples of heterocyclic groups where the sulfur atom is oxidized include, but are not limited to, sulfolane, thiomorpholinyl 1,1-dioxide, etc. The heterocyclic groups may optionally be substituted with one or more substituents described in this invention.

[0193] The term "heterocycloalkyl" refers to a monovalent or polyvalent saturated monocyclic, bicyclic or tricyclic ring system containing 3 to 20 ring atoms, at least one of which is a nitrogen, sulfur or oxygen atom.

[0194] Examples of heterocycles include, by way of example and not limitation, pyridyl, dihydropyridyl, tetrahydropyridyl (piperidyl), thiazolyl, tetrahydrothienyl, sulfoxidized tetrahydrothienyl, pyrimidinyl, furanyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, tetrazolyl, benzofuranyl, thianaphthalenyl, indolyl, indolenyl, quinolyl, isoquinolyl, benzimidazolyl, piperidyl, 4-piperidonyl, pyrrolidinyl, 2-pyrrolidonyl, pyrrolinyl, tetrahydrofuranyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, octahydroisoquinolinyl, azocinyl (azocane), triazinyl, 6H-l,2,5-thiadiazinyl, 2H,6H-l,5,2-dithiazinyl, thienyl, thianthrenyl, pyranyl, isochromenyl, chromenyl, coumarinyl, 2H-pyrrolyl, isothiazolyl, isoxazolyl, pyrazinyl, pyridazinyl, indolizinyl, isoindolyl, 3H-indolyl, lH-indazolyl, purinyl, 4H-quinolizinyl, phthalazinyl, naphthyridinyl, quinoxalinyl, quinazolinyl, cinnolinyl, pteridinyl, 4aH-carbazolyl, carbazolyl, β-carbolinyl, phenanthridinyl, acridinyl, pyrimidinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, furazanyl, phenoxazinyl, isochromanyl, chromanyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperazinyl, indolinyl, isoindolinyl, quinuclidinyl, morpholinyl, oxazolidinyl, benzotriazolyl, benzisoxazolyl, oxindolyl, benzoxazolinyl, indatrinyl, and bis-tetrahydrofuranyl.

[0195] The term "V / V" means volume ratio.

[0196] The term "wt%" means mass percent.

[0197] "Me" means methyl; "Et" means ethyl; "Ph" means phenyl; "Bu" means butyl; "i-Pr" or "i-Pr" means isopropyl; "nPr" or "n-Pr" means n-propyl; "n-Bu" means n-butyl; "i-Bu" means isobutyl; "t-Bu" means tert-butyl; "n-Hex" or "n-Hex" means n-hexyl; "n-C4H9" means n-butyl; "n-C5H t Bu" means tert-butyl; "i-Pr" or "i-Pr" means isopropyl; "nPr" or "n-Pr" means n-propyl; "n-Bu" means n-butyl; "i-Bu" means isobutyl; "t-Bu" means tert-butyl; "n-Hex" or "n-Hex" means n-hexyl; "n-C4H i 9" means n-butyl; "n-C5H n 11" means n-pentyl; "n-C6H 11 12" means n-hexyl; "n-C7H 13"n-hexyl" means n-hexyl; " -OTBS" or "TBSO-" means dimethyl-tert-butylsilyl ether; " -OAc" means acetyloxy (i.e., CH3COO-); "n-butyl" means n-butyl; "n-amyl" means n-amyl; "OBz" means benzoyl; "Cy" means cyclohexyl; "Boc" means tert-butoxycarbonyl; "Ts" means p-toluenesulfonyl; "Bn" means benzyl; "NHPiv" means pivalamido.

[0198] The group "THPO-" means The group "PhthN-" means

[0199] The term "equiv" means equivalent, with 1.0 equiv of a substance in a reaction being the equivalent ratio of moles of each substance.

[0200] The term "M" means mol / L.

[0201] NiI2 means nickel iodide (CAS No. 13462-90-3); NiBr2 means nickel bromide (CAS No. 13462-88-9); NiCl2 means nickel chloride (CAS No. 7718-54-9); NiBr2-DME means nickel bromide ethylene glycol dimethyl ether (CAS No. 28923-39-9); NiCl2-6H2O means nickel chloride hexahydrate (CAS No. 7791-20-0); Ni(COD)2 means bis(l,5-cyclooctadiene)nickel (CAS No. 1295-35-8); Ni(acac)2 means nickel acetylacetonate (CAS No. 3264-82-2); Ni(OTf)2 means nickel triflate (CAS No. 60871-84-3); Ni(OAc)2 means nickel acetate (CAS No. 373-02-4); Ni(OAc)2-4H2O means nickel acetate tetrahydrate (CAS No. 6018-89-9). TsOH means p-toluenesulfonic acid (CAS No. 104-15-4).

[0202] The wavy bond in compound a indicates that both cis and trans configurations are possible.

[0203] As used herein, the term "treatment" means any clinical intervention designed to alter the natural course of the disease in the individual being treated. Desired effects of treatment include, but are not limited to, preventing occurrence or reoccurrence of disease, alleviating symptoms, lessening any direct or indirect pathological consequences of the disease, preventing metastasis, decreasing rate of disease progression, ameliorating or palliating the disease state, and remission or improvement in prognosis.

[0204] In the description of this specification, the references to terms such as "one embodiment," "some embodiments," "example," "specific example," or "some examples," etc., indicate that a specific feature, structure, material, or characteristic described in connection with that embodiment or example is included in at least one embodiment or example of the present invention. In this specification, the illustrative expressions of the above terms do not necessarily refer to the same embodiment or example. Furthermore, the specific features, structures, materials, or characteristics described may be combined in any suitable manner in one or more embodiments or examples. Moreover, without contradiction, those skilled in the art can combine and integrate the different embodiments or examples described in this specification, as well as the features of different embodiments or examples.

[0205] In this application, the "composition" can be conveniently presented in unit dose form and can be prepared by any method well known in the pharmaceutical industry. All methods involve the step of combining the active ingredient with a carrier constituting one or more adjunct components. Typically, the composition is prepared by uniformly and sufficiently combining the active compound with a liquid carrier, a finely pulverized solid carrier, or both.

[0206] Additionally, it should be noted that, unless otherwise explicitly stated, the descriptive phrases “each and each is independently”, “each and each is independently”, and “each and each is independently” used throughout this document are interchangeable and should be interpreted broadly. They can mean either that the specific options expressed by the same symbols in different groups do not affect each other, or that the specific options expressed by the same symbols in the same group do not affect each other. Attached Figure Description

[0207] Figure 1 The spatial configuration of compound 49 is shown in the ball-and-stick model diagram. Detailed Implementation

[0208] To enable those skilled in the art to better understand the technical solutions of the present invention, some non-limiting embodiments are further disclosed below to provide a more detailed description of the present invention.

[0209] All reagents used in this invention can be purchased from the market or prepared by the methods described in this invention or by conventional methods in the art.

[0210] Example 1: Synthesis of ligands

[0211] Method 1: Synthesize ligands L3-L5, L8-L21, (R)-L3~(R)-L5, (R)-L8~(R)-L15, etc., according to the following steps:

[0212]

[0213] Step 1: Add sodium carbonate (75.0 mmol, 7.5 equivalents), tetrakis(triphenylphosphine)palladium (0.3 mmol), and arylboronic acid (R... 7 B(OH)₂, 13.0 mmol, 1.3 equivalents, R in arylboronic acid 7 The structure of the compound corresponding to the final product compound S4 is R 7 (The groups were determined) and mixed. Compound S1 (10.0 mmol, 1.0 equiv, R of compound S1) was added under nitrogen atmosphere. 5 The structure is based on the R of the compound corresponding to the final product compound S4. 5 The radical groups were identified. Toluene (35.0 mL), ethanol (7.5 mL), and water (35.0 mL) were added and refluxed in an oil bath at 90 °C. The reaction was monitored by thin-layer chromatography. After the reaction was complete, ammonium chloride aqueous solution (15.0 mL) was added, and the mixture was extracted three times with ethyl acetate. The extract was dried over anhydrous sodium sulfate and evaporated under vacuum to obtain the crude product. The crude product was purified by silica gel column chromatography with petroleum ether / ethyl acetate to obtain the corresponding compound S2 (yield 24%-78%, purity >95%).

[0214] Step 2-1: Dissolve compound S2 (1.0 equivalent) in dichloromethane (30.0 mL), add m-chloroperoxybenzoic acid (1.2 equivalent) at 0 °C, and stir at room temperature. Monitor the reaction by thin-layer chromatography. After the reaction is complete, quench the mixture with 10% sodium thiosulfate aqueous solution and 10% sodium hydroxide aqueous solution; filter, and concentrate the filtrate under vacuum to obtain crude product A, which can be used in the next step without further purification.

[0215] Step 2-2: Dissolve crude product A obtained in Step 2-1 in 30.0 mL of dichloromethane to obtain a crude product A solution. Add trimethylcyanosilane (1.1 equivalents) to the crude product A solution at room temperature. After stirring for 10 min, add 1.1 equivalents of dimethylcarbamoyl chloride and stir at room temperature. Monitor the reaction by thin-layer chromatography. After the reaction is complete, stir with 20.0 mL of 10% potassium carbonate aqueous solution for 30 min. Extract the mixture with dichloromethane. Wash the bound organic phase with saturated sodium chloride aqueous solution, dry on anhydrous sodium sulfate, and filter. Concentrate the filtrate under vacuum to obtain crude product B. Purify crude product B by silica gel column chromatography to obtain compound S3 (overall yield of steps 2-1 to 2-2 is 70%-95%, product purity is >95%).

[0216] Step 3: Dissolve 1.0 equivalent of compound S3 in anhydrous methanol to obtain a methanol solution containing 0.3 mol / L of compound S3. Then add 1.0 equivalent of sodium methoxide and stir at room temperature for 12 h. Remove the solvent from the reaction mixture under vacuum to obtain a residue. Extract the residue with ethyl acetate and water, separate the layers, dry the organic layer on anhydrous sodium sulfate, filter, and concentrate under vacuum to obtain crude product C. Dissolve all the obtained crude product C in toluene to obtain a toluene solution containing 0.5 mol / L of crude product. Add 1.2 equivalent of the corresponding compound S5 (the R6 group of compound S5 is the same as the R6 group of the compound corresponding to the final product S4, and the configuration of the chiral center (carbon indicated by "*") of compound S5 is the same as that of compound S4) and TsOH (10 mol%, i.e., the molar amount of TsOH added is one-tenth of the molar amount of crude product C). Heat the reaction solution in an oil bath at 80 °C until the reaction is complete (TLC monitoring of the reaction). Quench the reaction with water, then extract the mixture with ethyl acetate and combine the organic layers. The combined organic layers were dried with anhydrous sodium sulfate, filtered, and concentrated under vacuum to obtain crude product D. Crude product D was purified by silica gel column chromatography to obtain compound S4 (ligands L3-L5, L8-L21, (R)-L3 to (R)-L5, (R)-L8 to (R)-L15, etc.). The yields and purities of each ligand in step 3 are shown in Table 1.1.

[0217] Table 1.1: Yields and purity of each ligand product in step 3

[0218] ligand Step 3 yield Step 3 product purity ligand L3 61％ ＞95％ ligand L4 56％ ＞95％ ligand L5 62％ ＞95％ ligand L8 57％ ＞95％ ligand L9 60％ ＞95％ ligand L10 55％ ＞95％ ligand L11 56％ ＞95％ ligand L12 54％ ＞95％ ligand L13 61％ ＞95％ ligand L14 48％ ＞95％ ligand L15 52％ ＞95％ ligand L16 63％ ＞95％ ligand L17 57％ ＞95％ ligand L18 54％ ＞95％ ligand L19 61％ ＞95％ ligand L20 55％ ＞95％ ligand L21 59％ ＞95％ ligand (R)-L3 60％ ＞95％ ligand (R)-L4 58％ ＞95％ ligand (R)-L5 56％ ＞95％ ligand (R)-L8 53％ ＞95％ ligand (R)-L9 57％ ＞95％ ligand (R)-L10 55％ ＞95％ ligand (R)-L11 56％ ＞95％ ligand (R)-L12 58％ ＞95％ ligand (R)-L13 59％ ＞95％ ligand (R)-L14 44％ ＞95％ ligand (R)-L15 51％ ＞95％

[0219] Method 2: Prepare ligand L7 and ligand (R)-L7 according to the following steps:

[0220]

[0221] (In compounds S2, S3, and S4, R) 5 and R 7 It forms a benzene ring with the adjacent carbon, and R6 is Ph.

[0222] Starting directly from step 2 of Method 1 above, replace compound S2 with the same molar amount of quinoline and proceed with subsequent steps 2-4 to obtain compound S4 (ligand L7 or ligand (R)-L7). The yields and purities of the products in each step of Method 2 are shown in Table 1.2.

[0223] Table 1.2: Product yield and purity of each step in Method 2

[0224]

[0225] Method 3: Prepare ligand L6 according to the following steps:

[0226] Steps 1-3 are the same as in Steps 1-3 of the above method (wherein in compounds S2, S3, R 5 is H, R 7 is Ph).

[0227]

[0228] Step 4: Replace compound S5 with the same molar amount of (1S,2R)-(-)-cis-1- amino-2-indanol, and follow the rest of the procedure of Step 4 of the above method to give ligand L6. The yield of Step 4 ligand L6 is 65% with a purity of >95%.

[0229] The structures and characterization of each ligand are as follows:

[0230]

[0231]

[0232]

[0233]

[0234] Example 2: Reaction condition screening investigation (1) Screening of ligands

[0235]

[0236] Procedure: Under a nitrogen atmosphere, mix Ni(OAc)2-4H2O (0.01 mmol), ligand (0.012 mmol, see Table 2 for ligand selection), and 2-methyltetrahydrofuran (0.2 mL), stir at 25 °C for 10 min, then add compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e., compound 71), (0.20 mmol), and NaHCO3(0.30 mmol) sequentially. Stir the resulting mixture for another 5 min, then add trimethoxysilane (0.40 mmol) dropwise. Remove the reaction from the nitrogen atmosphere, and stir at 25 °C for 24 h. After the reaction is complete, determine the yield by GC using dodecane as an internal standard. Determine the enantiomeric excess by HPLC (results in Table 2).

[0237] Obtain compound 1 and perform NMR and13C NMR analysis, with the following results:

[0238] 1 H NMR(400 MHz, Chloroform-d) δ 7.33 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 3.73 (q, J = 7.0 Hz, 1H), 2.38-2.31 (m, 2H), 1.53-1.43 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.31 (s, 9H), 1.28-1.24 (m, 2H), 1.22-1.13 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H).

[0239] 13 C NMR (101 MHz, Chloroform-d) δ 211.5, 149.9, 137.6, 127.5, 125.7, 52.4, 41.0, 34.4, 31.8, 31.3, 29.3, 29.23, 29.18, 23.9, 22.6, 17.4, 14.1.

[0240] Table 2:

[0241] experiment ligand yield ee 1 L1 trace - 2 L2 trace - 3 L3 65％ 23％ 4 L4 trace - 5 L5 trace - 6 L6 trace - 7 L7 trace - 8 L8 66％ 52％ 9 L9 75％ 77％

[0242] Each ligand structure is as follows:

[0243]

[0244] Procedure: Under nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L9 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71), (0.20 mmol) and the corresponding base (0.30 mmol, see Table 3 for base selection) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of nitrogen atmosphere and stirred at 25 °C for 24 h. After the reaction was completed, the yield was determined by GC with dodecane as internal standard. The enantiomeric excess was determined by high performance liquid chromatography (results are shown in Table 3).

[0245] Table 3:

[0246] experiment base yield ee 1 Na2CO3 65％ 77％ 2 NaHCO3 75％ 77％ 3 [K2CO3] 64％ 77％ 4 Cs2CO3 45％ 77％

[0247] (3) Solvent screening

[0248]

[0249] Procedure: Under nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L9 (0.012 mmol) and the corresponding solvent (0.2 mL, see Table 4 for the choice of solvent) were mixed and stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at 25 °C for 24 h. After the reaction was completed, the yield was determined by GC with dodecane as the internal standard. The enantiomeric excess was determined by HPLC (results in Table 4).

[0250] Table 4: (4) Screening of nickel catalysts

[0251]

[0252] Procedure: Under nitrogen atmosphere, nickel catalyst (0.01 mmol, see Table 5 for the choice of nickel catalyst), ligand L9 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at 25 °C for 24 h. After the reaction was completed, the yield was determined by GC with dodecane as the internal standard. The enantiomeric excess was determined by HPLC (results in Table 5).

[0253] Table 5:

[0254] experiment nickel catalyst yield ee 1 [NiI2] 32％ 77％ 2 [NiBr2] 60％ 77％ 3 [NiCl2] 62％ 77％ 4 [NiBr2.DME] 48％ 77％ 5 [NiCl2-6H2O] 62％ 77％ 6 [Ni(COD)2] 60％ 77％ 7 [Ni(acac)2] 14％ 77％ 8 Ni(OTf)2 15％ 77％ 9 [Ni(OAc)2·4H2O] 75％ 77％

[0255] (5) Screening of ligands

[0256]

[0257] Procedure: Ni(OAc)2-4H2O (0.01 mmol), ligand (0.012 mmol, see Table 6 for ligand selection) and 2-methyltetrahydrofuran (0.2 mL) were mixed under nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71), (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at 25 °C for 24 h. After the reaction was completed, the yield was determined by GC with dodecane as the internal standard. The enantiomeric excess was determined by HPLC (results in Table 6).

[0258] Table 6:

[0259] experiment ligand yield ee 1 L8 66％ 52％ 2 L9 75％ 77％ 3 L10 78％ 77％ 5 L11 77％ 78％ 6 L12 82％ 83％ 7 L13 87％ 83％ 8 L14 86％ 87％ 6 L15 91％ 87％

[0260] The structure of each ligand is as follows:

[0261]

[0262] (6) Investigation of temperature

[0263]

[0264] Procedure: Ni(OAc)2-4H2O (0.01 mmol), ligand (0.012 mmol, see Table 6 for ligand selection) and 2-methyltetrahydrofuran (0.2 mL) were mixed under nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71), (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at 25 °C for 24 h. After the reaction was completed, the yield was determined by GC with dodecane as the internal standard. The enantiomeric excess was determined by HPLC (results in Table 6).

[0265] Table 7:

[0266] experiment ligand reaction temperature yield ee 1 L14 -10℃ 89% (83% isolated yield) 93％ 2 L15 -10℃ 92％ 91％

[0267] The structure of ligand L14, ligand L15 is as follows:

[0268] Example 3: Preparation of compound 1

[0269]

[0270] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively to obtain a mixture. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise to obtain a reaction solution. The reaction solution was taken out from the nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added for dilution. After the reaction solution was layered, the aqueous phase was extracted with ethyl acetate twice (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography separation and purification were performed to obtain compound 1 in the form of colorless oil with a yield of 83%, an enantiomeric excess of 93% determined by high performance liquid chromatography, and the following results were obtained by detecting the hydrogen spectrum and carbon spectrum of the obtained compound 1: 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 3.73 (q, J = 7.0 Hz, 1H), 2.38-2.31 (m, 2H), 1.53-1.43 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.31 (s, 9H), 1.28-1.24 (m, 2H), 1.22-1.13 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.5, 149.9, 137.6, 127.5, 125.7, 52.4, 41.0, 34.4, 31.8, 31.3, 29.3, 29.23, 29.18, 23.9, 22.6, 17.4, 14.1.

[0271] Example 4: Preparation of compound 2

[0272]

[0273] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 73 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL water and 5 mL ethyl acetate were added for dilution. After the reaction was layered, the aqueous phase was extracted with ethyl acetate twice (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used for separation and purification, to obtain compound 2 in the form of colorless oil, with a yield of 82%, an enantiomeric excess of 94% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 2:

[0274] 1 H NMR (400 MHz, Chloroform-d) δ 7.11 (q, J = 8.2 Hz, 4H), 3.71 (q, J = 6.9 Hz, 1H), 2.33 (d, J = 3.3 Hz, 5H), 1.51 - 1.43 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.24 (s, 2H), 1.21 - 1.09 (m, 8H), 0.87 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.5, 137.9, 136.8, 129.7, 127.9, 52.7, 41.1, 31.9, 29.4, 29.24, 29.20, 24.0, 22.8, 17.6, 14.2.

[0275] Example 5: Preparation of compound 3

[0276]

[0277] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 74 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 3 as a colourless oily liquid, with a yield of 80% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 3 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0278] 1 H NMR (400 MHz, Chloroform-d) δ 7.57 (t, J = 8.4 Hz, 4H), 7.44 (t, J = 7.6 Hz, 2H), 7.34 (t, J = 7.3 Hz, 1H), 7.29 (d, J = 8.2 Hz, 2H), 3.80 (q, J = 6.9 Hz, 1H), 2.42-2.37 (m, 2H), 1.56-1.47 (m, 2H), 1.43 (d, J = 7.0 Hz, 3H), 1.27-1.24 (m, 2H), 1.22-1.15 (m, 8H), 0.85 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 140.8, 140.1, 139.9, 128.9, 128.4, 127.7, 127.4, 127.1, 52.7, 41.3, 31.9, 29.4, 29.3, 29.2, 24.0, 22.8, 17.6, 14.2.

[0279] Example 6: Preparation of compound 4

[0280]

[0281] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 75 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 4 as a colourless oily liquid, with a yield of 95% and an enantiomeric excess of 94% determined by high performance liquid chromatography. The compound 4 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0282] 1 H NMR (400 MHz, Chloroform-d) δ 7.47 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 3.74 (q, J = 6.9 Hz, 1H), 2.35 (t, J = 7.3 Hz, 2H), 1.52-1.42 (m, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.26-1.23 (m, 2H), 1.22-1.13 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H), 0.26 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 141.4, 139.2, 134.0, 127.4, 53.0, 41.3, 31.9, 29.4, 29.23, 29.19, 24.0, 22.8, 17.6, 14.2, -1.0.

[0283] Example 7: Preparation of compound 5

[0284]

[0285] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 76 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at 0 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction liquid was separated into two layers, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 5 as a colorless oily liquid, with a yield of 75%, an enantiomeric excess of 90% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 5:

[0286] 1 H NMR (400 MHz, Chloroform-d) δ 7.49 (d, J = 8.6 Hz, 2H), 7.35 (s, 1H), 7.15 (d, J = 8.5 Hz, 2H), 3.71 (q, J = 6.9 Hz, 1H), 2.32 (t, J = 7.0 Hz, 2H), 1.50-1.40 (m, 2H), 1.34 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.24 (d, J = 7.8 Hz, 2H), 1.21-1.09 (m, 8H), 0.85 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 176.8, 137.1, 136.7, 128.5, 120.5, 52.4, 41.1, 39.7, 31.9, 29.4, 29.20, 29.19, 27.7, 24.0, 22.7, 17.6, 14.2.

[0287] Example 8: Preparation of compound 6

[0288]

[0289] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 77 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 6 as a colourless oily liquid, with a yield of 71% and an enantiomeric excess of 95% as determined by high performance liquid chromatography. The compound 6 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0290] 1 H NMR (400 MHz, Chloroform-d) δ 7.21 (d, J = 8.6 Hz, 2H), 7.04 (d, J = 8.5 Hz, 2H), 3.75 (q, J = 7.0 Hz, 1H), 2.37-2.31 (m, 2H), 2.29 (d, J = 1.3 Hz, 3H), 1.47 (dt, J = 14.7, 7.4 Hz, 2H), 1.37 (dd, J = 7.0, 1.3 Hz, 3H), 1.25 (dt, J = 5.7, 3.4 Hz, 2H), 1.22-1.12 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.0, 169.6, 149.8, 138.3, 129.0, 122.0, 52.4, 41.3, 31.9, 29.4, 29.22, 29.20, 23.9, 22.8, 21.3, 17.7, 14.2.

[0291] Example 9: Preparation of compound 7

[0292]

[0293] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 78 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 7 as a colourless oily liquid, with a yield of 85%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained for the hydrogen spectrum and carbon spectrum of the compound 7 obtained:

[0294] 1 H NMR (600 MHz, Chloroform-d) δ 7.07 (d, J = 8.7 Hz, 2H), 6.70 (d, J = 8.7 Hz, 2H), 3.64 (q, J = 7.0 Hz, 1H), 2.93 (s, 6H), 2.39-2.27 (m, 2H), 1.52-1.43 (m, 2H), 1.34 (d, J = 7.0 Hz, 3H), 1.26 (q, J = 7.4 Hz, 2H), 1.22-1.11 (m, 8H), 0.86 (t, J = 7.2 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 211.9, 149.7, 128.7, 113.1, 52.1, 40.9, 40.8, 31.9, 29.4, 29.3, 29.2, 24.1, 22.8, 17.5, 14.2.

[0295] Example 10: Preparation of compound 8

[0296]

[0297] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 79 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 8 as a colourless oily liquid, with a yield of 73% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 8 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0298] 1 H NMR (400 MHz, Chloroform-d) δ 7.12 (d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 3.69 (q, J = 6.9 Hz, 1H), 2.38-2.25 (m, 2H), 1.47 (q, J = 7.0 Hz, 2H), 1.35 (d, J = 7.0 Hz, 3H), 1.27-1.22 (m, 2H), 1.21-1.11 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.6, 158.8, 133.0, 129.0, 114.4, 55.4, 52.2, 41.0, 31.9, 29.4, 29.24, 29.22, 24.0, 22.8, 17.6, 14.2.

[0299] Example 11: Preparation of compound 9

[0300]

[0301] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 80 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 9 as a colorless oily liquid with a yield of 71% and an enantiomeric excess of 91% determined by high performance liquid chromatography. The obtained compound 9 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows:

[0302] 1 H NMR (400 MHz, Chloroform-d) δ 7.21 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 3.70 (q, J = 6.9 Hz, 1H), 2.47 (s, 3H), 2.33 (td, J = 7.5, 1.9 Hz, 2H), 1.52 - 1.40 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H), 1.28 - 1.22 (m, 2H), 1.22 - 1.11 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 137.7, 137.3, 128.5, 127.2, 52.5, 41.2, 31.9, 29.4, 29.23, 29.20, 24.0, 22.8, 17.6, 16.0, 14.2.

[0303] Example 12: Preparation of compound 10

[0304]

[0305] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 81 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 10 as a colourless oily liquid, with a yield of 72% and an enantiomeric excess of 92% determined by high performance liquid chromatography. The compound 10 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0306] 1 H NMR (400 MHz, Chloroform-d) δ 7.25 (t, J = 7.2 Hz, 2H), 7.20-7.17 (m, 1H), 7.14 (d, J = 6.7 Hz, 2H), 3.68 (q, J = 6.9 Hz, 1H), 2.26 (td, J = 7.5, 1.6 Hz, 2H), 1.44-1.35 (m, 2H), 1.31 (d, J = 6.9 Hz, 3H), 1.19-1.16 (m, 2H), 1.15-1.04 (m, 8H), 0.79 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 140.8, 128.9, 127.9, 127.1, 53.0, 41.1, 31.8, 29.3, 29.23, 29.19, 23.9, 22.6, 17.5, 14.1.

[0307] Example 13: Preparation of compound 11

[0308]

[0309] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 82 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 11 as a colourless oil, with a yield of 80% and an enantiomeric excess of 90% as determined by high performance liquid chromatography. The compound 11 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0310] 1 H NMR (400 MHz, Chloroform-d) δ 7.22 (d, J = 8.4 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 3.66 (q, J = 7.0 Hz, 1H), 2.26 (t, J = 7.3 Hz, 2H), 1.46-1.35 (m, 2H), 1.29 (d, J = 7.0 Hz, 3H), 1.22-1.15 (m, 4H), 1.15-1.04 (m, 8H), 0.79 (t, J = 6.8 Hz, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 210.7, 139.3, 133.1, 129.3, 129.1, 52.3, 41.3, 31.9, 29.4, 29.22, 29.16, 23.9, 22.8, 17.6, 14.2.

[0311] Example 14: Preparation of compound 12

[0312]

[0313] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 83 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was allowed to separate into layers, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 12 as a colourless oily liquid, with a yield of 76% and an enantiomeric excess of 90% as determined by high performance liquid chromatography. The compound 12 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0314] 1 H NMR (400 MHz, Chloroform-d) δ 7.44 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 3.71 (q, J = 7.0 Hz, 1H), 2.33 (t, J = 7.4 Hz, 2H), 1.53-1.42 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.26 (d, J = 5.3 Hz, 4H), 1.22-1.11 (m, 9H), 0.86 (t, J = 7.0 Hz, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 210.6, 139.8, 132.1, 129.7, 121.2, 52.4, 41.3, 31.9, 29.4, 29.22, 29.17, 23.9, 22.8, 17.6, 14.2.

[0315] Example 15: Preparation of compound 13

[0316]

[0317] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 84 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 13 as a colourless oily liquid, with a yield of 71% and an enantiomeric excess of 90% as determined by high performance liquid chromatography. The compound 13 obtained was subjected to1H,13C and19F spectroscopy and the results were as follows:

[0318] 1 H NMR (400 MHz, Chloroform-d) δ 7.58 (d, J = 7.9 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 3.83 (q, J = 7.0 Hz, 1H), 2.35 (t, J = 7.4 Hz, 2H), 1.52-1.45 (m, 2H), 1.40 (d, J = 6.9 Hz, 3H), 1.26-1.23 (m, 2H), 1.22-1.14 (m, 8H), 0.85 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.3, 144.8 (d, J = 1.6 Hz), 129.5 (q, J = 32.5 Hz), 128.4, 125.9 (q, J = 3.8 Hz), 124.2 (d, J = 272.1 Hz), 52.8, 41.5, 31.9, 29.4, 29.21, 29.16, 23.9, 22.7, 17.7, 14.2. 19 F NMR (377 MHz, Chloroform-d) δ -62.54.

[0319] Example 16: Preparation of compound 14

[0320]

[0321] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 85 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 14 as a colourless oil, with a yield of 78% and an enantiomeric excess of 90% as determined by high performance liquid chromatography. The compound 14 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0322] 1H NMR (400 MHz, Chloroform-d) δ 7.91 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 3.82 (q, J = 7.0 Hz, 1H), 2.58 (s, 3H), 2.34 (t, J = 7.4 Hz, 2H), 1.52-1.45 (m, 2H), 1.40 (d, J = 7.0 Hz, 3H), 1.25-1.22 (m, 2H), 1.20-1.11 (m, 8H), 0.84 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.3, 197.8, 146.2, 136.2, 129.1, 128.3, 53.0, 41.5, 31.9, 29.4, 29.2, 29.1, 26.7, 23.9, 22.7, 17.5, 14.2.

[0323] Example 17: Preparation of compound 15

[0324]

[0325] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 15 as a colourless oily liquid, with a yield of 81% and an enantiomeric excess of 93% as determined by high performance liquid chromatography. The compound 15 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0326] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H), 3.81 (q, J = 7.0 Hz, 1H), 2.33 (t, J = 7.4 Hz, 2H), 1.52-1.42 (m, 2H), 1.39 (d, J = 6.9 Hz, 3H), 1.27-1.20 (m, 2H), 1.20-1.08 (m, 8H), 0.84 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.4, 166.9, 146.0, 130.3, 129.2, 128.1, 53.0, 52.3, 41.4, 31.9, 29.4, 29.2, 29.1, 23.9, 22.7, 17.5, 14.2.

[0327] Example 18: Preparation of compound 16

[0328]

[0329] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 87 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 16 as a colourless oil, with a yield of 52% and an enantiomeric excess of 83% as determined by high performance liquid chromatography. The compound 16 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0330] 1 H NMR (400 MHz, Chloroform-d) δ 7.62 (d, J = 8.3 Hz, 2H), 7.33 (d, J = 8.3 Hz, 2H), 3.83 (q, J = 7.0 Hz, 1H), 2.35 (td, J = 7.3, 4.2 Hz, 2H), 1.52 - 1.44 (m, 2H), 1.40 (d, J = 7.0 Hz, 3H), 1.29 - 1.23 (m, 2H), 1.22 - 1.12 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 209.6, 146.0, 132.6, 128.7, 118.6, 111.1, 52.8, 41.6, 31.8, 29.3, 29.1, 29.0, 23.7, 22.6, 17.5, 14.1.

[0331] Example 19: Preparation of compound 17

[0332]

[0333] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 88 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 17 as a colorless oily liquid with a yield of 85%, an enantiomeric excess of 90% determined by high performance liquid chromatography, and the following results were obtained by1H NMR and13C NMR detection of the obtained compound 17:

[0334] 1 H NMR (600 MHz, Chloroform-d) δ 7.21 (t, J = 7.6 Hz, 1H), 7.06 (d, J = 7.4 Hz, 1H), 7.00 (d, J = 8.0 Hz, 2H), 3.71 (q, J = 6.9 Hz, 1H), 2.37-2.29 (m, 5H), 1.52-1.43 (m, 2H), 1.37 (d, J = 6.9 Hz, 3H), 1.28-1.25 (m, 2H), 1.21-1.11 (m, 8H), 0.86 (t, J = 7.2 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 211.4, 140.9, 138.7, 128.9, 128.7, 128.0, 125.1, 53.0, 41.2, 31.9, 29.4, 29.23, 29.21, 24.0, 22.8, 21.5, 17.6, 14.2.

[0335] Example 20: Preparation of compound 18

[0336]

[0337] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 89 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 18 as a colorless oily liquid with a yield of 77%, an enantiomeric excess of 90% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 18:

[0338] 1 H NMR (400 MHz, Chloroform-d) δ 7.31-7.26 (m, 1H), 7.03-6.89 (m, 3H), 3.75 (q, J = 7.0 Hz, 1H), 2.35 (t, J = 7.6 Hz, 2H), 1.54-1.43 (m, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.28-1.23 (m, 2H), 1.22-1.12 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.5, 163.2 (d, J = 246.6 Hz), 143.3 (d, J = 7.0 Hz), 130.4 (d, J = 8.3 Hz), 123.7 (d, J = 2.9 Hz), 114.9 (d, J = 21.5 Hz), 114.1 (d, J = 21.0 Hz), 52.7 (d, J = 1.7 Hz), 41.3, 31.9, 29.4, 29.22, 29.18, 23.9, 22.8, 17.5, 14.2 19 F NMR (376 MHz, Chloroform-d) δ -112.54.

[0339] Example 21: Preparation of compound 19

[0340]

[0341] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 90 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 19 as a colourless oily liquid, with a yield of 90% and an enantiomeric excess of 90% as determined by high performance liquid chromatography. The compound 19 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0342] 1 H NMR (400 MHz, Chloroform-d) δ 7.22-7.12 (m, 3H), 7.02 (d, J = 6.9 Hz, 1H), 3.65 (q, J = 6.8 Hz, 1H), 2.27 (t, J = 7.3 Hz, 2H), 1.45-1.38 (m, 2H), 1.30 (d, J = 6.8 Hz, 3H), 1.19-1.16 (m, 2H), 1.15-1.05 (m, 8H), 0.78 (t, J = 6.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.4, 142.8, 134.8, 130.2, 128.2, 127.4, 126.2, 52.6, 41.3, 31.9, 29.4, 29.21, 29.16, 23.9, 22.7, 17.6, 14.2.

[0343] Example 22: Preparation of compound 20

[0344]

[0345] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 91 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 20 as a colourless oil, with a yield of 67% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 20 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0346] 1 H NMR (400 MHz, Chloroform-d) δ 7.35 (t, J = 7.9 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 7.13-7.09 (m, 1H), 7.07 (s, 1H), 3.77 (q, J = 7.0 Hz, 1H), 2.35 (t, J = 7.4 Hz, 2H), 1.52-1.44 (m, 2H), 1.39 (d, J = 7.0 Hz, 3H), 1.27-1.23 (m, 2H), 1.22-1.12 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 210.3, 149.7, 143.1, 130.3, 126.4, 120.7, 120.6 (q, J = 257.2 Hz), 119.6, 52.7, 41.4, 31.9, 29.4, 29.19, 29.15, 23.9, 22.7, 17.6, 14.2. 19 F NMR (377 MHz, Chloroform-d) δ -57.80.

[0347] Example 23: Preparation of compound 21

[0348]

[0349] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 92 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 21 as a colourless oily liquid, with a yield of 87% and an enantiomeric excess of 92% determined by high performance liquid chromatography. The compound 21 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0350] 1 H NMR (400 MHz, Chloroform-d) δ 7.59 (d, J = 7.8 Hz, 1H), 7.30-7.25 (m, 1H), 7.15-7.08 (m, 2H), 4.30 (q, J = 6.9 Hz, 1H), 2.35 (td, J = 7.2, 3.2 Hz, 2H), 1.56-1.47 (m, 2H), 1.35 (d, J = 6.9 Hz, 3H), 1.27-1.23 (m, 2H), 1.23-1.16 (m, 8H), 0.86 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.6, 140.4, 133.3, 128.8, 128.7, 128.1, 125.0, 51.5, 41.7, 31.9, 29.4, 29.22, 29.20, 24.0, 22.8, 16.9, 14.2.

[0351] Example 24: Preparation of compound 22

[0352]

[0353] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 93 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 22 as a colourless oily liquid, with a yield of 83% and an enantiomeric excess of 89% as determined by high performance liquid chromatography. The compound 22 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0354] 1 H NMR (400 MHz, Chloroform-d) δ 7.06-6.97 (m, 2H), 6.90 (s, 1H), 3.70 (q, J = 6.9 Hz, 1H), 3.14 (s, 3H), 2.38-2.30 (m, 2H), 1.52-1.43 (m, 2H), 1.35 (d, J = 6.9 Hz, 3H), 1.26-1.23 (m, 2H), 1.22-1.12 (m, 8H), 0.86 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.6, 146.5, 144.7, 139.6, 126.7, 123.0, 122.1, 53.5, 41.1, 31.9, 29.5, 29.4, 29.24, 29.19, 24.0, 22.8, 17.9, 14.2.

[0355] Example 25: Preparation of compound 23

[0356]

[0357] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 94 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 23 as a colourless oily liquid, with a yield of 80% and an enantiomeric excess of 88% as determined by high performance liquid chromatography. The compound 23 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0358] 1 H NMR (400 MHz, Chloroform-d) δ 7.30 (d, J = 7.9 Hz, 1H), 6.78-6.73 (m, 2H), 3.88 (s, 3H), 3.72 (q, J = 7.0 Hz, 1H), 2.43-2.27 (m, 2H), 1.54-1.43 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.25 (d, J = 5.4 Hz, 2H), 1.22-1.12 (m, 8H), 0.85 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.8, 155.3, 140.9, 130.5, 121.4, 121.0, 111.4, 56.3, 52.8, 41.3, 31.9, 29.4, 29.23, 29.18, 23.9, 22.8, 17.7, 14.2.

[0359] Example 26: Preparation of compound 24

[0360]

[0361] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 95 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 24 as a colourless oil, with a yield of 86% and an enantiomeric excess of 83% as determined by high performance liquid chromatography. The compound 24 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0362] 1 H NMR (600 MHz, Chloroform-d) δ 7.00 (d, J = 8.2 Hz, 1H), 6.97-6.89 (m, 2H), 3.74 (q, J = 7.0 Hz, 1H), 2.36 (t, J = 7.4 Hz, 2H), 1.53-1.45 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.27-1.23 (m, 2H), 1.22-1.14 (m, 8H), 0.86 (t, J = 7.1 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 210.4, 144.1, 142.8, 136.9, 131.6 (t, J = 255.2 Hz), 123.1, 109.6, 109.0, 52.4, 41.2, 31.8, 29.3, 29.22, 29.19, 23.8, 22.6, 17.8, 14.0. 19 F NMR (377 MHz, Chloroform-d) δ -49.96.

[0363] Example 27: Preparation of compound 25

[0364]

[0365] Under a nitrogen atmosphere, Ni(OAc)₂·4H₂O (0.01 mmol), ligand L15 (0.012 mmol), and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min. Then, compound 96 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e., compound 71) (0.20 mmol), and NaHCO₃ (0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, followed by the dropwise addition of trimethoxysilane (0.40 mmol). The reaction mixture was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 hours. After the reaction was complete, the mixture was diluted with 5 mL of water and 5 mL of ethyl acetate. After the reaction mixture separated into layers, the aqueous phase was extracted twice with ethyl acetate (5 mL × 2). The organic phases were then combined and washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, and purified by column chromatography to obtain a colorless oily liquid compound 25 in 52% yield. The enantiomeric excess was determined to be 92% by high performance liquid chromatography. Compound 25 was subjected to 1H NMR and 1C NMR spectroscopy, and the results are as follows:

[0366] 1 H NMR (400MHz,Chloroform-d)δ8.25(s,1H),7.49(s,1H),7.35(d,J=8.4Hz,1H),7.21(t,J=2.7Hz,1H),7.03(dd,J=8.4,1.8Hz,1H),6.60-6.47(m,1H) ,3.84(q,J=6.9Hz,1H),2.43-2.30(m,2H),1.57-1.45(m,2H),1.44(d,J= 7.0Hz,3H),1.29-1.22(m,2H),1.20-1.10(m,8H),0.85(t,J=7.0Hz,3H). 13 C NMR (101MHz,Chloroform-d)δ212.3,135.1,132.4,128.4,124.9,122.1,120.0,111.6,102.6,53.1,41.0,31.9,29.4,29.2,24.1,22.7,18.0,14.2.

[0367] Example 28: Preparation of Compound 26

[0368]

[0369] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 97 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere, stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used for separation and purification to obtain compound 26 as a colorless oily liquid, with a yield of 84%, an enantiomeric excess of 94% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 26:

[0370] 1 H NMR (400 MHz, Chloroform-d) δ 7.24 (t, J = 7.2 Hz, 2H), 7.19-7.15 (m, 1H), 7.15-7.10 (m, 2H), 3.45 (t, J = 7.4 Hz, 1H), 2.31-2.23 (m, 2H), 2.04-1.92 (m, 1H), 1.67-1.58 (m, 1H), 1.46-1.34 (m, 2H), 1.19-1.16 (m, 2H), 1.15-1.04 (m, 8H), 0.81-0.73 (m, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 211.0, 139.2, 128.9, 128.4, 127.2, 60.9, 42.1, 31.9, 29.4, 29.23, 29.18, 25.4, 23.9, 22.8, 14.2, 12.3.

[0371] Example 29: Preparation of compound 27

[0372]

[0373] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 98 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 27 as a colourless oil, with a yield of 82% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 27 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0374] 1 H NMR (400 MHz, Chloroform-d) δ 7.13 (d, J = 8.7 Hz, 2H), 6.87 (d, J = 8.7 Hz, 2H), 3.81 (s, 3H), 3.48 (t, J = 7.4 Hz, 1H), 2.42-2.29 (m, 2H), 2.07-1.97 (m, 1H), 1.72-1.68 (m, 1H), 1.53-1.43 (m, 2H), 1.30-1.25 (m, 2H), 1.24-1.14 (m, 8H), 0.88 (t, J = 7.0 Hz, 3H), 0.83 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 158.8, 131.3, 129.4, 114.3, 60.0, 55.3, 41.9, 31.9, 29.4, 29.24, 29.20, 25.4, 23.9, 22.8, 14.2, 12.2.

[0375] Example 30: Preparation of compound 28

[0376]

[0377] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 99 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 28 as a colourless oil, with a yield of 75% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 28 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0378] 1 H NMR (400 MHz, Chloroform-d) δ 7.28 (d, J = 8.5 Hz, 2H), 7.14 (d, J = 8.4 Hz, 2H), 3.50 (t, J = 7.4 Hz, 1H), 2.33 (t, J = 7.1 Hz, 2H), 2.07-1.97 (m, 1H), 1.71-1.64 (m, 1H), 1.52-1.44 (m, 2H), 1.27-1.23 (m, 2H), 1.21-1.10 (m, 8H), 0.86 (t, J = 6.9 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.6, 137.7, 133.1, 129.7, 129.1, 60.2, 42.2, 31.9, 29.4, 29.22, 29.16, 25.5, 23.8, 22.8, 14.2, 12.2.

[0379] Example 31 : Preparation of compound 29

[0380]

[0381] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 100 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 29 as a colourless oil, with a yield of 88% and an enantiomeric excess of 93% as determined by high performance liquid chromatography. The compound 29 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0382] 1 H NMR (400 MHz, Chloroform-d) δ 7.31 (t, J = 7.3 Hz, 2H), 7.26-7.23 (m, 1H), 7.20 (d, J = 6.8 Hz, 2H), 3.62 (t, J = 7.4 Hz, 1H), 2.38-2.29 (m, 2H), 2.05-1.94 (m, 1H), 1.72-1.66 (m, 1H), 1.52-1.41 (m, 2H), 1.31-1.22 (m, 4H), 1.20-1.13 (m, 8H), 0.87 (dt, J = 9.6, 7.2 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 211.0, 139.4, 128.9, 128.4, 127.2, 58.9, 42.0, 34.4, 31.9, 29.4, 29.21, 29.16, 23.9, 22.8, 20.8, 14.2, 14.1.

[0383] Example 32: Preparation of compound 30

[0384]

[0385] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 101 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 30 as a colorless oily liquid with a yield of 88%, an enantiomeric excess of 94% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 30:

[0386] 1 H NMR (400 MHz, Chloroform-d) δ 7.31 (t, J = 7.2 Hz, 2H), 7.26-7.23 (m, 1H), 7.20 (d, J = 6.8 Hz, 2H), 3.60 (t, J = 7.4 Hz, 1H), 2.36-2.30 (m, 2H), 2.07-1.96 (m, 1H), 1.72-1.65 (m, 1H), 1.52-1.41 (m, 2H), 1.31-1.23 (m, 6H), 1.19-1.12 (m, 8H), 0.87-0.82 (m, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 139.5, 128.9, 128.4, 127.2, 59.2, 42.0, 32.0, 31.9, 29.9, 29.4, 29.22, 29.16, 23.9, 22.9, 22.8, 14.2, 14.1.

[0387] Example 33: Preparation of compound 31

[0388]

[0389] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 102 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 31 as a colourless oil, with a yield of 93% and an enantiomeric excess of 95% as determined by high performance liquid chromatography. The compound 31 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0390] 1 H NMR (600 MHz, Chloroform-d) δ 7.31 (t, J = 7.5 Hz, 2H), 7.24 (t, J = 7.3 Hz, 1H), 7.20 (d, J = 7.6 Hz, 2H), 3.60 (t, J = 7.4 Hz, 1H), 2.39-2.29 (m, 2H), 2.04-1.97 (m, 1H), 1.69-1.64 (m, 1H), 1.51-1.42 (m, 2H), 1.31-1.21 (m, 8H), 1.20-1.11 (m, 10H), 0.88-0.82 (m, 6H). 13 C NMR (151 MHz, Chloroform-d) δ 211.1, 139.5, 128.9, 128.4, 127.2, 59.2, 42.0, 32.3, 31.9, 31.8, 29.4, 29.4, 29.22, 29.17, 27.7, 23.9, 22.8, 22.7, 14.22, 14.19.

[0391] Example 34: Preparation of compound 32

[0392]

[0393] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 103 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 32 as a colorless oily liquid, with a yield of 83%, an enantiomeric excess of 88% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 32:

[0394] 1 H NMR (600 MHz, Chloroform-d) δ 7.40-7.26 (m, 7H), 7.26-7.23 (m, 1H), 7.20 (d, J = 7.5 Hz, 2H), 4.42 (d, J = 3.6 Hz, 2H), 3.92 (t, J = 7.4 Hz, 1H), 3.47-3.40 (m, 1H), 3.33-3.25 (m, 1H), 2.41-2.36 (m, 1H), 2.36-2.29 (m, 2H), 1.96-1.89 (m, 1H), 1.49-1.39 (m, 2H), 1.29-1.22 (m, 3H), 1.21-1.08 (m, 8H), 0.86 (t, J = 7.2 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 210.6, 138.9, 138.5, 129.0, 128.6, 128.5, 127.9, 127.7, 127.3, 73.1, 67.8, 55.2, 42.1, 32.3, 31.9, 29.4, 29.22, 29.15, 23.8, 22.8, 14.2.

[0395] Example 35: Preparation of compound 33

[0396]

[0397] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 104 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 33 as a colourless oil, with a yield of 74% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 33 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0398] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H), 3.81 (q, J = 6.9 Hz, 1H), 2.33 (t, J = 7.4 Hz, 2H), 1.53-1.43 (m, 2H), 1.39 (d, J = 7.0 Hz, 3H), 1.24-1.18 (m, 2H), 1.18-1.09 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.4, 167.0, 146.0, 130.3, 129.2, 128.1, 53.0, 52.3, 41.5, 31.6, 28.8, 23.9, 22.6, 17.5, 14.1.

[0399] Example 36: Preparation of compound 34

[0400]

[0401] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 105 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 34 as a colorless oily liquid, with a yield of 73%, an enantiomeric excess of 93% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 34:

[0402] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H), 3.81 (q, J = 7.0 Hz, 1H), 2.32 (t, J = 7.2 Hz, 2H), 1.52-1.37 (m, 6H), 1.05-0.98 (m, 2H), 0.80 (dd, J = 6.6, 2.6 Hz, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 210.4, 167.0, 146.0, 130.3, 129.2, 128.1, 53.0, 52.3, 41.7, 38.4, 27.9, 22.6, 22.5, 21.7, 17.5.

[0403] Example 37: Preparation of compound 35

[0404]

[0405] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 106 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 35 as a colourless oil, in a yield of 87%, with an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 35 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0406] 1 H NMR (400 MHz, Chloroform-d) δ 7.26 (d, J = 8.4 Hz, 2H), 7.06 (d, J = 8.3 Hz, 2H), 3.65 (q, J = 7.0 Hz, 1H), 2.25 (ddd, J = 12.0, 8.2, 4.2 Hz, 2H), 1.58 - 1.50 (m, 5H), 1.39 (dddd, J = 15.0, 7.8, 6.7, 2.0 Hz, 2H), 1.29 (d, J = 7.0 Hz, 3H), 1.23 (s, 9H), 1.12 - 1.01 (m, 4H), 0.98 - 0.92 (m, 2H), 0.76 - 0.66 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.5, 150.0, 137.7, 127.6, 125.8, 52.6, 41.4, 37.5, 36.9, 34.6, 33.4, 33.3, 31.5, 26.8, 26.4, 21.4, 17.5.

[0407] Example 38: Preparation of compound 36

[0408]

[0409] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 107 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 36 as a colourless oily liquid, with a yield of 76% and an enantiomeric excess of 92% determined by high performance liquid chromatography. The compound 36 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0410] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H), 3.82 (q, J = 7.0 Hz, 1H), 2.37-2.31 (m, 2H), 1.64-1.47 (m, 5H), 1.39 (d, J = 7.0 Hz, 3H), 1.38-1.31 (m, 2H), 1.16-1.00 (m, 4H), 0.83-0.70 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 210.6, 167.0, 146.0, 130.3, 129.2, 128.1, 53.1, 52.3, 39.0, 37.2, 33.3, 33.0, 31.3, 26.6, 26.31, 26.29, 17.5.

[0411] Example 39: Preparation of compound 37

[0412]

[0413] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 108 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 37 as a colourless oily liquid, with a yield of 81% and an enantiomeric excess of 89% as determined by high performance liquid chromatography. The compound 37 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0414] 1 H NMR (400 MHz, Chloroform-d) δ 7.93 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 8.5 Hz, 2H), 3.93 (d, J = 11.4 Hz, 2H), 3.84 (s, 3H), 3.75 (q, J = 6.9 Hz, 1H), 2.48 (q, J = 13.6 Hz, 2H), 2.30 (t, J = 7.4 Hz, 2H), 1.34 (d, J = 12.5 Hz, 16H), 1.17-1.11 (m, 1H), 0.96-0.82 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 209.9, 166.8, 154.9, 145.8, 130.3, 129.3, 128.0, 79.3, 53.2, 52.3, 49.3, 38.4, 35.4, 32.1, 31.8, 30.2, 28.5, 17.4..

[0415] Example 40: Preparation of compound 38

[0416]

[0417] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 86 (0.10 mmol), compound 109 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 38 as a colourless oily liquid, with a yield of 79% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 38 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0418] 1 H NMR (400 MHz, Chloroform-d) δ 7.99 (d, J = 8.3 Hz, 2H), 7.28 (d, J = 8.3 Hz, 2H), 3.90 (s, 3H), 3.81 (q, J = 6.9 Hz, 1H), 3.51 (t, J = 6.8 Hz, 2H), 2.33 (t, J = 7.3 Hz, 2H), 1.78-1.71 (m, 2H), 1.50-1.43 (m, 2H), 1.39 (d, J = 7.0 Hz, 5H), 1.29-1.22 (m, 4H), 1.17 (d, J = 13.4 Hz, 8H). 13 C NMR (101 MHz, Chloroform-d) δ 210.3, 166.9, 146.0, 130.3, 129.2, 128.1, 53.0, 52.3, 45.3, 41.4, 32.7, 29.6, 29.5, 29.4, 29.3, 29.1, 29.0, 27.0, 23.9, 17.5.

[0419] Example 41: Preparation of compound 39

[0420]

[0421] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 110 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 39 as a colourless oil, in 82% yield with an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 39 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0422] 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.3 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 3.72 (q, J = 7.0 Hz, 1H), 3.40 (t, J = 6.9 Hz, 2H), 2.34 (td, J = 7.4, 3.1 Hz, 2H), 1.84 (p, J = 6.9 Hz, 2H), 1.48 (h, J = 6.7 Hz, 2H), 1.41 (d, J = 6.9 Hz, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.31 (s, 9H), 1.26 (s, 4H), 1.23-1.12 (m, 8H). 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 149.9, 137.6, 127.5, 125.7, 52.4, 41.0, 34.4, 34.0, 32.8, 31.4, 29.6, 29.5, 29.4, 29.3, 29.1, 28.7, 28.2, 23.9, 17.4.

[0423] Example 42: Preparation of compound 40

[0424]

[0425] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 111 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 40 as a colorless oily liquid, with a yield of 87%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 40:

[0426] 1 H NMR (400 MHz, Chloroform-d) δ 8.12 (d, J = 7.7 Hz, 2H), 7.48 (t, J = 7.7 Hz, 2H), 7.39 (d, J = 8.2 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.25 (t, J = 7.2 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 4.27 (t, J = 7.2 Hz, 2H), 3.70 (q, J = 7.0 Hz, 1H), 2.39-2.25 (m, 2H), 1.87-1.78 (m, 2H), 1.52-1.43 (m, 2H), 1.38 (d, J = 7.0 Hz, 3H), 1.34-1.26 (m, 11H), 1.24-1.16 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 150.1, 140.5, 137.6, 127.6, 125.9, 125.7, 122.9, 120.4, 118.8, 108.7, 52.5, 43.0, 40.8, 34.5, 31.4, 28.8, 27.1, 23.7, 17.5.

[0427] Example 43: Preparation of compound 41

[0428]

[0429] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 112 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 41 as a colorless oily liquid with a yield of 83%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 41:

[0430] 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 7.8 Hz, 1H), 7.24 (t, J = 7.5 Hz, 3H), 7.11 (t, J = 7.6 Hz, 1H), 7.02 (dd, J = 7.7, 5.7 Hz, 3H), 6.97 (d, J = 3.1 Hz, 1H), 6.39 (d, J = 2.9 Hz, 1H), 3.98 (t, J = 7.1 Hz, 2H), 3.61 (q, J = 6.9 Hz, 1H), 2.24 (q, J = 7.0 Hz, 2H), 1.68 (p, J = 7.2 Hz, 2H), 1.43 - 1.36 (m, 2H), 1.28 (d, J = 6.9 Hz, 3H), 1.22 (s, 9H), 1.18 - 1.05 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 150.0, 137.5, 135.9, 128.6, 127.8, 127.5, 125.8, 121.3, 120.9, 119.2, 109.4, 100.9, 52.5, 46.3, 40.8, 34.5, 31.4, 30.0, 28.6, 26.7, 23.6, 17.4.

[0431] Example 44: Preparation of compound 42

[0432]

[0433] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 113 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 42 as a colorless oily liquid, with a yield of 88%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 42:

[0434] 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 3.71 (q, J = 6.9 Hz, 1H), 3.64 (s, 3H), 2.39-2.29 (m, 2H), 2.24 (t, J = 7.6 Hz, 2H), 1.58-1.45 (m, 4H), 1.36 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.24-1.12 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 174.2, 149.9, 137.5, 127.5, 125.8, 52.5, 51.5, 40.8, 34.4, 34.0, 31.3, 28.8, 28.6, 24.7, 23.6, 17.4.

[0435] Example 45: Preparation of compound 43

[0436]

[0437] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 114 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 43 as a colorless oily liquid, with a yield of 87%, an enantiomeric excess of 91% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 43:

[0438] 1 H NMR (400 MHz, Chloroform-d) δ 7.82 (dd, J = 5.4, 3.0 Hz, 2H), 7.69 (dd, J = 5.5, 3.0 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 3.71 (q, J = 6.9 Hz, 1H), 3.67-3.61 (m, 2H), 2.32 (td, J = 7.5, 2.4 Hz, 2H), 1.67-1.58 (m, 2H), 1.50-1.40 (m, 2H), 1.35 (d, J = 7.0 Hz, 3H), 1.29 (s, 9H), 1.27-1.22 (m, 3H), 1.20-1.10 (m, 4H).

[0439] 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 168.5, 150.0, 137.7, 133.9, 132.3, 127.6, 125.8, 123.2, 52.5, 41.0, 38.1, 34.5, 31.4, 29.3, 29.1, 29.0, 28.6, 26.9, 23.9, 17.5.

[0440] Example 46: Preparation of compound 44

[0441]

[0442] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 115 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 44 as a colourless oily liquid, with a yield of 91% and an enantiomeric excess of 92% determined by high performance liquid chromatography. The compound 44 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0443] 1 H NMR (400 MHz, Chloroform-d) δ 7.73 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 7.9 Hz, 2H), 7.11 (d, J = 8.4 Hz, 2H), 4.64 (t, J = 6.2 Hz, 1H), 3.70 (q, J = 7.0 Hz, 1H), 2.89-2.82 (m, 2H), 2.41 (s, 3H), 2.31 (td, J = 7.5, 3.2 Hz, 2H), 1.45-1.36 (m, 4H), 1.35 (d, J = 7.0 Hz, 3H), 1.29 (s, 9H), 1.19-1.05 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 150.1, 143.4, 137.6, 137.0, 129.8, 127.6, 127.2, 125.9, 52.5, 43.2, 40.8, 34.5, 31.4, 29.4, 28.5, 26.3, 23.6, 21.6, 17.5.

[0444] Example 47: Preparation of compound 45

[0445]

[0446] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 116 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere, stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 45 as a colorless oily liquid, with a yield of 95%, dr = 1:1, and an enantiomeric excess of 91% / 91% determined by high performance liquid chromatography. The obtained compound 45 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.26 (d, J = 8.3 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 4.47 (dd, J = 4.6, 2.7 Hz, 1H), 3.82-3.74 (m, 1H), 3.68-3.57 (m, 2H), 3.45-3.37 (m, 1H), 3.26 (dt, J = 9.6, 6.6 Hz, 1H), 2.28 (td, J = 7.4, 2.8 Hz, 2H), 1.79-1.71 (m, 1H), 1.65-1.60 (m, 1H), 1.53-1.37 (m, 9H), 1.29 (d, J = 6.9 Hz, 3H), 1.23 (s, 9H), 1.21-1.16 (m, 2H), 1.15-1.07 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 149.9, 137.6, 127.5, 125.7, 98.8, 67.5, 62.4, 52.4, 40.9, 34.4, 31.4, 30.8, 29.5, 28.9, 26.0, 25.5, 23.8, 19.7, 17.4.

[0447] Example 48: Preparation of compound 46

[0448]

[0449] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 117 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 46 as a colourless oily liquid, with a yield of 85% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 46 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0450] 1 H NMR (400 MHz, Chloroform-d) δ 7.37-7.30 (m, 6H), 7.29-7.26 (m, 1H), 7.13 (d, J = 8.3 Hz, 2H), 4.48 (s, 2H), 3.72 (q, J = 7.0 Hz, 1H), 3.42 (t, J = 6.6 Hz, 2H), 2.35 (td, J = 7.5, 3.0 Hz, 2H), 1.59-1.46 (m, 4H), 1.37 (d, J = 6.9 Hz, 3H), 1.31 (s, 9H), 1.30-1.23 (m, 2H), 1.21-1.13 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 150.0, 138.8, 137.7, 128.5, 127.7, 127.6, 125.9, 73.0, 70.4, 52.5, 41.0, 34.6, 31.5, 29.7, 29.0, 26.0, 23.9, 17.5.

[0451] Example 49: Preparation of compound 47

[0452]

[0453] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 118 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 47 as a colourless oily liquid, with a yield of 81% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 47 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0454] 1 H NMR (600 MHz, Chloroform-d) δ 7.32 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 3.99 (t, J = 6.8 Hz, 2H), 3.71 (q, J = 7.0 Hz, 1H), 2.40-2.30 (m, 2H), 2.01 (s, 3H), 1.56-1.51 (m, 2H), 1.51-1.44 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.26-1.22 (m, 2H), 1.20-1.13 (m, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 211.3, 171.3, 150.1, 137.6, 127.6, 125.9, 64.6, 52.6, 40.9, 34.5, 31.4, 28.7, 28.5, 25.7, 23.8, 21.1, 17.5.

[0455] Example 50: Preparation of compound 48

[0456]

[0457] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 119 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 48 as a colourless oily liquid, with a yield of 82% and an enantiomeric excess of 93% as determined by high performance liquid chromatography. The compound 48 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectroscopy, and the results were as follows:

[0458] 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.3 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 3.72 (q, J = 7.0 Hz, 1H), 3.54 (t, J = 6.6 Hz, 2H), 2.35 (td, J = 7.5, 2.7 Hz, 2H), 1.51 - 1.40 (m, 4H), 1.37 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.26 - 1.14 (m, 4H), 0.88 (s, 9H), 0.02 (s, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 211.5, 150.1, 137.7, 127.6, 125.9, 63.3, 52.6, 41.1, 34.6, 32.8, 31.5, 29.0, 26.1, 25.7, 24.0, 18.5, 17.5, -5.1.

[0459] Example 51: Preparation of compound 49

[0460]

[0461] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 120 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 49 as a colorless oily liquid with a yield of 84%, an enantiomeric excess of 91% determined by high performance liquid chromatography, and the following results were obtained by1H NMR,13C NMR and X-ray diffraction detection of the obtained compound 49:

[0462] 1 H NMR (400 MHz, Chloroform-d) δ 7.91 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.3 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.99 (t, J = 6.5 Hz, 2H), 3.72 (q, J = 6.9 Hz, 1H), 2.54 (s, 3H), 2.40-2.29 (m, 2H), 1.79-1.74 (m, 2H), 1.53-1.44 (m, 2H), 1.44-1.38 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.27-1.14 (m, 5H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 196.8, 163.1, 149.9, 137.6, 130.6, 130.1, 127.5, 125.7, 114.1, 68.2, 52.4, 41.0, 34.4, 31.3, 29.3, 29.2, 29.1, 29.0, 26.3, 25.9, 23.8, 17.4.

[0463]

[0464] Example 52: Preparation of compound 50

[0465]

[0466] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 121 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 50 as a colorless oily liquid, with a yield of 71%, an enantiomeric excess of 91% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 50:

[0467] 1 H NMR (400 MHz, Chloroform-d) δ 7.80-7.70 (m, 3H), 7.44 (t, J = 7.3 Hz, 1H), 7.39-7.30 (m, 3H), 7.21-7.10 (m, 4H), 4.03 (t, J = 6.5 Hz, 2H), 3.74 (q, J = 6.9 Hz, 1H), 2.45-2.34 (m, 2H), 1.83-1.75 (m, 2H), 1.60-1.52 (m, 2H), 1.45-1.43 (m, 1H), 1.39 (d, J = 7.0 Hz, 3H), 1.32 (s, 9H), 1.29-1.22 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 157.1, 150.1, 137.6, 134.7, 129.4, 129.0, 127.7, 127.6, 126.8, 126.4, 125.9, 123.6, 119.1, 106.6, 67.9, 52.6, 40.9, 34.6, 31.5, 29.1, 28.9, 25.9, 23.9, 17.5.

[0468] Example 53: Preparation of compound 51

[0469]

[0470] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 122 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 51 as a colorless oily liquid with a yield of 84%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 51:

[0471] 1 H NMR (400 MHz, Chloroform-d) δ 7.33 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.3 Hz, 2H), 6.69 (d, J = 8.5 Hz, 1H), 6.46 (d, J = 2.5 Hz, 1H), 6.29 (dd, J = 8.5, 2.5 Hz, 1H), 5.90 (s, 2H), 3.82 (t, J = 6.5 Hz, 2H), 3.73 (q, J = 7.0 Hz, 1H), 2.44-2.30 (m, 2H), 1.71-1.65 (m, 2H), 1.56-1.46 (m, 2H), 1.37 (d, J = 7.0 Hz, 3H), 1.35-1.33 (m, 1H), 1.30 (s, 9H), 1.26-1.17 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 154.6, 150.0, 148.2, 141.4, 137.5, 127.5, 125.8, 107.9, 105.6, 101.1, 98.0, 68.7, 52.5, 40.8, 34.5, 31.4, 29.1, 28.8, 25.8, 23.7, 17.4.

[0472] Example 54: Preparation of compound 52

[0473]

[0474] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 123 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 52 as a colourless oily liquid, with a yield of 90% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 52 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0475] 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 3.72 (q, J = 6.9 Hz, 1H), 2.34 (td, J = 7.4, 2.6 Hz, 2H), 1.55-1.45 (m, 3H), 1.44-1.38 (m, 2H), 1.36 (d, J = 6.9 Hz, 3H), 1.30 (s, 9H), 1.28-1.22 (m, 2H), 1.21-1.15 (m, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 149.9, 137.6, 127.5, 125.7, 71.0, 52.4, 43.9, 41.0, 34.4, 31.4, 29.9, 29.2, 29.0, 24.1, 23.8, 17.4.

[0476] Example 55: Preparation of compound 53

[0477]

[0478] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 124 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 53 as a colourless oily liquid, with a yield of 88% and an enantiomeric excess of 91% as determined by high performance liquid chromatography. The compound 53 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0479] 1 H NMR (400 MHz, Chloroform-d) δ 8.03 (d, J = 6.9 Hz, 2H), 7.55 (t, J = 7.4 Hz, 1H), 7.46-7.41 (m, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 4.26 (t, J = 6.6 Hz, 2H), 3.72 (q, J = 6.9 Hz, 1H), 2.43-2.29 (m, 2H), 1.71-1.64 (m, 2H), 1.56-1.45 (m, 2H), 1.40-1.33 (m, 5H), 1.30 (s, 9H), 1.27-1.20 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.3, 166.8, 150.1, 137.6, 132.9, 130.6, 129.6, 128.4, 127.6, 125.9, 65.0, 52.6, 40.9, 34.5, 31.4, 28.8, 28.6, 25.9, 23.8, 17.5.

[0480] Example 56: Preparation of compound 54

[0481]

[0482] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 125 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 54 as a colourless oily liquid, with a yield of 81% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 54 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0483] 1 H NMR (400 MHz, Chloroform-d) δ 7.88 (d, J = 8.6 Hz, 2H), 7.32 (d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 7.05 (d, J = 8.3 Hz, 2H), 4.17 (t, J = 6.7 Hz, 2H), 3.64 (q, J = 6.9 Hz, 1H), 2.37-2.22 (m, 2H), 1.63-1.56 (m, 2H), 1.48-1.40 (m, 2H), 1.32-1.25 (m, 5H), 1.22 (s, 9H), 1.18-1.10 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 165.8, 150.0, 139.3, 137.5, 130.9, 128.9, 128.7, 127.5, 125.8, 65.2, 52.5, 40.8, 34.5, 31.3, 28.7, 28.5, 25.8, 23.7, 17.4.

[0484] Example 57: Preparation of compound 55

[0485]

[0486] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 126 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 55 as a colorless oily liquid, with a yield of 95%, an enantiomeric excess of 91% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection:

[0487] 1 H NMR (600 MHz, Chloroform-d) δ 7.70-7.66 (m, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.51 (d, J = 1.0 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.30 (t, J = 7.5 Hz, 1H), 7.13 (d, J = 8.3 Hz, 2H), 4.32 (t, J = 6.7 Hz, 2H), 3.72 (q, J = 7.0 Hz, 1H), 2.42-2.33 (m, 2H), 1.75-1.70 (m, 2H), 1.56-1.48 (m, 2H), 1.37 (d, J = 6.9 Hz, 3H), 1.36-1.32 (m, 2H), 1.30 (s, 9H), 1.23 (q, J = 7.4 Hz, 2H). 13 C NMR (151 MHz, Chloroform-d) δ 211.2, 159.8, 155.8, 150.1, 145.8, 137.6, 127.7, 127.6, 127.1, 125.9, 123.9, 122.9, 113.9, 112.5, 65.5, 52.6, 40.9, 34.5, 31.4, 28.7, 28.6, 25.7, 23.8, 17.5.

[0488] Example 58: Preparation of compound 56

[0489]

[0490] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 79 (0.10 mmol), compound 127 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 56 as a colorless oily liquid with a yield of 68% and an enantiomeric excess of 93% determined by high performance liquid chromatography. The obtained compound 56 was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0491] 1 H NMR (400 MHz, Chloroform-d) δ 7.25 (t, J = 7.3 Hz, 2H), 7.17 (d, J = 7.4 Hz, 1H), 7.15-7.08 (m, 4H), 6.86 (d, J = 8.7 Hz, 2H), 3.79 (s, 3H), 3.68 (q, J = 7.0 Hz, 1H), 2.52 (t, J = 7.2 Hz, 2H), 2.42-2.29 (m, 2H), 1.57-1.45 (m, 4H), 1.36 (d, J = 7.0 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) δ 211.2, 158.8, 142.4, 132.8, 129.0, 128.5, 128.4, 125.8, 114.4, 55.4, 52.2, 40.7, 35.7, 30.9, 23.6, 17.6.

[0492] Example 59: Preparation of compound 57-R

[0493]

[0494] Ni(OAc)2-4H2O (0.01 mmol), (R)-ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 79 (0.10 mmol), compound 127 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHC03(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then purified by column chromatography to give compound 57-R as a colourless oil, in a yield of 65%, with an enantiomeric excess of -94% as determined by high performance liquid chromatography. The compound 57-R was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0495] 1 H NMR (400 MHz, Chloroform-d) δ 7.16 (t, J = 7.3 Hz, 2H), 7.07 (d, J = 7.3 Hz, 1H), 7.05-6.99 (m, 4H), 6.77 (d, J = 8.7 Hz, 2H), 3.69 (s, 3H), 3.59 (q, J = 7.0 Hz, 1H), 2.43 (t, J = 7.3 Hz, 2H), 2.33-2.22 (m, 2H), 1.49-1.34 (m, 4H), 1.26 (d, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 158.8, 142.3, 132.8, 129.0, 128.4, 128.3, 125.8, 114.4, 55.3, 52.2, 40.7, 35.7, 30.9, 23.6, 17.6.

[0496] Example 60: Preparation of compound 58

[0497]

[0498] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 98 (0.10 mmol), compound 128 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 58 as a colourless oily liquid, with a yield of 73% and an enantiomeric excess of 92% as determined by high performance liquid chromatography. The compound 58 obtained was subjected to nuclear magnetic resonance spectroscopy and the results were as follows:

[0499] 1 H NMR (400 MHz, Chloroform-d) δ 7.11 (d, J = 8.7 Hz, 2H), 6.83 (d, J = 8.7 Hz, 2H), 3.78 (s, 3H), 3.61 (t, J = 7.4 Hz, 1H), 2.40-2.31 (m, 1H), 2.03-1.93 (m, 1H), 1.87-1.80 (m, 1H), 1.78-1.71 (m, 1H), 1.69-1.65 (m, 1H), 1.64-1.58 (m, 2H), 1.48-1.41 (m, 1H), 1.38-1.29 (m, 1H), 1.25-1.18 (m, 2H), 1.17-1.04 (m, 2H), 0.79 (t, J = 7.4 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 214.0, 158.7, 131.2, 129.5, 114.2, 58.2, 55.3, 50.2, 29.2, 28.3, 26.1, 26.0, 25.9, 25.4, 12.4.

[0500] Example 61 : Preparation of compound 59

[0501]

[0502] Under a nitrogen atmosphere, Ni(OAc)₂·4H₂O (0.01 mmol), ligand L15 (0.012 mmol), and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min. Then, compound 98 (0.10 mmol), compound 129 (0.4 mmol), propyl chloroformate (i.e., compound 71) (0.20 mmol), and NaHCO₃ (0.30 mmol) were added sequentially. The resulting mixture was stirred for another 5 min, followed by the dropwise addition of trimethoxysilane (0.40 mmol). The reaction mixture was then removed from the nitrogen atmosphere and stirred at -10 °C for 48 hours. After the reaction was complete, the mixture was diluted with 5 mL of water and 5 mL of ethyl acetate. After the reaction mixture separated into layers, the aqueous phase was extracted twice with ethyl acetate (5 mL × 2). The organic phases were then combined and washed with saturated sodium chloride aqueous solution, dried with anhydrous sodium sulfate, and purified by column chromatography to obtain a colorless oily liquid compound 59 in 71% yield. The enantiomeric excess was determined to be 93% by high performance liquid chromatography. Compound 59 was subjected to 1H and 1C spectroscopy, and the results are as follows:

[0503] 1 H NMR (600MHz, Chloroform-d) δ7.12(d,J=8.5Hz,2H),6.84(d,J=8.6Hz,2H),3.79(s,3H),3.57(t,J=7.4Hz,1H),2.63-2.56(m, 1H),2.03-1.95(m,1H),1.76-1.64(m,3H),1.59-1.49(m,6H),1.48-1.38(m,5H),1.26-1.21(m,1H),0.81(t,J=7.4Hz,3H). 13 C NMR (151MHz,Chloroform-d)δ214.2,158.7,131.4,129.5,114.2,58.8,55.3,49.6,28.4,28.1,26.9,26.6,26.5,26.1,25.9,25.3,12.4.

[0504] Example 62: Preparation of Compound 60

[0505]

[0506] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 98 (0.10 mmol), compound 130 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 60 as a colorless oily liquid, with a yield of 84%, cis:trans = 1:1, and an enantiomeric excess of 92% / 92% determined by high performance liquid chromatography. The obtained compound 60 was detected by nuclear magnetic resonance and carbon spectrum, and the results were as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.11 (t, J = 9.7 Hz, 2H), 6.85 (d, J = 8.7 Hz, 2H), 3.78 (s, 3H), 3.48-3.39 (m, 1H), 2.49-2.13 (m, 3H), 2.06-1.96 (m, 1H), 1.67-1.56 (m, 2H), 1.54-1.37 (m, 2H), 1.36-1.24 (m, 2H), 1.00-0.88 (m, 2H), 0.87-0.81 (m, 4H), 0.78 (d, J = 20.4 Hz, 9H), 0.70-0.60 (m, 1H). 13 C NMR (151 MHz, Chloroform-d) δ 210.67, 158.8, 131.0, 129.46, 114.2, 60.5, 55.3, 48.2, 43.3, 33.8, 32.5, 31.0, 28.3, 27.5, 27.1, 25.1, 21.5, 12.2.

[0507] Example 63: Preparation of compound 61

[0508]

[0509] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 98 (0.10 mmol), compound 131 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere, stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 61 as a colorless oily liquid with a yield of 79%, dr = 2.3:1, and an enantiomeric excess of 91% / 89% determined by high performance liquid chromatography. The obtained compound 61 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows: 1 H NMR (600 MHz, Chloroform-d) δ 7.04 (d, J = 8.6 Hz, 2H), 6.78 (d, J = 8.6 Hz, 2H), 3.72 (s, 3H), 3.39 (t, J = 7.5 Hz, 1H), 2.27 (dt, J = 16.3, 4.6 Hz, 1H), 2.09-2.00 (m, 1H), 1.98-1.90 (m, 1H), 1.85-1.78 (m, 1H), 1.60-1.55 (m, 1H), 1.42-1.33 (m, 1H), 0.76-0.66 (m, 9H), 0.56 (dd, J = 9.8, 6.8 Hz, 3H). 13 C NMR (151 MHz, Chloroform-d) δ 210.9, 158.8, 131.1, 129.5, 114.3, 60.1, 55.3, 46.6, 34.4, 32.3,

[0510] Example 64: Preparation of compound 62

[0511]

[0512] Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 132 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, then column chromatography was used to separate and purify to give compound 62 as a colourless oil, with a yield of 72% and an enantiomeric excess of 94% as determined by high performance liquid chromatography. The compound 62 obtained was subjected to nuclear magnetic resonance spectroscopy and carbon spectrum detection, and the results were as follows:

[0513] 1 H NMR (600 MHz, Chloroform-d) δ 8.13 (d, J = 8.3 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 3.79 (q, J = 6.9 Hz, 1H), 2.54 (t, J = 6.8 Hz, 2H), 2.31 (t, J = 7.4 Hz, 2H), 2.04 (s, 3H), 1.98 (s, 3H), 1.93 (s, 3H), 1.75 (q, J = 7.0 Hz, 1H), 1.69 (d, J = 9.8 Hz, 1H), 1.50 (d, J = 10.2 Hz, 2H), 1.47-1.41 (m, 3H), 1.36 (d, J = 7.0 Hz, 3H), 1.34-1.28 (m, 3H), 1.24-1.17 (m, 11H), 1.15-1.09 (m, 9H), 1.09-1.04 (m, 3H), 0.99 (dt, J = 12.6, 7.3 Hz, 4H), 0.81-0.77 (m, 15H).

[0514] 13 C NMR(151 MHz, Chloroform-d) δ 210.3, 165.0, 149.6, 146.6, 140.7, 130.9, 128.7, 128.3, 127.0, 125.2, 123.3, 117.6, 75.2, 53.1, 41.6, 39.5, 37.6, 37.5, 37.4, 32.9, 31.9, 29.4, 29.2, 28.1, 24.9, 24.6, 23.9, 22.9, 22.8, 22.7, 21.2, 20.8, 19.9, 19.8, 17.7, 14.2, 13.2, 12.3, 12.0.

[0515] Example 65: Preparation of compound 63

[0516]

[0517] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 133 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 63 in the form of colorless oil with a yield of 60% and an enantiomeric excess of 91% determined by high performance liquid chromatography. The obtained compound 63 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows:

[0518] 1 H NMR(400 MHz, Chloroform-d) δ 7.75 (d, J = 8.8 Hz, 2H), 7.72 (d, J = 8.2 Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 5.08 (p, J = 6.3 Hz, 1H), 3.84 (q, J = 6.9 Hz, 1H), 2.37 (t, J = 7.4 Hz, 2H), 1.65 (s, 6H), 1.55-1.45 (m, 2H), 1.42 (d, J = 7.0 Hz, 3H), 1.25 (dd, J = 5.1, 2.2 Hz, 2H), 1.20 (d, J = 6.3 Hz, 14H), 0.85 (t, J = 6.9 Hz, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 210.3, 195.0, 173.2, 159.6, 145.0, 137.0, 132.0, 130.5, 130.4, 127.8, 117.2, 69.3, 52.9, 41.4, 31.8, 29.3, 29.1, 29.1, 25.4, 25.4, 23.8, 22.6, 21.5, 17.5, 14.1.

[0519] Example 66: Preparation of compound 64

[0520]

[0521] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L14 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 134 (0.10 mmol), compound 72 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere and stirred at 0 °C for 48 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 64 in the form of colorless oil with a yield of 86%, and the enantiomeric excess was 88% determined by high performance liquid chromatography. The obtained compound 64 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows:

[0522] 1 H NMR(400 MHz, Chloroform-d) δ 7.24 (d, J = 8.1 Hz, 1H), 6.99 (d, J = 7.6 Hz, 1H), 6.92 (s, 1H), 3.69 (q, J = 6.9 Hz, 1H), 2.92-2.85 (m, 2H), 2.50 (dd, J = 18.7, 8.6 Hz, 1H), 2.44-2.38 (m, 1H), 2.35 (td, J = 7.4, 2.9 Hz, 2H), 2.31-2.24 (m, 1H), 2.19-2.10 (m, 1H), 2.09-2.00 (m, 2H), 1.98-1.93 (m, 1H), 1.68-1.41 (m, 9H), 1.35 (d, J = 6.9 Hz, 3H), 1.28-1.23 (m, 2H), 1.22-1.13 (m, 8H), 0.90 (s, 3H), 0.85 (t, J = 7.0 Hz, 3H).

[0523] 13 C NMR (101 MHz, Chloroform-d) δ 211.4, 138.6, 138.2, 137.0, 128.2, 125.8, 125.5, 52.4, 50.5, 48.0, 44.3, 41.1, 38.1, 35.9, 31.8, 31.6, 29.4, 29.3, 29.1, 29.1, 26.5, 25.7, 23.9, 22.7, 21.6, 17.5, 14.1, 13.9.

[0524] Example 67: Synthesis of Compound A

[0525]

[0526] General preparation method: 4-dimethylaminopyridine (0.24 g, 2.0 mmol), 5-hexen-1-ol (1.00 g, 10.0 mmol, 1.0 equivalent), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (3.83 g, 20.0 mmol, 2.0 equivalent) and the corresponding acid (12.0 mmol, 1.2 equivalent, the R group of the acid corresponds to the R group of Compound A, respectively) were added into dichloromethane (30.0 mL) at 0 °C, and the reaction mixture was stirred at 25 °C for 24 h. After the reaction was completed, it was diluted with 40 mL of water and 20 mL of dichloromethane. After the reaction liquid was layered, the aqueous phase was extracted twice with dichloromethane (20 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain pure Compound A.

[0527] Different compounds A (Compound 135 - Compound 139) were prepared by the above general preparation method and using different corresponding acids RCOOH, respectively. The structures and characterization of the compounds 135 - Compound 139 are as follows:

[0528] hex-5-en-1-yl(1S,4R)-4,7,7-trimethyl-3-oxo-2-oxabicyclo[2.2.1]heptane-1-carboxylate(135)

[0529]

[0530] 1 H NMR (400 MHz, CDCI3) δ 5.77 (ddt, J = 16.9, 10.3, 6.7 Hz, 1 H), 5.09 - 4.87 (m, 2 H), 4.30 - 4.18 (m, 2 H), 2.41 (ddd, J = 13.3, 10.7, 4.4 Hz, 1 H), 2.10 - 1.97 (m, 3 H), 1.91 (ddd, J = 13.3, 10.7, 4.4 Hz, 1 H), 1.74 - 1.63 (m, 3 H), 1.52 - 1.42 (m, 2 H), 1.1 1 (s, 3 H), 1.05 (s, 3 H), 0.95 (s, 3 H). 13 C NMR (101 MHz, Chloroform-d) δ 178.3, 167.7, 138.2, 1 15.2, 91.3, 65.6, 54.9, 54.2, 33.3, 30.8, 29.1, 28.1, 25.2, 16.9, 16.9, 9.8.

[0531] hex-5-en-1-yl 2-(11-oxo-6,11-dihydrodibenzo[b,e]oxepin-2-yl)acetate(136)

[0532]

[0533] 1 H NMR(400 MHz, CDCI3) δ 8.12 (d, J = 2.4 Hz, 1 H), 7.89 (dd, J = 7.5, 1.4 Hz, 1 H), 7.59-7.52 (m, 1 H), 7.51 -7.40 (m, 2H), 7.36 (dd, J = 7.5, 1.4 Hz, 1 H), 7.02 (d, J = 8.4 Hz, 1 H), 5.77 (ddt, J = 16.9, 10.2, 6.7 Hz, 1 H), 5.18 (s, 2H), 5.04-4.91 (m, 2H), 4.10 (t, J = 6.6 Hz, 2H), 3.63 (s, 2H), 2.10-2.01 (m, 2H), 1.69-1.60 (m, 2H), 1.48-1.36 (m, 2H). 13 C NMR (101 MHz, CDCI3) δ 191.0, 171.6, 160.6, 140.6, 138.4, 136.5, 135.7, 132.9, 132.6, 129.6, 129.4, 128.1, 127.9, 125.2, 121.1, 114.9, 73.7, 65.0, 40.4, 33.3, 28.1, 25.2.

[0534] hex-5-en-1 -yl (S)-2-(6-methoxynaphthalen-2-yl)propanoate (137)

[0535]

[0536] 1 H NMR (400 MHz, Chloroform-d) δ 7.74-7.65 (m, 3H), 7.41 (dd, J = 8.4, 1.9 Hz, 1 H), 7.17-7.09 (m, 2H), 5.70 (ddt, J = 17.0, 10.2, 6.7 Hz, 1 H), 4.98-4.87 (m, 2H), 4.08 (t, J = 6.6 Hz, 2H), 3.91 (s, 3H), 3.85 (q, J = 7.1 Hz, 1 H), 2.02-1.95 (m, 2H), 1.60-1.53 (m, 5H), 1.35 (p, J = 7.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 174.9, 157.7, 138.4, 135.9, 133.8, 129.4, 129.1, 127.2, 126.4, 126.0, 119.1, 114.8, 105.7, 64.8, 55.4, 45.7, 33.3, 28.1, 25.2, 18.6.

[0537] hex-5-en-1-yl 3-(4,5-diphenyloxazol-2-yl)propanoate (138)

[0538]

[0539] 1 H NMR (400 MHz, Chloroform-d) δ 7.63 (d, J = 8.3 Hz, 2H), 7.58 (d, J = 8.2 Hz, 2H), 7.39 - 7.29 (m, 6H), 5.77 (ddt, J = 16.9, 10.1, 6.7 Hz, 1H), 5.05 - 4.91 (m, 2H), 4.13 (t, J = 6.6 Hz, 2H), 3.19 (t, J = 7.5 Hz, 2H), 2.92 (t, J = 7.5 Hz, 2H), 2.06 (q, J = 7.2 Hz, 2H), 1.69 - 1.61 (m, 2H), 1.44 (p, J = 7.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 172.2, 161.9, 145.5, 138.4, 135.2, 132.6, 129.1, 128.75, 128.66, 128.6, 128.2, 128.0, 126.6, 115.0, 64.9, 33.4, 31.3, 28.1, 25.3, 23.7.

[0540] hex-5-en-1-yl 2-(1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl)acetate (139)

[0541]

[0542] 1 H NMR (400 MHz, Chloroform-d) δ 7.68 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 6.99 (d, J = 2.6 Hz, 1H), 6.89 (d, J = 9.0 Hz, 1H), 6.69 (dd, J = 9.0, 2.6 Hz, 1H), 5.76 (ddt, J = 16.9, 10.2, 6.6 Hz, 1H), 5.05 - 4.90 (m, 2H), 4.13 (t, J = 6.6 Hz, 2H), 3.85 (s, 3H), 3.68 (s, 2H), 2.41 (s, 3H), 2.07 (t, J = 7.1 Hz, 2H), 1.65 (dd, J = 15.2, 6.7 Hz, 2H), 1.42 (p, J = 7.6 Hz, 2H). 13 C NMR(101 MHz, Chloroform-d) δ 171.1, 168.4, 156.1, 139.3, 138.3, 136.0, 134.0, 131.3, 130.9, 130.8, 129.2, 115.1, 115.0, 112.8, 111.8, 101.4, 65.1, 55.8, 33.3, 30.5, 28.1, 25.2, 13.5.

[0543] Example 68: Preparation of compound 65

[0544]

[0545] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 135 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 65 as a colorless oily liquid with a yield of 79% and an enantiomeric excess of 92% determined by high performance liquid chromatography. The obtained compound 65 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows:

[0546] 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (d, J = 8.4 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 4.15 (t, J = 6.7 Hz, 2H), 3.71 (q, J = 7.0 Hz, 1H), 2.43-2.31 (m, 3H), 2.04-1.97 (m, 1H), 1.94-1.87 (m, 1H), 1.71-1.65 (m, 1H),

[0547] 1.60 (dd, J = 8.2, 6.6 Hz, 2H), 1.51-1.44 (m, 2H), 1.35 (d, J = 7.0 Hz, 3H), 1.29 (s, 9H), 1.27-1.22 (m, 2H),

[0548] 1.21-1.14 (m, 2H), 1.10 (s, 3H), 1.03 (s, 3H), 0.93 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 178.2, 167.5, 150.0, 137.5, 127.5, 125.8, 91.2, 65.6, 54.8, 54.1, 52.5, 40.8, 34.4, 31.4, 30.6, 29.0, 28.5, 28.3, 25.6, 23.6, 17.4, 16.8, 16.8, 9.7.

[0549] Example 69: Preparation of compound 66

[0550]

[0551] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 136 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and then column chromatography was used for separation and purification to obtain compound 66 in the form of colorless oil with a yield of 89% and an enantiomeric excess of 94% determined by high performance liquid chromatography. The obtained compound 66 was subjected to nuclear magnetic resonance and carbon spectrum detection, and the results were as follows:

[0552] 1 H NMR(400 MHz, Chloroform-d) δ 8.11 (d, J = 2.4 Hz, 1H), 7.88 (d, J = 7.5 Hz, 1H), 7.55 (t, J = 7.7 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.41 (dd, J = 8.5, 2.4 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 1H), 5.17 (s, 2H), 4.03 (t, J = 6.7 Hz, 2H), 3.71 (q, J = 7.0 Hz, 1H), 3.61 (s, 2H), 2.40 - 2.27 (m, 2H), 1.58 - 1.51 (m, 2H), 1.50 - 1.41 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.25 - 1.10 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 190.9, 171.6, 160.5, 150.0, 140.5, 137.6, 136.4, 135.7, 132.9, 132.5, 129.6, 129.3, 128.0, 127.9, 127.6, 125.8, 125.2, 121.1, 73.7, 65.1, 52.5, 40.9, 40.4, 34.5, 31.4, 28.7, 28.4, 25.7, 23.7, 17.5.

[0553] Example 70: Preparation of compound 67

[0554]

[0555] Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.10 mmol), compound 137 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 67 as a colorless oily liquid, with a yield of 96%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 67:

[0556] 1 H NMR (400 MHz, Chloroform-d) δ 7.70 (d, J = 8.9 Hz, 2H), 7.66 (s, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.33 (d, J = 8.3 Hz, 2H), 7.18-7.08 (m, 4H), 4.02 (t, J = 6.6 Hz, 2H), 3.91 (s, 3H), 3.83 (q, J = 7.1 Hz, 1H), 3.68 (q, J = 7.0 Hz, 1H), 2.35-2.17 (m, 2H), 1.57 (d, J = 7.1 Hz, 3H), 1.53-1.43 (m, 2H), 1.42-1.33 (m, 5H), 1.30 (d, J = 0.8 Hz, 9H), 1.18-1.03 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 174.8, 157.7, 150.0, 137.6, 135.9, 133.7, 129.4, 129.0, 127.6, 127.2, 126.3, 126.0, 125.8, 119.0, 105.6, 64.8, 55.4, 52.5, 45.6, 40.8, 34.5, 31.4, 28.6, 28.4, 25.6, 23.7, 18.6, 17.5.

[0557] Example 71: Preparation of compound 68

[0558]

[0559] Ni(OAc)2-4H2O (0.005 mmol), ligand L15 (0.006 mmol) and 2-methyltetrahydrofuran (0.1 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.05 mmol), compound 138 (0.2 mmol), propyl chloroformate (i.e. compound 71) (0.10 mmol) and NaHCO3(0.15 mmol) were added in turn. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.20 mmol) was added dropwise. The reaction was taken out of the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound 68 as a colorless oily liquid, with a yield of 85%, an enantiomeric excess of 92% determined by high performance liquid chromatography, and the following results were obtained by hydrogen spectrum and carbon spectrum detection of the obtained compound 68:

[0560] 1 H NMR (400 MHz, Chloroform-d) δ 7.54 (d, J = 8.0 Hz, 2H), 7.48 (d, J = 7.9 Hz, 2H), 7.32 - 7.19 (m, 8H), 7.04 (d, J = 8.4 Hz, 2H), 3.98 (t, J = 6.7 Hz, 2H), 3.63 (q, J = 6.9 Hz, 1H), 3.09 (dd, J = 8.2, 6.8 Hz, 2H), 2.81 (t, J = 7.5 Hz, 2H), 2.30 - 2.17 (m, 2H), 1.51 - 1.45 (m, 2H), 1.41 - 1.34 (m, 2H), 1.28 (d, J = 7.0 Hz, 3H), 1.22 (s, 9H), 1.19 - 1.12 (m, 2H), 1.11 - 1.01 (m, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 211.2, 172.1, 161.9, 150.1, 145.5, 137.6, 135.2, 132.5, 129.1, 128.7, 128.6, 128.6, 128.2, 128.0, 127.6, 126.6, 125.9, 64.9, 52.6, 40.9, 34.5, 31.4, 31.3, 28.7, 28.5, 25.7, 23.7, 23.7, 17.5.

[0561] Example 72: Preparation of compound 69

[0562]

[0563] Ni(OAc)2-4H2O (0.005 mmol), ligand L15 (0.006 mmol) and 2-methyltetrahydrofuran (0.1 mL) were mixed under a nitrogen atmosphere, stirred at 25 °C for 10 min, then compound 70 (0.05 mmol), compound 139 (0.2 mmol), propyl chloroformate (i.e. compound 71) (0.10 mmol) and NaHCO3(0.15 mmol) were added sequentially. The resulting mixture was stirred for a further 5 min, then trimethoxysilane (0.20 mmol) was added dropwise. The reaction was removed from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was complete, 5 mL water and 5 mL ethyl acetate were added. After the reaction was partitioned, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). The organic phases were then combined and washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and purified by column chromatography to give compound 68 as a colourless oil in 87% yield with an enantiomeric excess of 92% as determined by high performance liquid chromatography. Compound 68 was characterised by1H and13C NMR spectroscopy as follows:

[0564] 1 H NMR (400 MHz, Chloroform-d) δ 7.65 (d, J = 8.5 Hz, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.3 Hz, 2H), 7.12 (d, J = 8.3 Hz, 2H), 6.95 (d, J = 2.6 Hz, 1H), 6.86 (d, J = 9.0 Hz, 1H), 6.65 (dd, J = 9.0, 2.5 Hz, 1H), 4.04 (t, J = 6.7 Hz, 2H), 3.82 (s, 3H), 3.71 (q, J = 6.9 Hz, 1H), 3.64 (s, 2H), 2.37 (s, 3H), 2.36-2.25 (m, 2H), 1.57-

[0565] 1.50 (m, 2H), 1.47-1.40 (m, 2H), 1.36 (d, J = 7.0 Hz, 3H), 1.30 (s, 9H), 1.23-1.09 (m, 4H). 13 C NMR (101 MHz, Chloroform-d) δ 211.1, 170.9, 168.3, 156.0, 150.0, 139.3, 137.5, 135.9, 134.0, 131.2, 130.8, 130.7, 129.1, 127.5, 125.8, 114.9, 112.7, 111.6, 101.4, 65.0, 55.7, 52.5, 40.8, 34.4, 31.3, 30.4, 28.6, 28.4, 25.6, 23.6, 17.4, 13.4.

[0566] Example 73: Preparation of compound d-1-S

[0567]

[0568] Under a nitrogen atmosphere, Ni(OAc)2-4H2O (0.01 mmol), ligand L15 (0.012 mmol) and 2-methyltetrahydrofuran (0.2 mL) were mixed and stirred at 25 °C for 10 min, then compound a-1 (0.10 mmol), compound c-1 (0.4 mmol), propyl chloroformate (i.e. compound 71) (0.20 mmol) and NaHCO3(0.30 mmol) were added successively. The resulting mixture was stirred for another 5 min, then trimethoxysilane (0.40 mmol) was added dropwise. The reaction was taken out from the nitrogen atmosphere and stirred at -10 °C for 36 h. After the reaction was completed, 5 mL of water and 5 mL of ethyl acetate were added. After the reaction was layered, the aqueous phase was extracted twice with ethyl acetate (5 mL x 2). Then the organic phase was combined and washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate, and column chromatography was used for separation and purification to obtain compound d-1-S with a yield of 97% and an enantiomeric excess of 94% determined by high performance liquid chromatography. Mass of compound d-1-S: [M+H] + : 231.

[0569] Examples 74-83: Preparation of compounds d-2-S to d-11-S

[0570] Referring to the preparation method of Example 73, compound a-1 was adjusted to other substrates (see Table 8), and the rest of the operations were the same as those of Example 73 to prepare compounds d-2-S to d-11-S, respectively. The results are shown in Table 8.

[0571] Table 8: Preparation and results of compounds d-2-S to d-11-S

[0572]

[0573] The methods of the present application have been described by preferred examples, and the related personnel can obviously make changes or appropriate changes and combinations to the methods and applications described herein within the content, spirit and scope of the present application to realize and apply the present technology. Those skilled in the art can refer to the content herein to make appropriate improvements to the process parameters. It is particularly pointed out that all similar substitutions and changes are obvious to those skilled in the art, and they are considered to be included in the present application.

Claims

1. A method for synthesizing compound d, characterized in that, include: Compounds a, b, and c react in the presence of a catalyst, ligand, base, silane, and solvent in the presence of nitrogen or an inert gas atmosphere to give compound d. in, Ar is selected from: substituted or unsubstituted aryl groups, substituted or unsubstituted heteroaryl groups; R 1 Selected from: hydrogen, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 cycloalkyl; R 8 Selected from: n-propyl, methyl, ethyl, isopropyl, sec-butyl, phenyl, benzyl, n-butyl, n-pentyl, isobutyl, sec-butyl, cyclopentyl, n-hexyl, n-heptyl, n-decyl; R 2 R 3 R 4 The definition is selected from one of the following groups: (1)R 3 Selected from hydrogen, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 cycloalkyl; R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclic group; wherein, in compound c, the R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9, or 10-membered carbocyclic group containing only one alkenyl group and no alkynyl group; in compound d, the R 2 R 4 and R 2 R 4 The adjacent carbon atoms together form substituted or unsubstituted 4-membered, 5-membered, 6-membered, 7-membered, 8-membered, 9-membered or 10-membered carbon cycloalloys, which do not contain alkenyl or ynyl groups. (2)R 3 and R 4 It is hydrogen; R 2 C6-C, whether substituted or not 12 aryl, substituted or unsubstituted C3-C 12 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocyclic groups, substituted or unsubstituted 3- to 10-membered heterocyclic alkyl groups; (3)R 4 It is hydrogen; R 2 R 3 and R 2 R 3 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered cycloalkyl, a substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered bridged heterocycloalkyl, a substituted or unsubstituted C6-C20 aryl, or a substituted or unsubstituted C6-C20 heteroaryl. (4)R 4 It is hydrogen; R 2 and R 3 Each C6-C is independently selected from substituted or unsubstituted C6-C. 20 aryl, substituted or unsubstituted C4-C 20 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocyclic alkyl groups.

2. The synthesis method according to claim 1, wherein the ligand is an S-configuration ligand, and the compound d is... Alternatively, the ligand may be an R-configuration ligand; the compound d may be... and / or The catalyst is selected from nickel catalysts; and / or The catalyst is selected from NiI2, NiBr2, NiCl2, NiBr2·DME, NiCl2·6H2O, Ni(COD)2, Ni(acac)2, and Ni(OTf). 2、 At least one of Ni(OAc)2 and Ni(OAc)2·4H2O, preferably NiBr 2、 NiCl 2、 NiCl2·6H2O, Ni(COD) 2、 At least one of Ni(OAc)2 and Ni(OAc)2·4H2O, more preferably at least one of Ni(OAc)2 and Ni(OAc)2·4H2O; and / or Optionally, the structure of the ligand is as shown in compound S4. in, The chiral center indicated by "*" has an S configuration or an R configuration. The R configuration in compound S4 is... 5 R 6 R 7 The groups in the text are selected from any group ①-④: ①The R 5 Selected from H, C1-C 10 Straight-chain alkyl, C3-C 10 Branched alkyl groups; The R 6 Selected from substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; The R 7 Selected from substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; or ②The R 5 Selected from H, C1-C 10 Straight-chain alkyl; The R 6 Selected from tert-butyl, phenyl, and benzyl; The R 7 Selected from phenyl, Or, as described in ③, R 5 and R 7 It forms C6-C with adjacent carbons. 12 Aromatic rings; The R 6 Selected from substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; Or R as described in ④ 5 and R 7 It forms a phenyl group with adjacent carbon atoms; The R 6 It is phenyl; Optionally, the ligand is selected from at least one of ligands L3, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, and L21, preferably at least one of ligands L12, L13, L14, and L15, and more preferably at least one of ligands L14 and L15. Alternatively, the ligand is selected from at least one of ligand(R)-L3, ligand(R)-L8, ligand(R)-L9, ligand(R)-L10, ligand(R)-L11, ligand(R)-L12, ligand(R)-L13, ligand(R)-L14, ligand(R)-L15, ligand(R)-L16, ligand(R)-L17, ligand(R)-L18, ligand(R)-L19, ligand(R)-L20, and ligand(R)-L21, preferably at least one of ligand(R)-L12, ligand(R)-L13, ligand(R)-L14, and ligand(R)-L15, more preferably at least one of ligand(R)-L14 and ligand(R)-L15. and / The alkali is selected from at least one of Na₂CO₃, NaHCO₃, K₂CO₃, and Cs₂CO₃, preferably NaHCO₃; and / or The silane is selected from at least one of triethylsilane, diphenylsilane, triethoxysilane, trimethoxysilane, methyldimethoxysilane, and methyldiethoxysilane; The solvent is selected from at least one of 2-methyltetrahydrofuran, tetrahydrofuran, ethylene glycol dimethyl ether, 1,4-dioxane, and N,N-dimethylacetamide, preferably at least one of 2-methyltetrahydrofuran, tetrahydrofuran, ethylene glycol dimethyl ether, and 1,4-dioxane, and more preferably 2-methyltetrahydrofuran; The reaction temperature is -20℃ to 0℃, or -15℃ to -5℃; preferably -10℃.

3. The synthetic method according to any one of claims 1-2, wherein at least one hydrogen atom in Ar, which is substituted as an aryl or heteroaryl group, is independently selected from fluorine, chlorine, bromine, amino, nitro, C1-C6 straight-chain alkyl, C3-C6 branched alkyl, C6-C6 branched alkyl, etc. 20 Aryl, trifluoromethyl, cyano, trimethylsilyl, pivalamido, acetoxy, dimethylamino, methoxy, methylthio, acetyl, methoxycarbonyl, trifluoromethoxy, =O -COOCH3 replaced; and / or The substituted or unsubstituted aryl group in Ar is selected from substituted or unsubstituted phenyl, substituted or unsubstituted benzocyclobutenyl, or substituted or unsubstituted aryl groups. The substituted or unsubstituted heteroaryl group in Ar is selected from substituted or unsubstituted 1,3-benzodioxonyl or substituted or unsubstituted indolyl.

4. The synthesis method according to any one of claims 1-3, wherein R 1 The substitution in is that it is substituted by at least one benzyloxy group; and / or The R 1 Selected from H, unsubstituted C1-C 10 Straight-chain alkyl or C1-C substituted with at least one OBn group 10 Straight-chain alkyl groups; and / or The R 1 Selected from H, methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl or -CH2-OBn.

5. The synthesis method according to any one of claims 1-4, R 2 R 3 R 4 The definition is selected from one of the following groups: (i)R 3 Selected from hydrogen; R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4-, 5-, 6-, 7-, 8-, 9-, or 10-membered carbocyclic group; among which, In compound c, the R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9, or 10-membered carbocyclic group containing only one alkenyl group and no alkynyl group; in compound d, the R 2 R 4 and R 2 R 4 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered carbocyclic group, which contains neither alkenyl nor ynyl groups; (ii)R 3 and R 4 It is hydrogen; R 2 C6-C, whether substituted or not 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C3-C 10 Heterocyclic alkyl groups; The R 2 The substitution in is achieved by being replaced by at least one substituent selected from the following: tert-butoxycarbonyl, fluorine, chlorine, bromine, C6-C20 heteroaryl, C6-C20 aryl, C3-C 10 cycloalkyl, methoxycarbonyl, Benzyloxy, acetyloxy, tert-butyldimethylsiloxy, acetyl, hydroxyl ＝O、 Or the R 2 The substitution in is achieved by being replaced by at least one substituent selected from the following: tert-butoxycarbonyl, fluorine, chlorine, bromine, phenyl, C3-C 10 Cycloalkyl groups (e.g., C3 cycloalkyl, C4 cycloalkyl, C5 cycloalkyl, C6 cycloalkyl, C7 cycloalkyl, C8 cycloalkyl, C9 cycloalkyl, C...) 10 cycloalkyl), methoxycarbonyl, Benzyloxy, acetyloxy, tert-butyldimethylsiloxy, acetyl, hydroxyl ＝O、 (iii)R 4 It is hydrogen; R 2 R 3 and R 2 R 3 Each adjacent carbon atom together forms a substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered cycloalkyl, a substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered bridged heterocycloalkyl, a substituted or unsubstituted C6-C20 aryl, or a substituted or unsubstituted C6-C20 heteroaryl. The substitution in the substituted 4, 5, 6, 7, 8, 9 or 10-membered cycloalkyl, substituted or unsubstituted 4, 5, 6, 7, 8, 9 or 10-membered bridged heterocycloalkyl, substituted or unsubstituted C6-C20 aryl, substituted or unsubstituted C6-C20 heteroaryl is substituted by at least one substituent selected from the following: C1-C10 straight-chain alkyl, C3-C10 branched alkyl, methoxy, =O, phenyl, p-chlorobenzoyl; (iv)R 4 It is hydrogen; R 2 and R 3 Each C6-C is independently selected from substituted or unsubstituted C6-C. 12 aryl, substituted or unsubstituted C4-C 12 heteroaryl, substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C3-C 10 Heterocyclic alkyl groups; Or R 2 and R 3 Each of the following is independently selected from substituted or unsubstituted C1-C6 straight-chain alkyl, substituted or unsubstituted C3-C6 branched alkyl, substituted or unsubstituted C3-C6 cycloalkyl, and substituted or unsubstituted C3-C6 heterocyclic alkyl.

6. The synthesis method according to any one of claims 1-5, The compound a is selected from compounds 70, 73-103, 132-134, a-1, a-2, a-3, a-4, a-5, a-6, a-7, a-8, a-9, a-10, and a-11. Compound c is selected from compounds 72, 104-131, 135-139, and c-1. and / or The compound d is selected from compounds 1-56, 58-69, d-1, d-2, d-3, d-1-S, d-2-S, d-3-S, d-4, d-4-S, d-5, d-5-S, d-6, d-6-S, d-7, d-7-S, d-8, d-8-S, d-9, d-9-S, d-10, d-10-S, d-11, and d-11-S. Alternatively, compound d may be selected from compounds 1-R to 56-R, compounds 58-R to 69-R, compounds d-1-R, compounds d-2-R, compounds d-3-R, compounds d-4-R, compounds d-5-R, compounds d-6-R, compounds d-7-R, compounds d-8-R, compounds d-9-R, compounds d-10-R, and compounds d-11-R.

7. The synthesis method according to any one of claims 1-6, wherein the molar ratio of compound a to compound b is 1.0:1.0-1.0:5.0; preferably 1.0:2.0; and / or The molar ratio of compound a to compound c is 1.0:1.0-1.0:5.0; preferably 1.0:4.0; and / or The molar ratio of compound a to the catalyst is 1.00:0.01-1.00:0.20; preferably 1.00:0.10; and / or The molar ratio of compound a to the ligand is 1.00:0.01-1.00:0.30; preferably 1.00:0.12; and / or The molar ratio of compound a to alkali is 1.0:1.0-1.0:5.0; preferably 1.0:3.0; and / or The molar ratio of compound a to silane is 1.0:1.0-1.0:5.0; preferably 1.0:4.0; and / or 0.1 mol to 1.0 mol of compound a is added per 1 L of the solvent; preferably 0.5 mol of compound a is added per 1 L of the solvent.

8. The synthesis method according to any one of claims 1-7, wherein the synthesis method comprises: Compounds a, b, and c react in the presence of a catalyst, ligand, base, silane, and solvent under a nitrogen or inert gas atmosphere to give compound d. or The synthesis method includes: mixing compounds a, b, and c with a catalyst, ligand, base, silane, and solvent under a nitrogen or inert gas atmosphere to obtain a mixture; then removing the mixture from the nitrogen or inert gas atmosphere and reacting it to obtain compound d; or The synthesis method includes: mixing a catalyst and ligand with a solvent under a nitrogen or inert gas atmosphere, then sequentially adding compound a, compound c, compound b, a base, and silane, mixing, and reacting to obtain compound d; or The synthesis method includes: mixing a catalyst and ligand with a solvent under a nitrogen or inert gas atmosphere, then sequentially adding compound a, compound c, compound b, a base and silane, mixing to obtain a mixture, then removing the mixture from the nitrogen or inert gas atmosphere and reacting to obtain compound d.

9. The synthesis method according to any one of claims 1-8, wherein the synthesis method further comprises performing post-processing after the reaction is completed; Optionally, the post-processing includes: Water and ethyl acetate were added, and the mixture was allowed to separate into an aqueous phase and an organic phase. The aqueous phase was extracted with ethyl acetate, and the organic phases were combined. The combined organic phases were washed with a saturated sodium chloride aqueous solution to remove residual water, and then separated and purified.

10. A compound selected from: compounds 4-9, compounds 13-25, compounds 27, compounds 29, compounds 31-56, compounds 58-69, compounds 4-R-9-R, compounds 13-R-25-R, compounds 27-R, compounds 29-R, compounds 31-R to 56-R, compounds 58-R to 69-R, ligand L10-L21, ligand(R)-L10-ligand(R)-L21, 11. A method for preparing a ligand compound, characterized in that, The structure of the ligand compound is shown in compound S4, and the preparation method includes: Step 3: Preparation of compound S4: Compound S3 reacts with sodium methoxide in solvent 1. After a first post-treatment, crude product C is obtained. Crude product C reacts with compound S5 in solvent 2 in the presence of a catalyst. After a second post-treatment, compound S4 is obtained. The configuration of the chiral center marked with "*" in compound S5 is the same as that of the chiral center marked with "*" in compound S4. Optionally, the catalyst in step 3 includes at least one of p-toluenesulfonic acid and hydrochloric acid; Optionally, the solvent 1 includes at least one of methanol and ethanol; Optionally, the solvent 2 comprises at least one of toluene, ethylene glycol dimethyl ether, and 1,4-dioxane; Optionally, the reaction temperature for preparing crude product C in step 3 is 15℃-45℃; Optionally, the reaction temperature of the crude product C and compound S5 in step 3 is 70℃-110℃; Optionally, the molar ratio of compound S3 to sodium methoxide is 1.0:0.1 to 1.0:1.0; Optionally, 0.1 mol to 0.5 mol of compound S3 is added to each 1 L of solvent 1; Optionally, the molar ratio of the crude product C to compound S5 is 1.0:1.0-1.0:1.5; Optionally, 0.2 mol to 1.0 mol of the crude product C is added to each 1 L of solvent 2; Optionally, the molar ratio of the catalyst to the crude product C is 0.5:10.0-2.0:10.0 or 1.0:10.0; Optionally, the first post-processing includes: removing solvent 1, extracting with ethyl acetate and water, separating the liquid, drying the ethyl acetate phase, filtering, and concentrating the filtrate; Optionally, the second post-treatment includes: quenching the reaction with water, extracting with ethyl acetate, separating the liquid, drying the ethyl acetate phase, filtering, concentrating the filtrate, and purifying. Optionally, the R 5 R 6 R 7 The groups in the text are selected from any group ①-④: ①The R 5 Selected from H, C1-C 10 Straight-chain alkyl, C3-C 10 Branched alkyl groups; The R 6 Selected from substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; The R 7 Selected from substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; or ②The R 5 Selected from H, C1-C 10 Straight-chain alkyl; The R 6 Selected from tert-butyl, phenyl, and benzyl; The R 7 Selected from phenyl, Or, as described in ③, R 5 and R 7 It forms C6-C with adjacent carbons. 12 Aromatic rings; The R 6 Selected from substituted or unsubstituted C1-C 10 Straight-chain alkyl, substituted or unsubstituted C3-C 10 Branched alkyl, substituted or unsubstituted C6-C 12 aryl, substituted or unsubstituted C4-C 12 Mixed aromatics; Or R as described in ④ 5 and R 7 It forms a phenyl group with adjacent carbon atoms; The R 6 It is phenyl; Optionally, the compound S4 is selected from the following structures: Optionally, the method for preparing the ligand compound further includes a step for preparing compound S3: Step 2: Preparation of compound S3: Compound S2 reacts with an oxidant in solvent 3 to give crude product A. Crude product A reacts with trimethylcyanosilane and dimethylcarbamoyl chloride in solvent 4. After a third post-treatment, compound S3 is obtained. Optionally, the oxidant includes at least one of m-chloroperoxybenzoic acid, hydrogen peroxide, peracetic acid, and urea peroxide; Optionally, the reaction temperature for obtaining crude product A in step 2 is 15℃-35℃; Optionally, the reaction temperature for obtaining compound S3 in step 2 is 15°C-35°C; Optionally, the molar ratio of compound S2 to m-chloroperoxybenzoic acid is 1.0:1.0-1.0:2.0; Optionally, 1-5 L of solvent 3 is added for every 1 mol of the compound S2; Optionally, the solvent 4 includes at least one of dichloromethane, trichloromethane, and ethyl acetate; Optionally, the molar ratio of the crude product A to trimethylcyanosilane is 0.5:1.0-2.0:1.0; Optionally, the molar ratio of the crude product A to dimethylcarbamoyl chloride is 0.5:1.0-2.0:1.0; Optionally, 1-5 L of solvent 4 is added for every 1 mol of the crude product A; Optionally, the third post-processing includes: mixing with 10 wt% potassium carbonate aqueous solution, extracting with dichloromethane, separating the liquid, washing the dichloromethane phase with saturated sodium chloride aqueous solution, drying the washed dichloromethane phase, filtering, concentrating the filtrate, and purifying.

12. The method for preparing the ligand compound according to claim 11 further includes a step of preparing compound S2: Step 1: Preparation of compound S2: Compound S1 and arylboronic acid R 7 B(OH)2 reacts in solvent 5 in the presence of a base and a catalyst, and under the protection of a nitrogen or inert gas atmosphere. After a fourth post-treatment, compound S2 is obtained. Where R 5 and R 7 The group in the compound is selected from any one of the groups ①-② in claim 11, or the compound S4 is selected from the structures L3, L4, L5, L8, L9, L10, L11, L12, L13, L14, L15, L16, L17, L18, L19, L20, L21, (R)-L3, (R)-L4, (R)-L5, (R)-L8, (R)-L9, (R)-L10, (R)-L11, (R)-L12, (R)-L13, (R)-L14, (R)-L15, (R)-L16, (R)-L17, (R)-L18, (R)-L19, (R)-L20, (R)-L21; Optionally, the alkali includes at least one of sodium carbonate, potassium carbonate, cesium carbonate, sodium hydroxide, and potassium phosphate; Optionally, the catalyst comprises at least one of tetra(triphenylphosphine)palladium, palladium acetate, di(triphenylphosphine)palladium chloride, and palladium chloride; Optionally, the solvent 5 is toluene, ethanol, and water; Optionally, the reaction temperature in step 1 is 80℃-100℃; Optionally, the compound S1 is reacted with arylboronic acid R 7 The molar ratio of B(OH)2 to feed is 1:1-1:5; Optionally, the molar ratio of compound S1 to alkali is 1:5 to 1:10; Optionally, the molar ratio of compound S1 to catalyst is 1.00:0.01-1.00:0.10; Optionally, each 1 mol of the compound S1 corresponds to 5 L-10 L of the solvent 5; Optionally, the volume ratio of toluene, ethanol and water in solvent 5 is (30.0-40.0):(5.0-10.0):(30.0-40.0) or 35.0:7.5:35.0; Optionally, the fourth post-processing includes: Add an aqueous solution of ammonium chloride, then extract with ethyl acetate, combine the ethyl acetate phases and dry them, then concentrate and purify.

13. A method for preparing ligand L6, characterized in that, Includes the following steps: Compound S3 reacts with sodium methoxide in solvent 6, followed by a fifth post-treatment to give crude product C. Crude product C reacts with (1S,2R)-(-)- Cis-1-amino-2-indanol was reacted in solvent 7 in the presence of a catalyst, and after a sixth post-treatment, ligand L6 was obtained; That In compound S3, R 5 For H, R 7 It is phenyl; Optionally, the catalyst in the preparation method of the ligand L6 includes at least one of p-toluenesulfonic acid and hydrochloric acid; Optionally, the solvent 6 includes at least one of anhydrous methanol and ethanol; Optionally, the solvent 7 comprises at least one of toluene, ethylene glycol dimethyl ether, and 1,4-dioxane; Optionally, the reaction temperature for preparing crude product C in the method for preparing ligand L6 is 15℃-45℃; Optionally, in the method for preparing the ligand L6, the reaction temperature of the crude product C with (1S,2R)-(-)-cis-1-amino-2-indanol is 70℃-110℃; Optionally, the molar ratio of compound S3 to sodium methoxide is 1.0:0.1 to 1.0:1.0; Optionally, 0.1 mol to 0.5 mol of compound S3 is added to each 1 L of solvent 6; Optionally, the molar ratio of the crude product C to (1S,2R)-(-)-cis-1-amino-2-indanol is 1.0:1.0-1.0:1.5; Optionally, 0.2 mol to 1.0 mol of the crude product C is added to each 1 L of the solvent 7; Optionally, the molar ratio of the catalyst to the crude product C is 0.5:10-2:10 or 1:10; Optionally, the fifth post-processing includes: removing solvent 6, extracting with ethyl acetate and water, separating the liquid, drying the ethyl acetate phase, filtering, and concentrating the filtrate; Optionally, the sixth post-processing includes: quenching the reaction with water, extracting with ethyl acetate, separating the liquid, drying the ethyl acetate phase, filtering, concentrating the filtrate, and purifying.

Images