CN112300214A

CN112300214A - Palladium compound, preparation method thereof and preparation method of axial chiral biaryl compound

Info

Publication number: CN112300214A
Application number: CN201910681991.7A
Authority: CN
Inventors: 施世良; 申迪
Original assignee: Shanghai Institute of Organic Chemistry of CAS
Current assignee: Shanghai Institute of Organic Chemistry of CAS
Priority date: 2019-07-26
Filing date: 2019-07-26
Publication date: 2021-02-02
Anticipated expiration: 2039-07-26
Also published as: CN112300214B

Abstract

The invention provides a palladium compound, a preparation method thereof and a preparation method of an axial chiral biaryl compound. The invention discloses a compound shown as a formula IV or a formula IV', a palladium compound has a novel structure and is suitable for coupling reaction, and the synthesized axial chiral biaryl compound has various structures, high yield and good stereoselectivity. The invention also discloses a preparation method of the axial chiral biaryl compound, the yield of the axial chiral biaryl compound prepared by the preparation method is high, the reaction stereoselectivity is strong, the ee value can be up to more than 85%, the vast majority is more than 90%, the applicability of the substrate is wide, the compound has good applicability to heterocyclic substrates, and the synthesized axial chiral biaryl compound has various structures.

Description

Palladium compound, preparation method thereof and preparation method of axial chiral biaryl compound

Technical Field

The invention relates to a palladium compound, a preparation method thereof and a preparation method of an axial chiral biaryl compound.

Background

The axial chiral biaryl structure exists in natural products and medicines in great amount. In particular, in the field of asymmetric catalysis, commonly used chiral catalysts such as chiral diols of a binaphthyl structure, monophosphine ligands containing an isoquinoline structure, and the like have an axial chiral biaryl structure. Among the numerous methods for constructing axial chirality, palladium-catalyzed asymmetric Suzuki coupling is considered to be a highly efficient and practical method due to the readily available raw materials and the high stability to water and oxygen. In 2000, Buchwald project group and Cammidge project group simultaneously report the first palladium-catalyzed asymmetric Suzuki coupling reaction to construct axial chiral biaryl compounds, and then a large number of project groups are successively developed in the field. a) Yin, j.j.; buchwald, s.l.j.am.chem.soc.2000,122,12051.b) Cammidge, a.n.; crepy, K.V.L.2000,1723.c) Bermejo, A.; ros, a.; fernandez, r.; lassaletta, j.m.j.am.chem.soc.2008,130,15798.d) Uozumi, y.; matsuura, t.; arakawa, t.; yamada, y.m.a.angelw.chem., int.ed.2009,48,2708.e) Yamamoto, t.; akai, y.; nagata, y.; suginome, m.angelw.chem., int.ed.2011,50,8844.f) Xu, g.; fu, w.; liu, g.; senana yake, c.h.; tang, w.j.am.chem.soc.2014,136,570.g) awai, k.; tatumi, r.; nakahodo, t.; fujihara, h. Firstly, heterocyclic substrates are difficult to construct axial chiral products due to strong coordination ability, weak reactivity, poor stability and low rotational energy barrier of the heterocyclic substrates; secondly, a general catalyst capable of being compatible with various functional groups has not been realized; thirdly, the construction of an ortho-tetra-substituted biaryl compound is still a difficult problem in the asymmetric Suzuki coupling reaction; fourth, the realization of high enantioselectivity in the past often relies on ortho-bulky steric substitution, which also limits the scope of the substrate; fifth, mild reaction conditions and lower catalyst usage remain the goals sought. Sixth, the high enantioselectivity of reactions is mainly achieved by limited chiral phosphine ligands, which also limits the development of such reactions. We assume that a complex formed by a strongly-powered azacyclo-carbene ligand and palladium accelerates oxidative addition and inhibits heterocyclic substrate coordination poisoning, and the highest ee value of the asymmetric Suzuki reaction catalyzed by the chiral azacyclo-carbene-palladium complex at present is only 80%, see h) Benhamou, l.; besnard, c.; kundig, E.P. organometallics.2014,33,260. We developed a series of chiral azacyclo-carbene-palladium complexes, developed an efficient synthesis method for synthesizing an axial chiral biaryl compound by catalyzing asymmetric Suzuki coupling reaction with the chiral azacyclo-carbene-palladium complexes, and the method has important significance for natural product synthesis, axial chiral ligand synthesis and new drug design.

Disclosure of Invention

The invention aims to overcome the defects of low reaction yield, poor stereoselectivity, single substrate structure and the like in the existing palladium-catalyzed coupling reaction for constructing the axial chiral biaryl compound, and provides a palladium compound, a preparation method thereof and a preparation method of the axial chiral biaryl compound. The biaryl compound obtained by the preparation method has the advantages of high yield, good stereoselectivity, various structures and the like.

The invention solves the technical problems through the following technical scheme.

The invention provides a compound shown as a formula IV or a formula IV', which has the following structure:

wherein Ar is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is unsubstituted or R_3a-1Substituted C₆-C₁₄Aryl of (a); each R_3a-1Independently is C₁-C₄Alkyl groups of (a);

R_7a、R_7b、R_7c、R_8a、R_8band R_8cIndependently is hydrogen or C₁-C₄Alkyl groups of (a);

R₅and R₆Independently of one another is hydrogen, C₁-C₄Alkyl, halogen,

Or C₆-C₁₀Aryl of (a); wherein R is_5-1And R_5-2Independently is hydrogen or C₁-C₄Alkyl groups of (a);

is a single bond or a double bond;

or, R₅、R₆Together with the carbon atom to which they are attached to form

In a preferred embodiment of the present invention, when Ar is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄When aryl of (A) is said R_3a-1May independently be one or more, for example 1,2, 3 or 4, when there are more than one R_3a-1When R is said_3a-1May be the same or different.

In a preferred embodiment of the present invention, when Ar is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is unsubstituted or R_3a-1Substituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) is independently C₆-C₁₀Aryl of (b), preferably phenyl or naphthyl, more preferably phenyl.

In a preferred embodiment of the invention, when R is_3a-1Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, preferably methyl or tert-butyl, more preferably tert-butyl.

In a preferred embodiment of the invention, when R is_7a、R_7b、R_7c、R_8a、R_8bAnd R_8cIndependently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, preferably methyl.

In a preferred embodiment of the invention, when R is₅、R₆、R_5-1And R_5-2Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.

In a preferred embodiment of the invention, when R is₅And R₆When independently halogen, the halogen is independently F, Cl, Br or I.

In a preferred embodiment of the invention, when R is₅And R₆Independently is C₆-C₁₀Aryl of (2), said C₆-C₁₀Aryl of (a) is independently phenyl or naphthyl.

In a preferred embodiment of the present invention, when Ar is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄When aryl of (A) is said R_3a-1Substituted C₆-C₁₀Aryl of (A) is independently preferred

In a preferred embodiment of the invention, certain groups of the compounds of formula IV or IV' are defined as follows (undefined groups are as defined in any of the preceding schemes): ar (Ar)_3a、Ar_3b、Ar_3cAnd Ar_3dThe same is true.

In a preferred embodiment of the present invention, certain groups of the compounds of formula IV are defined as follows (undefined groups are as defined in any of the preceding schemes): ar (Ar)_3a、Ar_3b、Ar_3cAnd Ar_3dSame as Ar_3a、Ar_3b、Ar_3cAnd Ar_3dIs R_3a-1Substituted C₆-C₁₄Aryl group of (1).

In a preferred embodiment of the invention, certain groups of the compounds of formula IV or IV' are defined as follows (undefined groups are as defined in any of the preceding schemes): r_7a、R_7c、R_8aAnd R_8cSame as R_7bAnd R_8bThe same is true.

In a preferred embodiment of the invention, certain groups of the compounds of formula IV or IV' are defined as follows (undefined groups are as defined in any of the preceding schemes): r_7a、R_7c、R_8aAnd R_8cIs hydrogen, R_7bAnd R_8bSame as R_7bAnd R_8bIs C₁-C₄Alkyl group of (1).

In a preferred embodiment of the invention, certain groups of the compounds of formula IV or IV' are defined as follows (undefined groups are as defined in any of the preceding schemes):

Ar_3a、Ar_3b、Ar_3cand Ar_3dIndependently is unsubstituted or R_3a-1Substituted C₆-C₁₄Aryl of (a); each R_3a-1Independently is C₁-C₄Alkyl groups of (a);

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R_7a、R_7c、R_8aand R_8cIs hydrogen, R_7bAnd R_8bIndependently is C₁-C₄And R is alkyl of_7bAnd R_8bThe same;

R₅and R₆Is hydrogen;

is a single bond or a double bond;

or, R₅And R₆Together with the carbon atom to which they are attached to form

Ar_3a、Ar_3b、Ar_3cand Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄Aryl of (a); each R_3a-1Independently is C₁-C₄Alkyl groups of (a);

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R₅and R₆Is hydrogen;

is a single bond or a double bond;

Ar_3a、Ar_3b、Ar_3cand Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄Aryl of (a); each R_3a-1Independently is C₁-C₄Alkyl groups of (a), preferably tert-butyl;

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R₅and R₆Is hydrogen;

is a single bond.

In a preferred embodiment of the present invention, the formula IV can be any of the following structures:

in a preferred embodiment of the present invention, the formula IV' can be any of the following structures:

the invention also provides a crystal form of the compound IV-1((R, R, R, R) - (DTB-SIPE) Pd (cin) Cl) or the compound IV-3((R, R, R) - (SIPE) Pd (cin) Cl), in a single crystal X-ray diffraction spectrum using a radiation source of Ga-Ka,

the single crystal of the compound IV-1 belongs to an orthorhombic system, and the space group isP2₁2₁2₁The unit cell parameters are as follows:

α＝90°，

β＝90°，

gamma 90 deg., unit cell volume

The number of asymmetric units in the unit cell, Z, is 4, and the single crystal parameters can be those in table 1;

the single crystal of the compound IV-3 belongs to an orthorhombic system, and the space group is P2₁2₁2₁The unit cell parameters are as follows:

α＝90°，

β＝90°，

gamma 90 deg., unit cell volume

The number of asymmetric units in the unit cell, Z, is 4, and the single crystal parameters can be those in table 2;

single crystal parameters:

TABLE 1 Single Crystal data for Compound IV-1(R, R, R, R) - (DTB-SIPE) Pd (cin) Cl

TABLE 2 Single Crystal data for Compound IV-3(R, R, R, R) - (SIPE) Pd (cin) Cl

The invention also provides a preparation method of the single crystal of the compound IV-1 or the compound IV-3, which comprises the following steps: and (3) forming a solution by the compound IV-1 or the compound IV-3 and a chloralkane solvent, filtering, and standing the filtrate in the atmosphere of the alkane solvent to obtain the single crystal.

The operation of leaving the filtrate still in the atmosphere of the alkane solvent preferably comprises the steps of: the filtrate is placed in a container of the alkane solvent and allowed to stand, and more preferably, the filtrate is placed in a jar containing the alkane solvent and allowed to stand.

The chloroalkane solvent may be a conventional chloroalkane solvent in the art, preferably chloroform and/or dichloromethane, e.g., chloroform. The amount of the chloroalkane solvent is not particularly limited as long as the compound IV-1 or the compound IV-3 can be dissolved to obtain a clear and transparent solution. Generally, the volume mass ratio of the chloroalkane solvent to the compound IV-1 or the compound IV-3 is 0.1-0.5L/g, for example: 0.2L/g.

The alkane solvent may be any alkane solvent conventional in the art, preferably n-pentane and/or n-hexane, e.g., n-hexane.

The filtration may be conventional filtration in the art for such operations, preferably filtration with a filter membrane.

The method for preparing a single crystal may further comprise the step of selecting the single crystal under a microscope after the single crystal is grown.

The invention provides a preparation method of a compound shown as a formula IV or a formula IV', which comprises the following steps: in an organic solvent, under the action of alkali, a compound shown as a formula V or a formula V' and a compound shown as a formula VI are subjected to a reaction shown as follows;

wherein Ar is_3a、Ar_3b、Ar_3c、Ar_3d、R₅、R₆、R_7a、R_7b、R_7c、R_8a、R_8b、R_8cAnd

all as described above.

In the preparation method of the compound shown in the formula IV or the formula IV', the reaction conditions and operation can be the conditions and operation which are conventional in the reaction in the field.

The invention provides a preparation method of a compound 1, which comprises the following steps: in a solvent, under the action of a palladium compound and alkali, carrying out coupling reaction on a compound shown as a formula II and a compound shown as a formula III as shown in the specification; the compound 1 is a compound shown in a formula I or a compound shown in a formula I';

wherein the content of the first and second substances,

x is Cl, Br, I, OTs or OTf;

y is B (OH)₂、

Or BF₃K；

Ar₁And Ar₂Independently is C₆-C₁₄Or a 5-14 membered heteroaryl group having one or more heteroatoms selected from N, O and S, and 1-4 heteroatoms;

Z₁、Z₂、Z₃、W₁、W₂and W₃Independently is N or CR;

each R, R₁、R₂、R₃And R₄Independently hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R_1-1Substituted C₁-C₄Alkyl of (a), unsubstituted or R_1-2Substituted C₁-C₄Alkoxy of (A), unsubstituted or R_1-3Substituted C₆-C₁₄Aryl of (A), unsubstituted or R_1-4C with substituted heteroatom (S) selected from N, O and S, and heteroatom number of 1-4₅-C₁₄The heteroaryl group of,

Each R_1-1、R_1-2、R_1-3And R_1-4Independently of one another, halogen, C₁-C₄Alkyl of (C)₁-C₄Alkoxy of, or C₆-C₁₄Aryl of (a);

each R_1-5Independently is hydroxy, C₁-C₄Alkyl or C₁-C₄Alkoxy group of (a);

each R_1-6And R_1-7Independently is hydrogen or C₁-C₄Alkyl groups of (a);

or, R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form unsubstituted or R together with the carbon atom to which they are attached_aSubstituted C₆-C₁₄Or unsubstituted or R_bA 5-14 membered heteroaryl group having 1-4 heteroatoms as one or more hetero atoms selected from N, O and S;

each R_aAnd R_bIndependently is hydroxyl, aldehyde group, amino, nitro, cyano, halogen, unsubstituted or R_a-1Substituted C₁-C₄Alkyl of (a), unsubstituted or R_a-2Substituted C₁-C₄Alkoxy group of,

Each R_a-1And R_a-2Independently of one another, halogen, C₁-C₄Alkyl of (C)₁-C₄Alkoxy of, or C₆-C₁₄Aryl of (a);

each R_a-3Independently is hydroxy, C₁-C₄Alkyl or C₁-C₄Alkoxy group of (a);

each R_a-4And R_a-5Independently is hydrogen or C₁-C₄Alkyl groups of (a);

the palladium compound is a compound shown as a formula IV or IV',

wherein Ar is_3a、Ar_3b、Ar_3c、Ar_3d、R₅、R₆、R_7a、R_7b、R_7c、R_8a、R_8bAnd R_8cAre all as described above;

when the palladium complex is

When the compound 1 is the compound shown in the formula I;

when the palladium complex is

When the compound 1 is the compound shown in the formula I ', the compound is the compound shown in the formula I'.

In a preferred embodiment of the present invention, when Ar is₁Is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (a), such as phenyl or naphthyl, preferably phenyl;

in a preferred embodiment of the present invention, when Ar is₁When the 5-14 membered heteroaryl group having "one or more hetero atoms selected from N, O and S and 1-4 hetero atoms" is a 5-14 membered heteroaryl group, the 5-14 membered heteroaryl group is a 5-6 membered monocyclic heteroaryl group or a 6-14 membered fused heteroaryl group, preferably a 5-6 membered monocyclic heteroaryl groupHeteroaryl, said 5-6 membered monocyclic heteroaryl may be furyl, thienyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, preferably pyridyl.

In a preferred embodiment of the present invention, when Ar is₂Is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (a), such as phenyl or naphthyl, preferably phenyl;

in a preferred embodiment of the present invention, when Ar is₂When the 5-14 membered heteroaryl group is a 5-14 membered heteroaryl group having "one or more heteroatoms selected from N, O and S and 1-4 heteroatoms", the 5-14 membered heteroaryl group is a 5-6 membered monocyclic heteroaryl group, or a 6-14 membered fused heteroaryl group, preferably a 5-6 membered monocyclic heteroaryl group, and the 5-6 membered monocyclic heteroaryl group may be furyl, thienyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, preferably pyridyl.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently halogen, said halogen is independently F, Cl, Br or I, preferably F.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-1Substituted C₁-C₄When said alkyl is (a), said R_1-1May independently be one or more, for example 1,2 or 3, when a plurality of R's are present_1-1When R is said_1-1May be the same or different.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-1Substituted C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) may be independently a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl group, preferably a methyl group.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-2Substituted C₁-C₄When it is an alkoxy group, said R_1-2May independently be one or more, for example 1,2 or 3, when a plurality of R's are present_1-2When R is said_1-2May be the same or different.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-2Substituted C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) may be independently methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-3Substituted C₆-C₁₄When aryl of (A) is said R_1-3May independently be one or more, for example 1,2, 3 or 4, when there are more than one R_1-3When R is said_1-3May be the same or different.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-3Substituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) may independently be C₆-C₁₀Aryl of (2), preferably phenyl or naphthyl.

In a preferred embodiment of the invention, when R is_1-1、R_1-2、R_1-3And R_1-4Independently halogen, said halogen is independently F, Cl, Br or I, preferably F.

In a preferred embodiment of the invention, when R is_1-1、R_1-2、R_1-3、R_1-4、R_1-5、R_1-6And R_1-7Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) may be independently a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl group, preferably a methyl group.

In a preferred embodiment of the invention, when R is_1-1、R_1-2、R_1-3、R_1-4And R_1-5Independently is C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) may be independently methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy.

In a preferred embodiment of the invention, when R is_1-1、R_1-2、R_1-3、R_1-4Independently is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) may independently be C₆-C₁₀Aryl of (b), preferably phenyl.

In a preferred embodiment of the invention, when R is_1-5、R_1-6And R_1-7Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) is independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, preferably methyl or ethyl.

In a preferred embodiment of the invention, when R is_1-5Is C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) is methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy or ethoxy.

In a preferred embodiment of the invention, when R is₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form R together with the carbon atom to which it is attached_aSubstituted C₆-C₁₄When aryl of (A) is said R_aMay independently be one or more, for example 1,2 or 3, when a plurality of R's are present_aWhen R is said_aMay be the same or different.

In a preferred embodiment of the invention, when R is₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form unsubstituted or R together with the carbon atom to which they are attached_aSubstituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (2), preferably phenyl or naphthyl.

In a preferred embodiment of the invention, when R is₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form R together with the carbon atom to which it is attached_bWhen the substituted 'heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-4', the R is_bMay independently be one or more, for example 1,2 or 3, when a plurality of R's are present_bWhen R is said_bMay be the same or different.

In a preferred embodiment of the invention, when R is₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form unsubstituted or R together with the carbon atom to which they are attached_bWhen the substituted "hetero atom" is one or more selected from N, O and S, and the number of hetero atoms is 1 to 4 ", and the 5-to 14-membered heteroaryl group is a 5-to 6-membered monocyclic heteroaryl group or a 6-to 14-membered fused heteroaryl group, preferably a 5-to 6-membered monocyclic heteroaryl group. The 5-6 membered monocyclic heteroaryl group can be furyl, thienyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl, preferably thienyl, pyrrolyl, pyridyl or pyrimidinyl, for example

The 6-14 membered fused heteroaryl group can be a 6-10 membered fused heteroaryl group, such as indolyl, isoindolyl, quinolinyl, isoquinolinyl, preferably indolyl, e.g.

In a preferred embodiment of the invention, when R is_aAnd R_bWhen independently halogen, the halogen is independently F, Cl, Br or I.

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is R_a-1Substituted C₁-C₄When said alkyl is (a), said R_a-1May independently be one or more, for example 1,2 or 3, when a plurality of R's are present_a-1When R is said_a-1May be the same or different.

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is unsubstituted or R_a-1Substituted C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) may be independently a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group.

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is R_a-2Substituted C₁-C₄When it is an alkoxy group, said R_a-2May independently be one or more, for example 1,2 or 3, when a plurality of R's are present_a-2When R is said_a-2May be the same or different.

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is unsubstituted or R_a-2Substituted C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) may be independently methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.

In a preferred embodiment of the invention, when R is_a-1And R_a-2When independently halogen, the halogen is independently F, Cl, Br or I.

In a preferred embodiment of the invention, when R is_a-1、R_a-2、R_a-3、R_a-4And R_a-5Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) may be independently a methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl group, preferably a methyl or ethyl group.

In a preferred embodiment of the invention, when R is_a-1、R_a-2And R_a-3Independently is C₁-C₄Alkoxy of (2), said C₁-C₄Alkoxy group ofAnd independently a methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy group, preferably a methoxy group.

In a preferred embodiment of the invention, when R is_a-1And R_a-2Independently is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (A) may be C₆-C₁₀Aryl of (2), for example phenyl.

In a preferred embodiment of the invention, when R is_a-3、R_a-4And R_a-5Independently is C₁-C₄When there is an alkyl group, said C₁-C₄The alkyl group of (a) may be independently a methyl group, an ethyl group, a propyl group, an isopropyl group, a n-butyl group, an isobutyl group, a sec-butyl group or a tert-butyl group.

In a preferred embodiment of the invention, when R is_a-3Is C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) may be independently methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-1Substituted C₁-C₄When said alkyl is (a), said R_1-1Substituted C₁-C₄Is independently preferably-CF₃。

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-2Substituted C₁-C₄When it is an alkoxy group, said R_1-2Substituted C₁-C₄Alkoxy of (A) is independently preferably-OBn or

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is R_1-3Substituted C₆-C₁₄When aryl of (A) is said R_1-3Substituted C₆-C₁₄Aryl of (A) is independently preferred

In a preferred embodiment of the present invention, when R, R₁、R₂、R₃And R₄Independently is

When it is used, the

Independently preferably

When it is used, the

Independently preferably

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is

Said

Preference is given to

In a preferred embodiment of the invention, when R is_aAnd R_bIndependently is

When it is used, the

Preference is given to

In a preferred embodiment of the invention, certain groups of the compounds of formula I or formula I' are defined as follows (undefined groups are as defined in any of the preceding schemes):

x is Cl, Br or OTf;

y is B (OH)₂BPin, Bneo or BF₃K；

Ar₁And Ar₂Independently is C₆-C₁₄Aryl of (a);

Z₁、Z₂、Z₃、W₁、W₂and W₃Independently is N or CR;

each R, R₁、R₂、R₃And R₄Independently hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R_1-1Substituted C₁-C₄Alkyl of (a), unsubstituted or R_1-2Substituted C₁-C₄Or unsubstituted or R_1-3Substituted C₆-C₁₄Aryl of (a);

each R_1-1、R_1-2、R_1-3And R_1-4Independently of one another, halogen, C₁-C₄Alkyl of, or C₁-C₄Alkoxy group of (a);

each R_1-5Independently is C₁-C₄Alkyl or C₁-C₄Alkoxy group of (a);

each R_1-6And R_1-7Independently is hydrogen or C₁-C₄Alkyl groups of (a);

or, R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Is connected with itIndependently together form unsubstituted or R_aSubstituted C₆-C₁₄Or unsubstituted or R_bA 5-14 membered heteroaryl group having 1-4 heteroatoms as one or more hetero atoms selected from N, O and S;

each R_aAnd R_bIndependently hydroxyl, aldehyde group, amino, nitro, cyano, halogen, unsubstituted C₁-C₄Alkyl, unsubstituted C₁-C₄Alkoxy of (5), or

Each R_a-3Independently is C₁-C₄Alkyl or C₁-C₄Alkoxy group of (2).

In a preferred embodiment of the present invention, the compound represented by formula I or formula I' may have any one of the following structures:

in the coupling reaction, the solvent may be an organic solvent or a mixed solvent of an organic solvent and water. The organic solvent is preferably one or more of an alcohol solvent, an aromatic solvent and an ether solvent, and more preferably an alcohol solvent and/or an aromatic solvent. The alcohol solvent is preferably one or more of ethanol, isopropanol and tert-butanol, and more preferably tert-butanol. The aromatic hydrocarbon solvent is preferably toluene. The ethereal solvent is preferably Tetrahydrofuran (THF). When the solvent is a mixed solvent of an organic solvent and water, the volume ratio of the organic solvent to the water is preferably 5:1 to 10:1, more preferably 8:1 to 10:1, for example 9: 1.

In the coupling reaction, the base is preferably one or more of alkali metal hydroxide, alkali metal carbonate, alkali metal phosphate and alkali metal alkoxide, and more preferably alkali metal hydroxide. The alkali metal hydroxide is preferably potassium hydroxide. The alkali metal carbonate is preferably potassium carbonate and/or cesium carbonate. The alkali metal phosphate is preferably potassium phosphate. The alkali metal alkoxide is preferably potassium methoxide and/or potassium tert-butoxide, and potassium tert-butoxide is more preferred.

In the coupling reaction, the molar ratio of the compound shown in the formula III to the compound shown in the formula II is preferably 1:1-5:1, more preferably 1:1-2:1, such as 1.2:1, 1.3:1 or 2: 1.

In the coupling reaction, the molar ratio of the base to the compound shown in the formula II is preferably 1: 1-1: 1, more preferably 1:1-3:1, such as 1.3:1, 2:1 or 2.5: 1.

In the coupling reaction, the molar concentration of the compound shown in the formula II in the solvent is preferably 0.1-0.5mol/L, more preferably 0.1-0.3mol/L, such as 0.2mol/L or 0.25 mol/L.

In the coupling reaction, the molar ratio of the palladium complex to the compound shown in the formula II is preferably 1:10-1:500, more preferably 1:50-1:200, such as 1:50, 1:100 or 1: 200.

In the coupling reaction, the coupling reaction temperature is preferably 30-60 ℃. For example 30 ℃,50 ℃ or 60 ℃.

In the coupling reaction, the progress of the coupling reaction can be monitored by means conventional in the art (e.g., TLC, HPLC or LC-MS), and the coupling reaction time is preferably 24-48 h.

The coupling reaction is preferably carried out under an atmosphere of protective gas, which may be a protective gas conventional in the art, such as nitrogen.

In the coupling reaction, after the reaction is finished, the method may further comprise a post-treatment operation, and the post-treatment may comprise the following steps: and separating and purifying the reaction solution to obtain the catalyst. The separation and purification is preferably column chromatography separation.

In the present invention, the term halogen means fluorine, chlorine, bromine, or iodine.

In the present invention, the term alkyl is a branched or straight chain saturated aliphatic hydrocarbon group having the specified number of carbon atoms; for example, said C₁-C₄The alkyl is methyl, ethyl or n-propylIsopropyl, n-butyl, tert-butyl or isobutyl.

In the present invention, the term alkoxy represents a group formed by bonding an alkyl group to an oxygen atom, i.e.) "

", R is alkyl. C₁-C₄The alkoxy group of (A) means a methoxy group, an ethoxy group, an n-propoxy group, an isopropoxy group, an n-butoxy group, an isobutoxy group or a tert-butoxy group.

In the present invention, the term "aryl" refers to an aromatic group having the specified number of carbon atoms, preferably a monocyclic, bicyclic or tricyclic aromatic group, each of which, when bicyclic or tricyclic, satisfies the Huckel rule. C of the invention_6-10The aryl group of (b) means an aromatic group having 6 to 10 carbon atoms, such as phenyl or naphthyl.

In the present invention, the term heteroaryl denotes a stable monocyclic, bicyclic or tricyclic ring of up to 14 atoms in each ring, wherein at least one ring is aromatic and contains 1 to 4 heteroatoms selected from O, N and S. Heterocyclic aryl groups within the scope of this definition include 5-6 membered monocyclic heteroaryl, 6-14 membered fused heteroaryl. 5-6 membered monocyclic heteroaryl groups include, but are not limited to: furyl, thienyl, pyrazolyl, pyrrolyl, pyridazinyl, pyridyl, pyrimidinyl, oxazolyl, isoxazolyl, and the like. 6-14 membered fused heteroaryl groups include monocyclic heteroaryl fused to aryl, heteroaryl, cycloalkyl or heterocycloalkyl, examples include, but are not limited to, acridinyl, carbazolyl, cinnolinyl, quinoxalinyl, indolyl, isoindolyl, benzopyrazolyl, benzothiophenyl, benzofuranyl, quinolinyl, isoquinolinyl, pyrrolopyridinylpyrazinyl, tetrahydroquinoline or heterocycloalkyl

On the basis of the common knowledge in the field, the above preferred conditions can be combined randomly to obtain the preferred embodiments of the invention.

The reagents and starting materials used in the present invention are commercially available.

The positive progress effects of the invention are as follows:

(1) the axial chiral biaryl compound prepared by the preparation method has high yield and strong reaction stereoselectivity, and the ee value can be up to more than 85 percent, and the vast majority is more than 90 percent.

(2) The preparation method has wide applicability of the substrate, has good applicability to heterocyclic substrates, and the synthesized axial chiral biaryl compound has various structures.

(3) The palladium compound has a novel structure, is suitable for coupling reaction, and the synthesized axial chiral biaryl compound has various structures, high yield and good stereoselectivity.

Drawings

FIG. 1 is a single crystal diagram of Compound IV-1.

FIG. 2 is a single crystal diagram of Compound IV-3.

FIG. 3 is a single crystal diagram of Compound I-4.

Detailed Description

The invention is further illustrated by the following examples, which are not intended to limit the scope of the invention. The experimental methods without specifying specific conditions in the following examples were selected according to the conventional methods and conditions, or according to the commercial instructions.

Preparation of compound A series compounds

Example 1:1, 3-bis (2, 6-bis ((R) -1- (3, 5-di-tert-butylphenyl) ethyl) -4-methylphenyl) -4, 5-dihydro-1H-imidazolium salt (Compound V-1)

Step 1: synthesis of (Z) -N, N' -bis (4-methoxy-2, 6-bis ((S) -1-phenylethyl) phenyl) ethylene-1, 2-diamine 2- (1- (3, 5-di-tert-butylphenyl) vinyl) -4,4,5, 5-tetramethyl-1, 3, 2-dioxolane (intermediate 2)

1, 3-bis (diphenylphosphinopropane) nickel dichloride (2.48g, 4.6mmol), tetrahydrofuran (100 mL) and diisobutylaluminum hydride (122mL, 183.1mmol) are added into a 500mL round-bottom flask, the reaction is cooled to 0 ℃, the intermediate 1 is dissolved in tetrahydrofuran (100 mL), the mixture is slowly dripped into the reaction solution, the reaction solution is transferred to room temperature and stirred for 2 hours after the dripping is finished, the reaction is cooled to 0 ℃, 2-methoxy-4, 4,5, 5-tetramethyl-1, 3, 2-dioxolane (30mL, 228.9mmol) is slowly dripped, and the reaction solution is transferred to an 80 ℃ oil bath and heated and stirred for 24 hours. Stopping the reaction, transferring the reaction solution to a cold trap at 0 ℃, slowly dropwise adding water to quench the reaction, removing part of tetrahydrofuran solution under reduced pressure, adding a proper amount of ethylene diamine tetraacetic acid aqueous solution and ethyl acetate solution, stirring for 3 hours, extracting ethyl acetate, drying an organic phase by anhydrous sodium sulfate, concentrating, and purifying by column chromatography to obtain an oily intermediate 2(44.5g, yield 85%).

Step 2: synthesis of 2, 6-bis (1- (3, 5-di-tert-butylphenyl) vinyl) -4-methylaniline (intermediate 4)

A100 mL pressure bottle was charged with 2, 6-dibromo-4-methylaniline (43.9g,128.3mmol), [1, 3-bis (2, 6-diisopropylbenzene) imidazole-2-ylidene ] (3-chloropyridine) palladium dichloride (729mg,1.2mmol), potassium hydroxide (9.8g,174.9mmol), intermediate 2(15.4g,58.3mol), and 100mL of a tetrahydrofuran solution, and heated at 100 ℃ for 12 hours. The reaction was stopped, column was washed with ethyl acetate, concentrated under reduced pressure and purified by column chromatography to give intermediate 4(27g, 87% yield) as a pale solid

And step 3: synthesis of 2, 6-bis ((R) -1- (3, 5-di-tert-butylphenyl) ethyl) -4-methylaniline (intermediate 5)

To a 300mL reaction vial was added intermediate 4(18.5g,34.5mmol),120mL MeOH, and another dry vial was added rhodium bis (norbornadiene) tetrafluoroborate ((NBD)₂RhBF₄0.3 mol%), (Rc, Sp) -DuanPhos (0.36 mol%), DCM (12mL) was stirred for 15min and added to a 300mL reaction flask, and the mixture was purged with 80atm H at 30 deg.C₂After 48 hours of the reaction, the reaction was stopped. Methanol was removed under reduced pressure, the mixture was passed through a short silica gel column, washed with ethyl acetate, and concentrated and then purified by column chromatography to obtain intermediate 5(13.0g, yield 70%) as an oil.¹H NMR(400MHz,CDCl₃)δ:7.22(t,J＝1.8Hz,2H),7.02(d,J＝1.9Hz,4H),6.97(s,2H),4.02(q,J＝7.1Hz,2H),3.29(s,2H),2.33(s,3H),1.59(d,J＝7.2Hz,6H),1.25(s,36H)。¹³C NMR(101MHz,Chloroform-d)δ150.7,144.8,139.6,130.6,126.8,126.2,121.8,120.1,41.1,34.9,31.6,24.9,22.2,21.3.

And 4, step 4: synthesis of N, N-bis (2, 6-bis ((R) -1- (3, 5-di-t-butylphenyl) ethyl) -4-methylphenyl) oxamide (Compound 6)

To a 50mL round bottom flask of intermediate 5(1.89g,3.5mol), tetrahydrofuran 15mL, triethylamine (535. mu.L, 3.9mol), the reaction was cooled to 0 deg.C, oxalyl chloride (163. mu.L, 1.9mol) was slowly added dropwise, the reaction was allowed to warm to room temperature, and stirring was continued overnight. The reaction was stopped, and a suitable amount of saturated aqueous sodium bicarbonate was added to the reaction solution to quench the reaction, followed by extraction with dichloromethane, drying the organic phase over anhydrous sodium sulfate, concentration, purification by column chromatography, and isolation to give intermediate 6 as a white foam (1.68g, yield 85%).¹H NMR(400MHz,CDCl3)δ:8.58(s,2H),7.25–7.20(m,4H),7.08(d,J＝1.8Hz,8H),6.93(s,4H),4.23(q,J＝7.0Hz,4H),2.27(s,6H),1.54(d,J＝7.1Hz,6H),1.26(s,72H),0.93(d,J＝6.6Hz,6H).¹³C NMR(101MHz,CDCl3)δ:201.6,159.2,150.4,144.3,137.7,128.4,126.4,122.1,120.0,40.3,34.8,31.5,31.4,3.,24.9,22.2,21.7.

HRMS (ESI) calculated value (C)₈₀H₁₁₆N₃O₂[M+H]+)1150.9062, found 1150.9054.

And 5: synthesis of N, N-bis (2, 6-bis ((R) -1- (3, 5-di-tert-butylphenyl) ethyl) -4-methylphenyl) ethane-1, 2-diamine (intermediate 7)

To 100mL of intermediate 6(3g,2.65mol) and 30mL of tetrahydrofuran in a round-bottomed flask, the reaction solution was cooled to 0 ℃, lithium aluminum hydride (540.0mg,13.5mol) was added in portions, the reaction solution was heated to reflux, and stirring was continued for 24 h. Stopping the reaction, adding 15% potassium hydroxide water into the reaction solutionQuenching the solution (0.5mL) for reaction, stirring at room temperature for 15min, adding a proper amount of magnesium sulfate, carrying out suction filtration, washing with ethyl acetate, drying the organic phase with anhydrous sodium sulfate, and concentrating; the above-mentioned dried mixture was dissolved in 30mL of a toluene solution, and BH was added dropwise thereto₃Me2S (5.4mL.2.0M in THF,10.8mmol), was stirred at reflux for 12 h. After the reaction was terminated, 1M hydrochloric acid (20mL) was slowly added to the reaction solution, and the mixture was stirred for 3 hours, extracted with dichloromethane, and the organic phase was further made alkaline with an aqueous sodium hydroxide solution, dried and concentrated to obtain intermediate 7(1.8g, yield 62%) as a white solid.¹H NMR(400MHz,CDCl₃)δ:7.22(t,J＝1.8Hz,4H),7.12(d,J＝1.9Hz,8H),7.01(s,4H),4.62(q,J＝7.1Hz,4H),3.12(d,J＝7.2Hz,2H),2.60(d,J＝7.5Hz,2H),2.35(s,6H),1.65(d,J＝7.1Hz,12H),1.25(s,72H)..¹³C NMR(101MHz,CDCl₃)δ:150.3,145.6,142.5,140.9,132.4,126.4,121.9,119.6,77.4,77.1,76.7,53.4,51.9,39.7,34.8,31.5,23.4,21.5.

HRMS (ESI) calculated value (C)₈₀H₁₁₇N₂[M+H]⁺)1105.9211, found 1105.9201.

Step 6: synthesis of 1, 3-bis (2, 6-bis ((R) -1- (3, 5-di-t-butylphenyl) ethyl) -4-methylphenyl) -4, 5-dihydro-1H-imidazolium salt (Compound V-1)

To a 50mL eggplant-shaped bottle was added compound 7(1.5g,2.35mmol), NH₄Cl (108.6mg, 2.03mmol), 4.7mL triethyl orthoformate, under nitrogen substitution, the mixture was reacted at 115 ℃ for 20 hours, passed through a short silica gel column, concentrated and purified by column chromatography to isolate white compound V-1(1.4g, yield 90%).¹H NMR(400MHz,CDCl₃)δ:8.24(s,1H),7.29(d,J＝2.2Hz,4H),7.04(s,4H),6.92(t,J＝1.9Hz,8H),4.49–4.32(m,4H),4.20(d,J＝11.4Hz,2H),3.89(q,J＝7.0Hz,2H),2.31(s,6H),1.84(d,J＝7.0Hz,6H),1.30(s,36H),1.19(s,36H),1.06(d,J＝7.1Hz,6H).¹³C NMR(101MHz,CDCl3)δ:158.5,151.3,151.0,144.0,143.6,143.4,143.1,141.5,128.6,128.3,128.0,121.6,121.1,120.9,120.8,77.4,77.0,76.7,54.1,40.4,38.7,34.9,34.9,31.5,31.5,23.2,22.9,21.7。

HRMS (ESI) calculated value (C)₈₁H₁₁₅N₂[M+H]⁺)1115.9055, found 1115.9038.

Referring to the method of example 1, compounds V-2 to V-7 were synthesized using different starting materials:

example 2: synthesis of palladium complexes

General procedure A

Wherein Ar is_3a、Ar_3b、Ar_3c、Ar_3d、R₅、R₆、R_7a、R_7b、R_7c、R_8a、R_8bAnd R_8cAll as described above.

In a glove box, compound V (0.3mmol), potassium tert-butoxide (30.3mg,0.27mmol) and tetrahydrofuran (1.2mL,0.25M) were added in that order to an 8mL vial and stirred at room temperature for 4 h. Then [ Pd (eta) ]³-cin)(μ-Cl)]₂(77.7mg,0.15mmol) was added and stirring continued at room temperature for 12 h. Stopping the reaction, passing the reaction solution through a short silica gel column, washing with ethyl acetate, concentrating the organic phase, and purifying by column chromatography to obtain a light yellow solid.

Example 3: synthesis of Palladium Complex (R, R, R, R) - (DTB-SIPE) Pd (cin) Cl (Compound IV-1)

According to general procedure A, compound V-1(345.2mg,0.3mmol) was added to an 8mL vial and isolated as a pale yellow solid279.8mg of a solid (yield: 68%, compound IV-1).¹H NMR(400MHz,CDCl₃)δ:7.49(s,4H),7.33–7.28(m,3H),7.22(m,1H),7.17(m,2H),7.09(m,3H),7.07–6.95(m,8H),5.07(s,1H),4.73(d,J＝7.8Hz,2H),4.20(m,1H),3.33(m,2H),2.80(m,2H),2.41(s,6H),1.72(m,12H),1.38(s,2H),1.35–1.26(s,36H),1.21(s,36H),1.18(s,2H).¹³C NMR(101MHz,CDCl₃)δ:150.8,150.2,147.3,144.3,143.5,143.1,138.3,136.9,135.8,128.8,128.2,127.8,127.1,126.3,123.2,121.5,120.0,119.5,111.3,92.6,52.7,44.9,40.95,39.6,35.0,34.8,31.7,31.5,26.3,25.2,21.8.

HRMS (MALDI) calculated value (C)₉₀H₁₂₃N₂Pd[M-Cl]⁺)1337.8743 found 1337.8721

Example 4: synthesis of Palladium Complex (R, R, R, R) - (DM-SIPE) Pd (cin) Cl (Compound IV-2)

According to the general procedure A, compound V-2(55.2mg,0.06mmol) was added to an 8mL vial and isolated as a yellow foamy solid 37.1mg (yield: 60%, compound IV-2).¹H NMR(400MHz,CDCl₃)δ:7.39–7.23(m,6H),7.21–7.00(m,7H),6.87(m,5H),6.77(m,3H),4.73(m,4H),4.00–3.66(m,1H),3.21(m,2H),2.53(s,2H),2.44(s,6H),2.35(s,6H),2.22(s,12H),2.12(s,1H),1.76(d,J＝7.1Hz,6H),1.64(d,J＝7.0Hz,6H).¹³C NMR(101MHz,CDCl₃)δ:208.9,148.2,144.9,142.8,138.2,137.6,136.2,128.6,128.2,128.0,127.9,127.8,127.4,126.7,126.6,125.0,110.5,93.5,53.4,45.3,41.2,38.5,25.9,25.5,22.1,21.8,21.7,21.6,21.5,14.3.

HRMS (MALDI) calculated value (C)₆₆H₇₅N₂Pd[M-Cl]⁺)997.4981, found 997.4924.

Example 5: synthesis of Palladium Complex (R, R, R, R) - (SIPE) Pd (cin) Cl (Compound IV-3)

According to general method A, compound V-3(420.0mg,0.6mmol) is added to an 8mL vial, and 430.2mg of a light-colored solid is isolated (yield: 77%, compound IV-3).¹H NMR(400MHz,CDCl₃)δ:7.67(m,4H),7.39(t,J＝7.6Hz,2H),7.28(m,7H),7.24–7.09(m,14H),6.88(d,J＝11.4Hz,2H),4.94–4.45(m,5H),4.29(m,1H),3.22(m,2H),2.46(m,2H),2.38(m,6H),1.77(m,6H),1.62(s,6H).¹³C NMR(101MHz,CDCl₃)δ:147.9,147.9,145.0,142.3,137.9,136.1,128.9,128.7,128.5,128.3,128.1,127.5,127.4,127.1,126.2,126.1,109.8,109.1,95.2,92.2,77.3,53.3,44.1,41.2,41.0,38.2,25.0,24.2,24.0,21.8.

HRMS (ESI) calculated value (C)₅₈H₅₉N₂Pd[M-Cl]⁺)885.3729, found 885.3695.

Example 6: synthesis of Palladium Complex (R, R, R, R) - (DTB-SIPE) Pd (cin) Cl (Compound IV-4)

According to general method A, compound V-4(127.0mg,0.1mmol) is added to an 8mL vial and 430.2mg of a yellow solid is isolated (yield: 77%, compound IV-4).¹H NMR(400MHz,CDCl₃)δ:7.62(s,2H),7.57(s,3H),7.38(s,2H),7.34–7.25(m,3H),7.22(m,4H),7.02(s,2H),6.80–6.69(m,7H),6.03(d,J＝6.9Hz,2H),5.21(s,2H),4.84(s,1H),4.52(d,J＝12.8Hz,1H),4.21–4.11(m,2H),2.56(s,6H),2.08(s,1H),1.64(m,12H),1.40(s,36H),0.89(s,36H).¹³C NMR(101MHz,CDCl₃)δ:150.4,145.0,145.0,144.2,143.5,142.8,140.5,138.4,138.2,133.9,128.9,128.6,128.1,127.4,126.7,126.6,126.2,125.6,123.5,121.0,120.6,120.2,119.5,41.7,40.1,35.2,34.4,31.8,31.8,31.3,27.7,24.5,22.2.

HRMS (ESI) calculated value (C)₁₀₀H₁₂₅N₂Pd[M-Cl]⁺)1455.8893, found 1456.8885.

Example 7: synthesis of Palladium Complex (R, R, R, R) - (DM-ANIPE) Pd (cin) Cl (Compound IV-5)

According to the general procedure A, compound V-5(102.0mg, 0.11mmol) was added to an 8mL vial and 95.1mg of a yellow solid was isolated (yield: 75%, compound IV-5).¹H NMR(400MHz,CDCl₃)δ:7.48(s,2H),7.33(d,J＝8.2Hz,4H),7.27–7.13(m,10H),7.00(s,1H),6.94–6.80(m,4H),6.28(s,4H),5.94(d,J＝6.9Hz,2H),5.77(s,2H),4.80(m,2H),4.56(m,1H),4.19(m,2H),2.51(m,6H),2.35(d,J＝3.6Hz,12H),2.19(s,3H),1.56(d,J＝7.3Hz,12H),1.39(s,12H).¹³C NMR(101MHz,CDCl₃)δ:188.6,145.1,144.7,143.2,140.5,139.2,137.9,137.5,137.0,133.9,129.1,128.3,128.3,128.2,128.0,127.8,127.2,126.7,126.7,126.1,125.7,125.5,125.4,125.3,120.1,109.7,93.9,44.4,41.6,38.7,29.8,25.3,24.2,22.3,21.8,21.6,21.6,20.4.

HRMS (MALDI) calculated value (C)₇₆H₇₇N₂Pd[M-Cl]+)1124.5164, found 1124.5275.

Example 8: synthesis of Palladium Complex (R, R, R, R) - (ANIPE) Pd (cin) Cl (Compound IV-6)

According to the general procedure A, compound V-6(100.0mg,0.12mmol) was added to an 8mL vial and 89.2mg of a yellow solid was isolated (yield: 71%, compound IV-6).¹H NMR(400MHz,CDCl₃)δ:7.77(d,J＝7.7Hz,2H),7.64(d,J＝7.4Hz,2H),7.58–7.40(m,7H),7.35(m,8H),7.00(s,1H),6.93(s,1H),6.86(t,J＝7.6Hz,2H),6.75–6.66(m,4H),6.30(m,6H),5.99(m,2H),5.05(m,2H),4.92–4.40(m,2H),4.39–4.23(m,2H),2.53(m,6H),1.59(m,12H),1.46(m,2H).¹³C NMR(101MHz,CDCl₃)δ:188.3,145.1,144.8,144.5,142.8,140.7,139.52,137.5,134.0,129.1,129.0,128.7,128.3,128.2,128.2,128.0,127.7,127.5,127.2,126.9,126.9,126.5,126.3,126.1,125.4,125.3,120.7,109.1,95.3,91.0,47.2,44.2,41.8,41.6,38.8,25.4,22.8,22.7,22.2.

HRMS (ESI) calculated value (C)₆₈H₆₁N₂Pd[M-Cl]+)1007.3885, found 1007.3842.

Example 9: synthesis of Palladium Complex (R, R, R, R) - (IPE) Pd (cin) Cl (Compound IV-7)

According to the general procedure A, compound V-7(100.0mg,0.12mmol) was added to an 8mL vial and 89.2mg of a yellow solid was isolated (yield: 71%, compound IV-7).¹H NMR(400MHz,CDCl₃)δ:7.80(d,J＝7.6Hz,2H),7.66(d,J＝7.4Hz,2H),7.56–7.30(m,13H),7.23(m,4H),7.20–7.13(m,2H),7.08–6.98(m,4H),6.85(m,2H),5.90(s,2H),5.04(m,1H),4.84(q,J＝7.3Hz,1H),4.74–4.46(m,2H),4.17(m,2H),2.58(t,J＝7.8Hz,1H),2.45(m,6H),1.70–1.54(m,12H),1.29(m,1H).¹³C NMR(101MHz,CDCl₃)δ:181.9,181.3,147.5,144.9,144.8,144.5,144.4,141.3,139.0,138.0,137.5,135.3,129.0,128.6,128.5,128.4,128.2,128.1,128.0,128.0,127.6,127.5,127.2,127.0,126.9,126.8,126.3,126.3,126.0,124.6,124.5,109.1,108.8,93.6,90.1,46.9,44.4,41.2,41.1,38.6,24.6,22.4,22.0,22.0.

HRMS (ESI) calculated value (C)₅₈H₅₇N₂Pd[M-Cl]⁺)883.3572, found 883.3539.

Example 10: single crystal diffraction experiments for Compounds IV-1 and IV-3

1. Single crystal cultivation: dissolving compound IV-1(30mg) or IV-3(20mg) in chloroform (3mL), filtering with a filter membrane, and standing the filtrate in wide-mouth bottles filled with n-hexane (15mL) respectively to obtain the single crystal.

2. The test parameters are shown in tables 1 and 2 above.

3. And (3) testing results: the configuration of compound IV-1 and compound IV-3 was determined by single crystal diffraction.

Example 11: reaction condition optimization

The reaction was carried out on a 0.1mmol scale; the yield was determined by NMR analysis with 1,3, 5-trimethylbenzene as internal standard; the ee value was determined by chiral HPLC on a chiral stationary phase.

Example 12: synthesis of axial chiral biaryl compound

General procedure A to a 15mL Schlenk flask equipped with a stir bar were added sequentially compound IV-1(2.8mg, 2. mu. mol), potassium hydroxide (22.4mg,0.40mmol), aryl bromide II (0.2mmol), arylboronic acid III (0.24mmol) and t-butanol (1.0mL, 0.2M). After replacement with a nitrogen atmosphere, the reaction mixture was stirred at 50 ℃ for 24 hours. Stopping the reaction, enabling the reaction solution to pass through a short silica gel column, diluting with ethyl acetate, concentrating an organic phase, and purifying by column chromatography to obtain a target product, wherein the ee value is measured by chiral HPLC, and the configuration of the compound is measured by a single crystal diffraction experiment.

Example 13

General procedure B to a 15mL Schlenk flask equipped with a stir bar were added sequentially compound IV-1(2.8mg, 4. mu. mol), cesium carbonate (162.9mg,0.50mmol), aryl bromide II (0.2mmol), arylboronic acid III (0.40mmol) and tert-butanol/water (9:1,1.0mL, 0.2M). After replacement with a nitrogen atmosphere, the reaction mixture was stirred at 60 ℃ for 24 hours. Stopping the reaction, enabling the reaction solution to pass through a short silica gel column, diluting with ethyl acetate, concentrating an organic phase, and purifying by column chromatography to obtain a target product, wherein the ee value is measured by chiral HPLC, and the configuration of the compound is measured by a single crystal diffraction experiment.

Example 14

General procedure C to a 15mL Schlenk flask equipped with a stirrer were added sequentially compound IV-1(1.4mg, 1. mu. mol), potassium tert-butoxide (29.2mg,0.26mmol), aryl bromide II (0.2mmol), aryl boronic acid III (0.26mmol) and toluene/water (9:1,0.8mL, 0.25M). After replacement with a nitrogen atmosphere, the reaction mixture was stirred at 30 ℃ for 24 hours. Stopping the reaction, enabling the reaction solution to pass through a short silica gel column, diluting with ethyl acetate, concentrating an organic phase, and purifying by column chromatography to obtain a target product, wherein the ee value is measured by chiral HPLC, and the configuration of the compound is measured by a single crystal diffraction experiment.

Example 15

Compound I-1 was prepared according to general procedure A as a white solid in 91% yield.¹H NMR(400MHz,CDCl₃)δ:8.03–7.88(m,3H),7.83(d,J＝8.2Hz,1H),7.58(m,1H),7.47–7.35(m,3H),7.34–7.20(m,3H),7.20–7.11(m,2H),3.70(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.7,134.7,134.4,133.8,133.0,129.6,129.1,128.6,128.3,127.9,127.9,126.5,126.3,126.0,125.8,125.7,125.6,123.7,123.3,113.9,56.8.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1mL/min,230nm) gave 97% ee: t_R(major)＝5.9min,t_R(minor)＝7.0min.

Compound I-2 was prepared according to general procedure A as a white solid with a yield of 98%.¹H NMR(400MHz,CDCl₃)δ:7.91(d,J＝8.2Hz,2H),7.84(m,2H),7.56(m,1H),7.47–7.39(m,2H),7.38–7.31(m,2H),7.22(d,J＝4.0Hz,2H),7.19–7.11(m,2H),2.09(s,3H).¹³C NMR(101MHz,CDCl₃)δ:137.6,136.2,134.5,133.8,133.6,132.7,132.1,128.7,128.4,127.9,127.7,127.7,126.4,126.3,126.1,126.1,126.0,126.0,125.8,124.9,20.7.

HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 95% ee: t_R(mior)＝6.8min,t_R(major)＝9.3min.

Compound I-3 was prepared as a colorless oil in 92% yield according to general procedure A.¹H NMR(400MHz,CDCl₃)δ:8.14–7.95(m,3H),7.93(d,J＝8.2Hz,1H),7.69(t,J＝7.6Hz,1H),7.60–7.44(m,4H),7.44–7.27(m,4H),7.25–7.17(m,3H),7.03(m,2H),5.11(q,J＝12.6Hz,2H).¹³C NMR(101MHz,CDCl₃)δ:153.7,137.3,134.6,134.4,133.8,133.1,129.5,129.4,128.6,128.6,128.3,127.9,127.9,127.6,126.9,126.5,126.4,126.0,125.8,125.8,125.7,124.7,124.0,116.1,71.4.

HPLC analysis (AD-H, 1% IPA in cyclohexaneSolution, 1.0mL/min,254nm) was determined to be 90% ee: t_R(major)＝6.1min,t_R(minor) ═ 9.4min.HRMS (ESI) calculated value C₂₇H₂₄NO[M+H]⁺m/z 378.1852, found 378.1856.

Compound I-4 was prepared according to general procedure C as a white solid in 85% yield.¹H NMR(400MHz,CDCl₃)δ:7.92(m,3H),7.85(d,J＝8.2Hz,1H),7.63–7.54(m,2H),7.43(m,2H),7.38–7.29(m,2H),7.28–7.14(m,3H),5.06(s,2H),3.44–3.25(m,2H),1.00(t,J＝7.1Hz,3H).¹³C NMR(101MHz,CDCl₃)δ:152.4,134.7,134.4,133.7,133.1,129.8,129.5,128.5,128.3,127.9,127.8,126.2,126.4,126.0,125.8,125.6,125.0,124.14117.2,93.9,64.2,15.1.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 92% ee: t_R(major)＝7.8min,t_R(minor) ═ 9.9min.HRMS (ESI) calculated value C₂₃H₂₄NO₂[M+H]⁺m/z 346.1802, found 346.1798.

Single Crystal diffraction experiment of Compound I-4

1. Single crystal cultivation: t isolated in the above example_RCompound I-4(20mg) at 7.8min (major) was dissolved in chloroform (1mL), filtered through a filter membrane, the filtrate was placed in a nuclear magnetic tube and left to stand, and the solvent was slowly evaporated to obtain the single crystal.

2. The test parameters are shown in table 3 below:

TABLE 3 Single Crystal data for Compound I-4

3. And (3) testing results: the configuration of the compound I-4 is determined by single crystal diffraction, and thus the configurations of the compounds I-1 to I-3 and I-5 to I-40 are also possible.

Compound I-6 was prepared as a colorless oil in 85% yield according to general procedure C.¹H NMR(400MHz,CDCl₃)δ:7.97(dd,J＝12.4,8.3Hz,2H),7.81(d,J＝8.8Hz,1H),7.75(d,J＝8.8Hz,1H),7.66–7.57(m,1H),7.57–7.46(m,2H),7.42(d,J＝8.4Hz,1H),7.39–7.32(m,1H),7.18(d,J＝8.8Hz,1H),6.95–6.82(m,1H),6.35(d,J＝2.5Hz,1H),4.96(s,1H),4.88(s,1H).¹³C NMR(101MHz,CDCl₃)δ:154.3,151.7,135.4,134.3,132.8,131.6,130.1,129.8,129.3,128.6,127.0,126.7,126.2,125.9,124.5,117.6,115.1,115.1,115.1,107.4,107.3.

HPLC analysis (OD-H, 15% IPA in cyclohexane, 1.0mL/min,220nm) gave 99% ee: t_R(minor)＝9.7min,t_R(major) ═ 12.4min HRMS (ESI) calcd for C₂₀H₁₅O₂[M+H]⁺m/z 287.1067, found 287.1069.

Compound I-7 was prepared as a colorless oil in 96% yield according to general procedure C.¹H NMR(400MHz,CDCl₃)δ:7.72(m,2H),7.45–7.30(m,3H),7.25(m,1H),7.11(d,J＝8.8Hz,1H),6.91(m,1H),6.47(d,J＝2.5Hz,1H),5.19(s,1H),5.04(s,1H),2.03(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.3,150.7,139.1,134.6,133.3,131.7,131.1,130.2,129.4,129.0,127.0,124.5,119.1,115.0,106.8,19.6.

HPLC analysis (AD-H, 10% IPA in cyclohexane, 1.0mL/min,254nm) gave 92% ee: t_R(minor)＝15.9min,t_R(minor) ═ 21.0min HRMS (ESI) calculated value C₁₇H₁₅O₂[M+H]⁺m/z 251.1067, found 251.1070.

Compound I-8 was prepared as a colorless oil in 98% yield according to general procedure C.¹H NMR(400MHz,CDCl₃)δ:8.69(m,1H),8.05(m,3H),7.87(m,1H),7.70(m,1H),7.59(m,2H),7.48(d,J＝8.9Hz,1H),7.45–7.36(m,2H),7.20(d,J＝8.9Hz,1H),5.48(s,1H),3.99(s,3H).¹³C NMR(101MHz,CDCl₃)δ:167.4,153.3,136.5,134.3,132.8,131.5,131.3,130.9,129.7,129.5,128.6,128.0,127.1,126.7,126.1,126.1,125.6,125.2,125.0,119.1,118.5,52.2.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 90% ee: t_R(major)＝14.9min,t_RCalculated value C (minor) ═ 16.2min hrms (ESI)₂₂H₁₅O₃[M-H]^-m/z 327.1027, found 327.1023.

Compound I-9 was prepared as a colorless oil in 86% yield according to general procedure C.¹H NMR(400MHz,CDCl₃)δ:7.99(d,J＝8.4Hz,1H),7.93(m,3H),7.71–7.39(m,5H),7.30(m,2H),7.25(m,2H),3.66(m,1H),3.46–3.05(m,1H),2.99–2.15(m,2H),0.68m,3H),0.50–0.24(m,3H).¹³C NMR(101MHz,CDCl₃)δ:169.9,135.6,134.2,133.9,133.3,132.9,132.7,132.1,129.6,128.6,128.5,128.3,128.1,127.8,127.6,127.3,127.1,126.8,126.7 126.3,126.2,126.1,125.7,125.6,125.4,124.4,123.5,123.2,42.7,42.5,37.5,14.0,13.6,11.5.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 93% ee: t_R(major)＝14.9min,t_RCalculated value C (minor) ═ 16.9min hrms (ESI)₂₅H₂₄NO[M+H]⁺m/z 354.1852, found 354.1849.

Compound I-10 was prepared according to general procedure B as a brown oil in 81% yield.¹H NMR(400MHz,CDCl₃)δ:9.51(s,1H),8.13(m,1H),7.88–7.81(m,2H),7.71(m,1H),7.57(m,1H),7.41(m,2H),7.35–7.27(m,2H),7.22–7.16(m,1H),2.17(s,3H).¹³C NMR(101MHz,CDCl₃)δ:192.2,143.9,134.8,134.3,133.4,133.4,131.9,131.6,128.5,128.4,128.3,128.1,127.4,126.6,125.8,125.3,21.0.

HPLC analysis (OD-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 90% ee: t_R(major)＝8.9min,t_R(minor)＝9.5min.

Compound I-11 was prepared according to general procedure B as a yellow oil in 75% yield.¹H NMR(400MHz,CDCl₃)δ:7.84(m,2H),7.49–7.41(m,3H),7.40–7.34(m,1H),7.30–7.25(m,1H),7.05(m,1H),6.93–6.85(m,2H),3.37(s,2H),2.29(s,3H).¹³C NMR(101MHz,CDCl₃)δ:144.4,134.8,134.4,132.7,132.4,131.0,129.0,128.7,128.0,127.8,126.3,125.8,125.2,124.8,118.7,115.4,20.4.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 85% ee: t_R(major)＝11.9min,t_R(minor) ═ 15.7min.HRMS (ESI) calculated C₁₇H₁₆N[M+H]⁺m/z 234.1277, found 234.1278.

Compound I-12 was prepared according to general procedure B as a brown oil in 81% yield.¹H NMR(400MHz,CDCl₃)δ:7.92(d,J＝9.0Hz,1H),7.90–7.81(m,2H),7.65(m,1H),7.56(m,1H),7.40–7.31(m,4H),7.20–7.12(m,1H),4.24–4.00(m,2H),1.23(t,J＝7.0Hz,3H).¹³C NMR(101MHz,CDCl₃)δ:153.5,136.1,136.0,133.9,132.9,131.5,130.3(q,J＝30.0Hz),129.7,128.6,127.8,127.5,126.75,126.3,126.2(q,J＝5.1Hz),125.2,124.1(q,J＝275.2Hz),123.5,114.2,64.6,14.9.¹⁹F NMR(376MHz,CDCl₃)δ:-60.8.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 91% ee: t_R(major)＝4.5min,t_RHrms (EI) calculated value C (minor) ═ 6.4min₁₉H₁₅OF₃[M]⁺m/z 316.1075, found 316.1067.

Compound I-13 was prepared according to general procedure A as a white solid in 89% yield.¹H NMR(400MHz,CDCl₃)δ:8.20(dd,J＝8.4,1.1Hz,1H),7.85(m,2H),7.53–7.42(m,2H),7.39–7.33(m,1H),7.30–7.22(m,3H),7.19(m,2H),7.15–7.08(m,1H),2.07(s,3H).¹³C NMR(101MHz,CDCl₃)δ:158.4(d,J＝252.5Hz),135.4,133.9(d,J＝4.7Hz),133.7,133.5(d,J＝4.7Hz),132.1,128.7,127.9(d,J＝5.3Hz),127.5(d,J＝8.0Hz),127.2,126.3(d,J＝2.0Hz),126.2,126.1,126.1,125.0,124.0(d,J＝16.4Hz),120.9(d,J＝5.3Hz),109.5,109.3,20.7.¹⁹F NMR(376MHz,CDCl₃)δ:-60.8.

HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 92% ee: t_R(minor)＝16.4min,t_RCalculated value C of (major) ═ 25.9min hrms (EI)₂₁H₁₅OF[M]⁺m/z 286.1158, found 286.1159.

Compound I-14 was prepared according to general procedure A as a yellow solid in 90% yield.¹H NMR(400MHz,CDCl₃)δ:8.65(d,J＝8.8Hz,1H),8.18(m,1H),8.05(d,J＝9.1Hz,1H),7.92(d,J＝8.2Hz,1H),7.86(m,1H),7.68(m,1H),7.59(m,1H),7.48(d,J＝9.1Hz,1H),7.37(m,1H),7.35–7.27(m,2H),7.11(d,J＝8.5Hz,1H),3.79(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.6,147.3,135.7,134.1,134.0132.8,130.3,130.1,129.1,129.0,128.1,126.9,125.6,125.0,124.1,123.9,123.8,122.6,121.8,113.4,56.6.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 97% ee: t_R(major)＝10.0min,t_RCalculation of (minor) ═ 12.0min HRMS (EI) C₂₁H₁₅NO₃[M]⁺m/z 329.1052, found 329.1045.

Compound I-15 was prepared as a colorless oil in 95% yield according to general procedure A.¹H NMR(400MHz,CDCl₃)δ:8.40(m,1H),8.07(d,J＝7.3Hz,1H),7.93(m,2H),7.70(m,1H),7.52(d,J＝8.5Hz,1H),7.48–7.43(m,2H),7.43–7.39(m,1H),7.35(d,J＝8.4Hz,1H),7.29–7.24(m,1H),7.05(d,J＝8.5Hz,1H),2.11(s,3H).¹³C NMR(101MHz,CDCl₃)δ:143.9,134.4,134.2,132.8,132.8,132.5,132.5,132.0,128.7,128.7,128.5,128.1,127.9,127.1,126.9,126.5,125.7,125.7,125.3,118.1,109.9,20.6.

HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 95% ee: t_R(minor)＝16.4min,t_RCalculated value C of (major) ═ 25.9min hrms (EI)₂₂H₁₅N[M]⁺m/z 293.1204, found 293.1214.

Compound I-16 was prepared as a colorless oil in 99% yield according to general procedure C.¹H NMR(400MHz,CDCl₃)δ:8.49(d,J＝1.8Hz,1H),8.04(d,J＝9.0Hz,1H),7.88(dd,J＝8.9,1.8Hz,1H),7.45(d,J＝9.0Hz,1H),7.40–7.36(m,2H),7.34(m,2H),7.18(m,1H),3.89(s,3H),2.70(s,3H),2.00(s,3H).¹³C NMR(101MHz,CDCl₃)δ:197.9,155.9,137.6,135.9,135.5,132.4,131.1,130.8,130.6,130.0,127.9,127.8,125.8,125.5,124.6,124.5,114.0,56.4,26.7,19.8.

HPLC analysis (OD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 95% ee: t_R(minor)＝7.7min,t_RCalculated value C (major) ═ 8.3min. hrms (ESI)₂₀H₁₉O₂[M+H]⁺m/z 290.1380, found 291.1379.

Compound I-17 was prepared according to general procedure A using 1-naphthyl-trifluoromethanesulfonate (55.2mg,0.2mmol,1.0equiv) and 2-methoxy-1-naphthaleneboronic acid (48.5mg,0.24mmol,1.2equiv) as a colorless oil in 97% yield.¹H NMR(400MHz,CDCl₃)δ:8.03–7.92(m,3H),7.88(m,1H),7.63(m,1H),7.50–7.42(m,3H),7.34(m,2H),7.31–7.26(m,1H),7.23(dd,J＝6.6,1.4Hz,1H),7.17(m,1H),3.77(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.6,134.6,134.3,133.7,133.0,129.5,129.0,128.5,128.2,127.8,127.8,126.4,126.2,125.9,125.7,125.6,125.5,123.6,123.3,113.9,56.8.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1)0mL/min,220nm) 96% ee, tr (major) 6.2min, tr (minor) 7.6min.

Compound I-18:

prepared according to general procedure A using 1-bromo-2-methoxynaphthalene (47.4mg,0.2mmol,1.0equiv) and 2-methylphenylboronic acid (32.6mg,0.24mmol,1.2equiv) with 0.5 mol% catalyst as a colorless oil in 97% yield. 1H NMR (400MHz, CDCl)₃)δ:7.94(d,J＝9.0Hz,1H),7.91–7.84(m,1H),7.44–7.30(m,7H),7.26–7.22(m,1H),3.88(s,3H),2.06(s,3H).¹³C NMR(101MHz,CDCl₃)δ:153.8,137.7,136.2,133.6,131.0,129.9,129.1,129.1,128.0,127.6,126.5,125.7,125.2,124.6,123.6,113.7,56.7,56.7,19.9.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 93% ee: t_R(major)＝4.3min,t_R(minor)＝5.0min.

Compound I-18:

prepared according to general procedure A using 1-bromo-2-methoxynaphthalene (47.4mg,0.2mmol,1.0equiv) and 4,4,5, 5-tetramethyl-2- (2-methylphenyl) -1,3, 2-dioxaborolan (52.3mg,0.24mmol,1.2equiv) and 0.5 mol% catalyst as a colorless oil in 99% yield and 94% ee.

Compound I-18:

prepared according to general procedure A using 1-bromo-2-methoxynaphthalene (47.4mg,0.2mmol,1.0equiv) and 5, 5-dimethyl-2- (2-methylphenyl) -1,3, 2-dioxaborolan (49.0mg,0.24mmol,1.2equiv) and 0.5 mol% catalyst as a colorless oil in 91% yield 93% ee.

Compound I-18:

prepared according to general method B using 1-bromo-2-methoxynaphthalene (47.4mg,0.2mmol,1.0equiv) and potassium (2-methylphenyl) trifluoroborate (79.2mg,0.4mmol,2.0equiv) as a colorless oil in 98% yield and 90% ee.

Compound I-19 was prepared according to general procedure A using 4,4,5, 5-tetramethyl-2- (2-methyl-1-naphthyl) -1,3, 2-dioxaborolan (53.6mg,0.2mmol,1.0equiv), 1-bromoisoquinoline (83.2mg,0.4mmol,2.0equiv) and 2 mol% catalyst to give a colorless oil in 60% yield.¹H NMR(400MHz,CDCl₃)δ:8.73(d,J＝5.7Hz,1H),8.01–7.82(m,3H),7.75(d,J＝5.8Hz,1H),7.66(m,1H),7.47(d,J＝8.4Hz,1H),7.43–7.33(m,3H),7.25–7.19(m,1H),6.99(d,J＝8.5Hz,1H),2.10(s,3H).¹³C NMR(101MHz,CDCl₃)δ:160.6,142.9,136.4,134.9,134.4,133.0,132.1,130.4,128.7,128.5,128.4,128.0,127.5,127.3,127.1,126.3,125.7,125.0,120.1,20.2.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 90% ee: t_R(major)＝10.3min,t_R(minor) ═ 10.9min.HRMS (ESI) calculated C₂₀H₁₆N[M+H]⁺m/z 270.1277, found 270.1283.

Compound I-21 was prepared according to general procedure A as a colorless oil in 88% yield.¹H NMR(400MHz,CDCl₃)δ:9.06(d,J＝4.4Hz,1H),8.27(d,J＝8.5Hz,1H),7.90(m,2H),7.72(m,1H),7.49(d,J＝8.5Hz,1H),7.41(t,J＝7.6Hz,1H),7.37–7.30(m,2H),7.30–7.21(m,3H),7.08(d,J＝8.5Hz,1H),2.11(s,3H).¹³C NMR(101MHz,CDCl₃)δ:150.3,148.5,147.1,133.9,133.2,132.5,131.9,129.8,129.7,128.6,128.4,128.0,128.0,127.0,126.5,126.0,125.7,125.2,122.8,20.5.

HPLC analysis (AD-H, 3% IPA in cyclohexane, 1.0mL/min,254nm) gave 93% ee: t_R(minor)＝11.9min,t_RCalculated value C (major) ═ 18.2min hrms (ESI)₂₀H₁₆N[M+H]⁺m/z 270.1277, found 270.1279.

Compound I-22:

prepared according to general procedure a as yellow oil in 94% yield.¹H NMR(400MHz,CDCl₃)δ:8.92(m,1H),8.25(d,J＝8.5Hz,1H),7.90(d,J＝8.3Hz,2H),7.85(m,1H),7.58–7.53(m,1H),7.52–7.44(m,2H),7.44–7.38(m,1H),7.23(m,1H),7.18(m,1H),7.10(d,J＝8.5Hz,1H),2.10(s,3H).¹³C NMR(101MHz,CDCl₃)δ:150.5,148.6,137.9,134.6,134.6,134.3,133.4,132.0,129.3,129.1,128.6,128.6,128.4,128.1,128.0,127.8,126.2,126.0,125.1,121.3,20.6.

HPLC analysis (AD-H, 3% IPA in cyclohexane, 1.0mL/min,254nm) gave 94% ee: t_R(minor)＝10.2min,t_RCalculated value C (major) ═ 11.1min hrms (ESI)₂₀H₁₆N[M+H]⁺m/z 270.1277, found 270.1276.

Compound I-22:

prepared according to general procedure A as yellow oil in 87% yield with 94% ee.

Compound I-23 was prepared according to general procedure A as a colorless oil in 91% yield.¹H NMR(400MHz,CDCl₃)δ:9.36(s,1H),8.35(d,J＝5.9Hz,1H),8.08(d,J＝8.2Hz,1H),8.02(d,J＝9.0Hz,1H),7.89(d,J＝8.2Hz,1H),7.76(t,J＝7.6Hz,1H),7.67(d,J＝7.0Hz,1H),7.45(d,J＝9.1Hz,1H),7.35(t,J＝7.5Hz,1H),7.31–7.21(m,1H),7.13(m,2H),3.77(s,3H).¹³C NMR(101MHz,CDCl₃)154.7,152.9,143.2,135.7,134.0,133.9,132.9,130.2,129.1,129.0,128.1,127.4,127.1,126.8,125.0,123.8,121.2,119.0 113.5 56.6.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 95% ee: t_R(major)＝17.8min,t_R(minor) ═ 19.6min.HRMS (ESI) calculated value C₂₀H₁₆NO[M+H]⁺m/z 286.1226, found 286.1227.

Compound I-24 was prepared according to general procedure A as a colorless oil in 84% yield.¹H NMR(400MHz,CDCl₃)δ:8.70(s,1H),8.57(d,J＝5.7Hz,1H),8.04–7.89(m,3H),7.85(t,J＝7.7Hz,1H),7.78(d,J＝5.8Hz,1H),7.53(t,J＝7.7Hz,2H),7.44(t,J＝7.5Hz,1H),7.31–7.26(m,1H),7.13(d,J＝8.5Hz,1H),2.16(s,3H).¹³C NMR(101MHz,CDCl₃)δ:151.2,143.1,138.6,136.3,134.6,133.9,133.5,132.0,130.4,129.4,128.6,128.3,128.0,127.7,126.3,126.3 125.9,125.1,120.8,20.7.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 94% ee: t_R(minor)＝8.8min,t_RCalculated value C (major) ═ 10.0min hrms (ESI)₂₀H₁₆N[M+H]⁺m/z 270.1277, found 270.1278.

Compound I-25 was prepared according to general procedure A as a colorless oil in 82% yield.¹H NMR(400MHz,CDCl₃)δ:8.86(m,1H),8.27(m,1H),7.97(m,1H),7.92(d,J＝8.3Hz,2H),7.71(t,J＝7.5Hz,1H),7.66(m,1H),7.55(d,J＝8.4Hz,1H),7.45–7.36(m,2H),7.30–7.23(m,1H),7.20(d,J＝8.5Hz,1H),2.18(s,3H).¹³C NMR(101MHz,CDCl₃)δ:150.6,147.2,139.3,136.4,135.9,134.2,133.5,132.1,131.7,128.7,128.7,128.0,127.8,127.7,126.4,126.2,125.7,124.6,121.1,20.9.

HPLC analysis (IC, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 90% ee: t_R(major)＝11.4min,t_RCalculated value C (minor) ═ 12.0min hrms (ESI)₂₀H₁₆ON[M+H]⁺m/z 270.1277, found 270.1279.

Compound I-26 was prepared as a colorless oil in 92% yield according to general procedure A. H NMR (400MHz, CDCl)₃)δ:8.77(m,1H),8.29(d,J＝9.3Hz,1H),7.96(t,J＝7.7Hz,2H),7.70–7.58(m,2H),7.54–7.45(m,2H),7.42(m,1H),7.34–7.27(m,2H),7.16–7.05(m,1H),3.78(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.7,148.1,143.7,133.8,133.7,133.2,132.8,130.7,129.3,128.6,128.4,128.2,126.1,125.9,125.5,122.9,121.3,116.8,56.7,56.7.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 96% ee: t_R(minor)＝13.1min,t_RCalculated value C (major) ═ 14.4min hrms (ESI)₂₀H₁₆NO[M+H]⁺m/z 286.1226, found 286.1226.

Compound I-27 was prepared as a colorless oil in 98% yield according to general procedure A.¹H NMR(400MHz,CDCl₃)δ:8.92(m,1H),8.25(d,J＝8.5Hz,1H),8.00(d,J＝9.1Hz,1H),7.95–7.82(m,2H),7.68(m,1H),7.56–7.49(m,1H),7.44(d,J＝9.1Hz,1H),7.38–7.28(m,1H),7.27–7.22(m,2H),7.22–7.10(m,2H),3.75(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.6,150.2,148.4,135.0,134.7,134.2,130.0,129.3,129.1,129.0,129.0,128.2,128.0,126.7,125.1,123.8,121.4,121.1,113.4,56.6,56.5.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 95% ee: t_R(minor)＝14.0min,t_RCalculated value C (major) ═ 15.0min hrms (ESI)₂₀H₁₆NO[M+H]⁺m/z 286.1226, found 286.1230.

Compound I-28 was prepared according to general procedure A as a yellow oil in 79% yield.¹H NMR(400MHz,CDCl₃)δ:8.96–8.84(m,1H),8.21(d,J＝8.5Hz,1H),7.95(d,J＝9.0Hz,1H),7.90–7.79(m,2H),7.68(m,1H),7.50(d,J＝7.0Hz,1H),7.39(d,J＝9.0Hz,1H),7.32(t,J＝7.4Hz,1H),7.26–7.21(m,1H),7.19(m,1H),7.15(d,J＝8.5Hz,1H),4.01(m,2H),1.02(t,J＝7.0Hz,3H).¹³C NMR(101MHz,CDCl₃)δ:154.0,150.2,148.5,135.2,134.8,134.3,129.9,129.2,129.1,128.9,128.2,128.0,126.7,125.2,123.8,122.3,120.9,115.2,65.1,14.9.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 92% ee: t_R(major)＝11.1min,t_R(minor) ═ 13.5min HRMS (ESI) calculated C₂₁H₁₈NO[M+H]⁺m/z 300.1383, found 300.1383.

Compound I-29 was prepared according to general procedure A as a yellow oil in 94% yield.¹H NMR(400MHz,CDCl₃)δ:8.59(m,1H),7.91(d,J＝9.0Hz,1H),7.83(m,1H),7.49(m,1H),7.38–7.29(m,3H),7.23(m,2H),3.82(s,3H),2.25(s,3H).¹³C NMR(101MHz,CDCl₃)δ:158.0,153.8,148.2,138.9,133.0,131.4,129.8,128.9,128.1,126.8,124.4,123.7,121.9,120.9,113.2,56.4,56.3,22.7.

HPLC analysis (OJ-H, 5% IPA in cyclohexane, 1.0mL/min,254nm) gave 93% ee: t_R(minor)＝9.8min,t_RCalculated value C (major) ═ 16.0min.hrms (ESI)₁₇H₁₆NO[M+H]⁺m/z 250.1226, found 250.1226.

Compound I-30 was prepared according to general procedure A as a yellow oil in 79% yield.¹H NMR(400MHz,CDCl₃)δ:9.35(s,1H),8.79(s,1H),8.17(m,1H),8.06(m,1H),7.94–7.88(m,2H),7.56(m 1H),7.50(d,J＝8.4Hz,1H),7.42(m,1H),7.26(m,1H),7.04(m,1H),2.11(s,3H).¹³C NMR(101MHz,CDCl₃)δ:159.2,155.5,150.5,138.7,134.8,134.1,133.4,132.4,132.0,129.8,128.7,128.6,128.1,128.0,126.6,125.6,125.3,124.5,20.8.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 94% ee: t_R(minor)＝9.8min,t_RCalculated value C (major) ═ 11.3min hrms (ESI)₁₉H₁₅N₂[M+H]⁺m/z 271.1230, found 271.1233.

Compound I-31 was prepared according to general procedure A as a white solid in 93% yield.¹H NMR(400MHz,CDCl₃)δ:8.07(d,J＝9.0Hz,1H),7.95(d,J＝8.2Hz,1H),7.69(t,J＝7.7Hz,1H),7.53(d,J＝8.7Hz,2H),7.43–7.32(m,4H),7.30–7.22(m,2H),6.84(m,1H),6.76(d,J＝7.9Hz,1H),3.90(s,3H),3.78(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.3,141.3,141.1,133.7,131.3,129.5,129.2,127.9,126.5,125.6,125.4,125.3,123.9,123.7,122.8,122.0,121.8,121.8,118.7,114.0,108.1,107.6,56.9,29.2.

HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 99% ee: t_R(minor)＝8.4min,t_RCalculated value C (major) ═ 9.9min hrms (ESI)₂₄H₂₀NO[M+H]⁺m/z 338.1539, found 338.1542.

Compound I-32 was prepared according to general procedure A as a white solid in 82% yield.¹H NMR(400MHz,CDCl₃)δ:7.90(d,J＝9.0Hz,1H),7.84–7.78(m,1H),7.37(d,J＝9.0Hz,1H),7.35–7.26(m,3H),7.25–7.19(m,2H),6.96(m,1H),6.71(d,J＝1.3Hz,1H),3.79(s,3H),3.74(s,3H),1.40(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.5,137.5,134.9,129.4,129.0,128.7,127.7,127.4,127.3,126.2,126.0,124.8,123.4,121.4,121.4,113.7,111.0,108.5,56.9,32.7,10.6.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,230nm) gave 90% ee: t_R(major)＝8.8min,t_RCalculated value C (minor) ═ 12.1min hrms (ESI)₂₁H₂₀NO[M+H]⁺m/z 302.1539, found 302.1546.

Compound I-33 preparation according to general procedure AA colorless oil was obtained in 97% yield.¹H NMR(400MHz,CDCl₃)δ:8.01(m,1H),7.90(t,J＝8.8Hz,2H),7.52(t,J＝7.7Hz,2H),7.44(m,1H),7.37–7.28(m,4H),6.73(m,1H),2.21(s,3H).¹³C NMR(101MHz,CDCl₃)δ:140.0,139.6,136.4,135.2,133.9,133.0,132.1,128.7,127.9,127.7,126.3,126.2,126.1,126.0,125.0,124.4,123.6,121.7,20.7.

HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 86% ee: t_R(minor)＝8.4min,t_RCalculated value C of (major) ═ 11.7min hrms (EI)₁₅H₁₄S[M]⁺m/z 274.0816, found 274.0820.

Compound I-34 was prepared according to general procedure B as a white solid with a yield of 98%.¹H NMR(400MHz,CDCl₃)δ:8.88(m,1H),8.75(m,1H),8.25(d,J＝9.3Hz,1H),8.20(d,J＝8.5Hz,1H),7.81(m,1H),7.63(d,J＝9.4Hz,1H),7.59(m),7.45(m,2H),7.19(dd,J＝8.5,4.2Hz,1H),7.12(dd,J＝8.6,4.1Hz,1H),3.75(s,3H).¹³C NMR(101MHz,CDCl₃)δ:154.7,150.4,148.5,148.4,143.9,134.3,133.6,133.3,131.3,129.6,129.2,129.2,129.1,128.0,121.6,121.2,121.2,116.5,56.6.

HPLC analysis (AD-H, 10% IPA in cyclohexane, 1.0mL/min,230nm) gave 95% ee: t_R(minor)＝19.9min,t_RCalculated value C (major) ═ 26.3min hrms (ESI)₁₉H₁₅N₂O[M+H]⁺m/z 287.1179, found 287.1182.

Compound I-35 was prepared according to general procedure A as a white solid in 57% yield.¹H NMR(400MHz,CDCl₃)δ:7.97(d,J＝9.0Hz,2H),7.86(d,J＝8.1Hz,2H),7.45(d,J＝9.0Hz,2H),7.31(t,J＝7.4Hz,2H),7.24–7.16(m,2H),7.10(d,J＝8.5Hz,2H),3.76(s,6H).¹³C NMR(101MHz,CDCl₃)δ:155.1,134.2,129.5,129.4,128.1,126.4,125.4,123.6,119.7,114.4,57.1.

HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,280nm) gave 96% ee: t_R(major)＝8.3min,t_R(minor)＝9.5min.

Compound I-36 was prepared according to general procedure A as a white solid in 62% yield.¹H NMR(400MHz,CDCl₃)δ:7.91(d,J＝9.0Hz,1H),7.86–7.75(m,3H),7.36(dd,J＝14.9,9.0Hz,2H),7.28–7.21(m,2H),7.19–7.09(m,3H),7.07(m,4H),6.95–6.84(m,2H),5.04–4.89(m,2H),3.67(s,3H).¹³C NMR(101MHz,CDCl₃)δ:155.1,154.2,137.7,134.3,134.2,129.6,129.5,129.4,129.3,128.3,128.1,128.0,127.4,126.9,126.5,126.4,125.6,125.5,123.9,123.6,121.0,119.6,116.4,114.0,56.8.

HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,254nm) gave 92% ee: t_R(major)＝7.0min,t_R(minor)＝9.1min.

Compound I-37 was prepared according to general procedure A as a white solid in 85% yield.¹H NMR(400MHz,CDCl₃)δ:7.90(d,J＝9.0Hz,1H),7.86–7.78(m,1H),7.30(m,5H),7.14(d,J＝7.6Hz,1H),7.03(t,J＝8.6Hz,1H),3.83(s,3H),1.97(s,3H).¹³C NMR(101MHz,CDCl₃)δ:161.9,159.5,154.4,140.5,140.5,133.2,129.9,129.1,128.8,128.8,128.8,128.2,128.2,126.8,125.4,125.4,124.4,123.7,123.7,123.6,117.6,113.7,113.6,112.9,112.7,56.7,56.7,19.8,19.6.¹⁹F NMR(376MHz,CDCl₃)δ:-113.9.

HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220nm) gave 95% ee: t_R(major)＝5.0min,t_R(minor) ═ 6.5min HRMS (EI) calculated C₁₈H₁₅OF[M]⁺m/z 266.1107, found 226.1102.

Compound I-38 was prepared according to general procedure A in 54% yield as a brown solid.¹H NMR(400MHz,CDCl₃)8.77(m,1H),8.25(d,J＝9.3Hz,1H),7.99(d,J＝9.0Hz,1H),7.88(d,J＝8.2Hz,1H),7.68(d,J＝9.3Hz,1H),7.45(d,J＝9.0Hz,2H),7.33(m,1H),7.27–7.21(m,1H),7.13(m,1H),7.10–7.05(m,1H),3.79(s,3H),3.77(s,3H).¹³C NMR(101MHz,CDCl₃)δ:155.2,155.1,148.3,144.3,134.0,133.7,130.8,130.0,129.3,129.2,128.2,126.7,125.0,123.8,121.4,119.4,118.2,117.4,114.1,56.9,56.9.

HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,280nm) gave 94% ee: t_R(major)＝22.5min,t_R(minor)＝27.5min.HRMS(ESI)calculated

Compound I-39 was prepared according to general procedure A using 1, 4-dibromonaphthalene (57.2mg,0.2mmol,1.0equiv), (2-methoxy-1-naphthyl) boronic acid (145.5mg,0.72mmol,3.6equiv), potassium hydroxide (56mg,1.0mmol,5.0equiv), 2 mol% catalyst and 2mL t-butanol to give a white solid in 74% yield.¹H NMR(400MHz,CDCl₃)δ:7.98(d,J＝9.0Hz,2H),7.87(d,J＝8.1Hz,2H),7.56(s,2H),7.47(d,J＝9.0Hz,2H),7.42(m,2H),7.37–7.32(m,3H),7.32–7.19(m,5H),3.82(s,6H).¹³C NMR(101MHz,CDCl₃)δ:154.9,134.5,134.3,133.3,129.6,129.2,128.3,127.9,126.6,126.5,126.0,125.7,123.7,123.7,114.1,57.0.

HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,220nm)>99％ee:t_R(minor)＝8.0min,t_RCalculated value C (major) ═ 16.0min.hrms (ESI)₃₂H₂₅O₂[M+H]⁺m/z 441.1849, found 441.1857.

Compound I-40 was prepared according to general procedure A using 1, 4-dibromonaphthalene (57.2mg,0.2mmol,1.0equiv), (2-methyl-1-naphthyl) boronic acid (133.9mg,0.72mmol,3.6equiv), potassium hydroxide (56mg,1.0mmol,5.0equiv), 2 mol% catalyst and 2mL t-butanol to give a white solid in 60% yield.¹H NMR(400MHz,CDCl₃)δ:7.95(d,J＝8.3Hz,5H),7.59(d,J＝8.2Hz,2H),7.54(s,2H),7.46(m,3H),7.39–7.34(m,3H),7.32(d,J＝4.0Hz,4H),2.31(s,6H).¹³C NMR(101MHz,CDCl₃)δ:137.2,136.3,134.7,133.7,132.9,132.2,128.8,128.0,127.7,127.7,126.5,126.4,126.2,126.1,125.0,20.9.

HPLC analysis (waters UPC) (OJ-3, 20% CO)₂in methanol,1.0mL/min,214nm)>99％ee:t_R(major)＝24.0min,t_R(minor)＝34.9min.

Claims

1. A compound of formula IV or formula IV', wherein the structure is as follows:

R₅and R₆Independently of one another is hydrogen, C₁-C₄Alkyl, halogen,

is a single bond or a double bond;

or, R₅、R₆Together with the carbon atom to which they are attached to form

2. A compound of formula IV or formula IV' as claimed in claim 1, wherein when Ar is Ar, the compound is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄When aryl of (A) is said R_3a-1Independently is one or more, preferably 1,2, 3 or 4, when a plurality of R's are present_3a-1When R is said_3a-1May be the same or different;

and/or when Ar is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is unsubstituted or R_3a-1Substituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) is independently C₆-C₁₀Aryl of (a), preferably phenyl or naphthyl, more preferably phenyl;

and/or when R_3a-1Independently is C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is independently methyl or tert-butyl, preferably tert-butyl;

and/or when R_7a、R_7b、R_7c、R_8a、R_8bAnd R_8cIndependently is C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is methyl;

and/or when R₅And R₆When independently halogen, said halogen is independently F, Cl, Br or I;

and/or when R₅And R₆Independently is C₆-C₁₀Aryl of (2), said C₆-C₁₀Aryl of (a) is independently phenyl or naphthyl.

3. A compound of formula IV or formula IV' as claimed in claim 2, wherein when Ar is Ar, the compound is_3a、Ar_3b、Ar_3cAnd Ar_3dIndependently is R_3a-1Substituted C₆-C₁₄When aryl of (A) is said R_3a-1Substituted C₆-C₁₀Aryl of is independently

And/or, Ar_3a、Ar_3b、Ar_3cAnd Ar_3dThe same;

and/or, Ar_3a、Ar_3b、Ar_3cAnd Ar_3dSame as Ar_3a、Ar_3b、Ar_3cAnd Ar_3dIs R_3a-1Substituted C₆-C₁₄Aryl of (a);

and/or, R_7a、R_7c、R_8aAnd R_8cSame as R_7bAnd R_8bThe same;

and/or, R_7a、R_7c、R_8aAnd R_8cIs hydrogen, R_7bAnd R_8bSame as R_7bAnd R_8bIs C₁-C₄Alkyl group of (1).

4. A compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to any of the following schemes:

scheme 1:

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R₅and R₆Is hydrogen;

is a single bond or a double bond;

Scheme 2:

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R₅and R₆Is hydrogen;

is a single bond or a double bond;

Scheme 3:

Ar_3a、Ar_3b、Ar_3cand Ar_3dThe same;

R₅and R₆Is hydrogen;

is a single bond;

scheme 4: the compound shown in the formula IV or the formula IV' has any one of the following structures:

5. the crystal form of the compound IV-1 or the compound IV-3 is characterized in that in a single crystal X-ray diffraction spectrum using a radiation source of Ga-Ka,

the single crystal of the compound IV-1 belongs to an orthorhombic system, and the space group is P2₁2₁2₁The unit cell parameters are as follows:

α＝90°，

β＝90°，

gamma 90 deg., unit cell volume

In unit cellThe number of symmetric units Z is 4; the single crystal parameters of the compound IV-1 are preferably as follows:

α＝90°，

β＝90°，

gamma 90 deg., unit cell volume

The number of asymmetric units in the unit cell, Z, is 4; the single crystal parameters of the compound IV-3 are preferably as follows:

6. a process for the preparation of a compound of formula IV or formula IV', comprising the steps of: in an organic solvent, under the action of alkali, a compound shown as a formula V or a formula V' and a compound shown as a formula VI are subjected to a reaction shown as follows;

the method of any one of claims 1-4.

7. A process for the preparation of compound 1, characterized in that it comprises the following steps: in a solvent, under the action of a palladium compound and alkali, carrying out coupling reaction on a compound shown as a formula II and a compound shown as a formula III as shown in the specification; the compound 1 is a compound shown in a formula I or a compound shown in a formula I';

wherein the content of the first and second substances,

x is Cl, Br, I, OTs or OTf;

y is B (OH)₂BPin, Bneo or BF₃K；

Z₁、Z₂、Z₃、W₁、W₂and W₃Independently is N or CR;

each R_1-6And R_1-7Independently is hydrogen or C₁-C₄Alkyl groups of (a);

each R_a-4And R_a-5Independently is hydrogen or C₁-C₄Alkyl groups of (a);

the palladium compound is a compound shown as a formula IV or IV',

the method of any one of claims 1-4;

when the palladium complex is

When the compound 1 is the compound shown in the formula I;

when the palladium complex is

8. The process for preparing compound 1 according to claim 7, wherein when Ar is present₁Is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (a), preferably phenyl or naphthyl, more preferably phenyl;

and/or when Ar is₁Is "one or more hetero atoms selected from N, O and S, the number of hetero atoms is 1-4 "of 5-14 membered heteroaryl, said 5-14 membered heteroaryl is 5-6 membered monocyclic heteroaryl, or 6-14 membered fused heteroaryl, preferably 5-6 membered monocyclic heteroaryl; said 5-6 membered monocyclic heteroaryl is preferably furyl, thienyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, more preferably pyridyl;

and/or when Ar is₂Is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (a), preferably phenyl or naphthyl, more preferably phenyl;

and/or when Ar is₂When the 5-14 membered heteroaryl group is a 5-14 membered heteroaryl group in which "the heteroatom (S) is (are) selected from N, O and S and the number of the heteroatoms is (1) to (4)", the 5-14 membered heteroaryl group is a 5-6 membered monocyclic heteroaryl group or a 6-14 membered fused heteroaryl group, preferably a 5-6 membered monocyclic heteroaryl group; said 5-6 membered monocyclic heteroaryl is preferably furyl, thienyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl or pyrazinyl, more preferably pyridyl;

and/or, when R, R₁、R₂、R₃And R₄Independently halogen, said halogen is independently F, Cl, Br or I, preferably F;

and/or, when R, R₁、R₂、R₃And R₄Independently is R_1-1Substituted C₁-C₄When said alkyl is (a), said R_1-1Independently is one or more, preferably 1,2 or 3, when a plurality of R's are present_1-1When R is said_1-1May be the same or different;

and/or, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-1Substituted C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is methyl;

and/or, when R, R₁、R₂、R₃And R₄Independently is R_1-2Substituted C₁-C₄When it is an alkoxy group, said R_1-2Independently is one or more, preferably 1,2 or 3, when presentPlural R_1-2When R is said_1-2May be the same or different;

and/or, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-2Substituted C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) is independently methoxy or ethoxy;

and/or, when R, R₁、R₂、R₃And R₄Independently is R_1-3Substituted C₆-C₁₄When aryl of (A) is said R_1-3Independently is one or more, preferably 1,2, 3 or 4, when a plurality of R's are present_1-3When R is said_1-3May be the same or different;

and/or, when R, R₁、R₂、R₃And R₄Independently is unsubstituted or R_1-3Substituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) is independently C₆-C₁₀Aryl of (a), preferably phenyl or naphthyl;

and/or when R_1-1、R_1-2、R_1-3And R_1-4Independently halogen, said halogen is independently F, Cl, Br or I, preferably F;

and/or when R_1-1、R_1-2、R_1-3、R_1-4、R_1-5、R_1-6And R_1-7Independently is C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is methyl;

and/or when R_1-1、R_1-2、R_1-3、R_1-4And R_1-5Independently is C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) is independently methoxy or ethoxy;

and/or when R_1-1、R_1-2、R_1-3、R_1-4Independently is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of (a) is independently C₆-C₁₀Aryl of (a), preferably phenyl;

and/or when R_1-5、R_1-6And R_1-7Independently is C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is independently methyl or ethyl;

and/or when R_1-5Is C₁-C₄Alkoxy of (2), said C₁-C₄The alkoxy group of (a) is methoxy or ethoxy;

and/or when R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form R together with the carbon atom to which it is attached_aSubstituted C₆-C₁₄When aryl of (A) is said R_aIndependently is one or more, preferably 1,2 or 3, when a plurality of R's are present_aWhen R is said_aMay be the same or different;

and/or when R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form unsubstituted or R together with the carbon atom to which they are attached_aSubstituted C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (a), preferably phenyl or naphthyl;

and/or when R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form R together with the carbon atom to which it is attached_bWhen the substituted 'heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-4', the R is_bIndependently is one or more, preferably 1,2 or 3, when a plurality of R's are present_bWhen R is said_bMay be the same or different;

and/or when R₁、R₂To the carbon atom to which it is attached, and/or, R₃、R₄Independently form unsubstituted or R together with the carbon atom to which they are attached_bWhen the substituted 'heteroatom is one or more selected from N, O and S, and the number of the heteroatoms is 1-4', the 5-14 membered heteroaryl is 5-6 memberedMonocyclic heteroaryl or 6-14 membered fused heteroaryl, preferably 5-6 membered monocyclic heteroaryl; said 5-6 membered monocyclic heteroaryl is preferably furyl, thienyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl, more preferably thienyl, pyrrolyl, pyridyl or pyrimidinyl; the 6-14 membered fused heteroaryl is preferably 6-10 membered fused heteroaryl, more preferably indolyl, isoindolyl, quinolinyl, isoquinolinyl, and further preferably indolyl;

and/or when R_aAnd R_bWhen independently halogen, said halogen is independently F, Cl, Br or I;

and/or when R_aAnd R_bIndependently is R_a-1Substituted C₁-C₄When said alkyl is (a), said R_a-1Independently is one or more, preferably 1,2 or 3, when a plurality of R's are present_a-1When R is said_a-1May be the same or different;

and/or when R_aAnd R_bIndependently is R_a-2Substituted C₁-C₄When it is an alkoxy group, said R_a-2Independently is one or more, preferably 1,2 or 3, when a plurality of R's are present_a-2When R is said_a-2May be the same or different;

and/or when R_a-1And R_a-2When independently halogen, said halogen is independently F, Cl, Br or I;

and/or when R_a-1、R_a-2、R_a-3、R_a-4And R_a-5Independently is C₁-C₄When there is an alkyl group, said C₁-C₄Alkyl of (a) is independently methyl or ethyl;

and/or when R_a-1、R_a-2And R_a-3Independently is C₁-C₄Alkoxy of (2), said C₁-C₄Alkoxy of (b) is methoxy;

and/or when R_a-1And R_a-2Independently is C₆-C₁₄Aryl of (2), said C₆-C₁₄Aryl of is C₆-C₁₀Aryl of (b), preferably phenyl.

9. The process for the preparation of compound 1 according to claim 7, wherein the compound of formula I or formula I' is according to any of the following schemes:

scheme 1:

x is Cl, Br or OTf;

y is B (OH)₂BPin, Bneo or BF₃K；

Ar₁And Ar₂Independently is C₆-C₁₄Aryl of (a);

Z₁、Z₂、Z₃、W₁、W₂and W₃Independently is N or CR;

each R_1-5Independently is C₁-C₄Alkyl or C₁-C₄Alkoxy group of (a);

each R_1-6And R_1-7Independently is hydrogen or C₁-C₄Alkyl groups of (a);

Each R_a-3Independently is C₁-C₄Alkyl or C₁-C₄Alkoxy group of (a);

scheme 2: the compound shown in the formula I or the formula I' has any one of the following structures:

10. the method according to claim 7, wherein the solvent is an organic solvent or a mixed solvent of an organic solvent and water; the organic solvent is preferably one or more of an alcohol solvent, an aromatic solvent and an ether solvent, and is more preferably an alcohol solvent and/or an aromatic solvent; the alcohol solvent is preferably one or more of ethanol, isopropanol and tert-butanol, and is more preferably tert-butanol; the aromatic hydrocarbon solvent is preferably toluene; the ether solvent is preferably Tetrahydrofuran (THF); when the solvent is a mixed solvent of an organic solvent and water, the volume ratio of the organic solvent to the water is preferably 5:1-10:1, more preferably 8:1-10: 1;

and/or, the base is one or more of alkali metal hydroxide, alkali metal carbonate, alkali metal phosphate and alkali metal alkoxide, preferably alkali metal hydroxide; the alkali metal hydroxide is preferably potassium hydroxide; the alkali metal carbonate is preferably potassium carbonate and/or cesium carbonate; the alkali metal phosphate is preferably potassium phosphate; the alkali metal alkoxide is preferably potassium methoxide and/or potassium tert-butoxide, and is more preferably potassium tert-butoxide;

and/or the molar ratio of the compound shown in the formula III to the compound shown in the formula II is 1:1-5:1, preferably 1:1-2: 1;

and/or the molar ratio of the alkali to the compound shown in the formula II is 1: 1-1, preferably 1:1-3: 1;

and/or the molar concentration of the compound shown in the formula II in the solvent is 0.1-0.5mol/L, preferably 0.1-0.3 mol/L;

and/or the molar ratio of the palladium compound to the compound shown in the formula II is 1:10-1:500, preferably 1:50-1: 200;

and/or the coupling reaction temperature is 30-60 ℃;

and/or the coupling reaction time is 24-48 h.