CN112300214B - Palladium complex, preparation method thereof and preparation method of axial chiral biaromatic compound - Google Patents

Palladium complex, preparation method thereof and preparation method of axial chiral biaromatic compound Download PDF

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CN112300214B
CN112300214B CN201910681991.7A CN201910681991A CN112300214B CN 112300214 B CN112300214 B CN 112300214B CN 201910681991 A CN201910681991 A CN 201910681991A CN 112300214 B CN112300214 B CN 112300214B
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CN112300214A (en
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施世良
申迪
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention provides a palladium compound, a preparation method thereof and a preparation method of an axial chiral biaromatic compound. The invention discloses a compound shown in a formula IV or a formula IV', wherein a palladium compound has a novel structure, is suitable for coupling reaction, and is various in structure, high in yield and good in stereoselectivity. The invention also discloses a shaftThe preparation method of the chiral biaromatic compound has the advantages that the yield of the axial chiral biaromatic 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 of the ee value is more than 90%, the applicability of the substrate is wide, the applicability to heterocyclic substrates is good, and the synthesized axial chiral biaromatic compound has various structures.

Description

Palladium complex, preparation method thereof and preparation method of axial chiral biaromatic compound
Technical Field
The invention relates to a palladium compound, a preparation method thereof and a preparation method of an axial chiral biaromatic compound.
Background
Axial chiral biaryl structures are largely found in natural products and drugs. In particular, in the field of asymmetric catalysis, commonly used chiral catalysts such as chiral diols of binaphthyl structure, monophosphine ligands containing isoquinoline structure, and the like all have axial chiral biaryl structures. Among the numerous methods of constructing axial chirality, palladium-catalyzed asymmetric Suzuki coupling is considered a highly efficient and practical method due to its readily available raw materials and high stability to water and oxygen. In 2000, the Buchwald problem group and the cam problem group simultaneously report that the first palladium-catalyzed asymmetric Suzuki coupling reaction constructs an axial chiral biaryl compound, and then a large number of problem groups sequentially develop and research in the field. a) Yin, j.j.; buchwald, s.l.j.am.chem.soc.2000,122,12051. B) cam, a.n.; crypy, K.V.L.2000,1723. C) Bermejo, A.; ros, a.; fernandez, r.; lassalaetta, j.m.j.am.chem.soc.2008,130,15798. D) Uozumi, y; matsuura, t.; arakawa, t.; yamada, Y.M.A.Angew.Chem., int.Ed.2009,48,2708. E) Yamamoto, t.; akai, y.; nagata, y; suginome, M.Angew.Chem., int.Ed.2011,50,8844. F) Xu, g.; fu, W.; liu, g.; senanayake, c.h.; tang, w.j.am.chem.soc.2014,136,570. G) awai, k.; tatumi, R.; nakahodo, t.; fujihara, h. Angew.Chem., int.Ed.2008,47,6917, despite extensive research, there are several challenges that are currently in need of resolution. First, heterocyclic containing substrates are difficult to build into axial chiral products due to their strong coordination capacity, weak reactivity, poor stability and low spin energy barrier; second, a general catalyst compatible with a wide variety of functional groups has not been achieved; thirdly, constructing ortho-tetra-substituted biaryl compounds remains a difficult problem in asymmetric Suzuki coupling reactions; fourth, the achievement of high enantioselectivity in the past often relies on substitution of ortho-position with large steric hindrance, which also limits the range of substrates; fifth, mild reaction conditions and lower catalyst usage remain the pursued goal. Sixth, highly correspondingly selective reactions are mainly achieved by limited chiral phosphine ligands, which also limits the development of such reactions. We envisage accelerating oxidative addition and inhibiting heterocyclic substrate complexation poisoning by using strongly powered N-heterocyclic carbene ligands and palladium complexes, the highest ee value of the asymmetric Suzuki reaction catalyzed by chiral N-heterocyclic carbene-palladium complexes 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 and developed efficient synthesis methods for synthesizing axial chiral biaryl compounds by catalyzing asymmetric Suzuki coupling reactions with chiral azacyclo-carbene-palladium complexes, which would have 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 when the existing palladium-catalyzed coupling reaction is used for constructing an axial chiral biaromatic compound, and provides a palladium compound, a preparation method thereof and a preparation method of the axial chiral biaromatic compound. The biaromatic 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 proposal.
The invention provides a compound shown as a formula IV or a formula IV', and the structure of the compound is shown as follows:
wherein Ar is 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently is unsubstituted or R 3a-1 Substituted C 6 -C 14 Aryl of (a); each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R is 8c Independently hydrogen or C 1 -C 4 Alkyl of (a);
R 5 and R is 6 Independently hydrogen, C 1 -C 4 Alkyl, halogen,Or C 6 -C 10 Aryl of (a); wherein R is 5-1 And R is 5-2 Independently hydrogen or C 1 -C 4 Alkyl of (a); />Is a single bond or a double bond;
alternatively, R 5 、R 6 And carbon atoms attached thereto form together
In a preferred embodiment of the present invention, when Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently R is 3a-1 Substituted C 6 -C 14 R is said to be aryl 3a-1 May independently be one or more, for example 1, 2, 3 or 4, when there are a plurality of R 3a-1 When said R is 3a-1 May be the same or different.
In a preferred embodiment of the present invention, when Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently is unsubstituted or R 3a-1 Substituted C 6 -C 14 Said C 6 -C 14 Aryl groups of (2) are independently C 6 -C 10 Preferably phenyl or naphthyl, more preferably phenyl.
In a preferred embodiment of the invention, when R 3a-1 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butylMethyl or t-butyl is preferred, and t-butyl is more preferred.
In a preferred embodiment of the invention, when R 7a 、R 7b 、R 7c 、R 8a 、R 8b And R is 8c Independently C 1 -C 4 When alkyl is said C 1 -C 4 The 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 5 、R 6 、R 5-1 And R is 5-2 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) are independently methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
In a preferred embodiment of the invention, when R 5 And R is 6 When independently halogen, the halogen is independently F, cl, br or I.
In a preferred embodiment of the invention, when R 5 And R is 6 Independently C 6 -C 10 Said C 6 -C 10 Is independently phenyl or naphthyl.
In a preferred embodiment of the present invention, when Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently R is 3a-1 Substituted C 6 -C 14 R is said to be aryl 3a-1 Substituted C 6 -C 10 Aryl groups of (2) are independently preferably
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments): ar (Ar) 3a 、Ar 3b 、Ar 3c And Ar is a group 3d The same applies.
In a preferred embodiment of the present invention, certain groups of the compounds of formula IV are defined as follows (undefined groupsGroups as described in any of the previous schemes): ar (Ar) 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Identical Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Is R 3a-1 Substituted C 6 -C 14 Aryl groups of (a).
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments): r is R 7a 、R 7c 、R 8a And R is 8c Identical, R 7b And R is 8b The same applies.
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments): r is R 7a 、R 7c 、R 8a And R is 8c Is hydrogen, R 7b And R is 8b Identical, R 7b And R is 8b Is C 1 -C 4 Is a hydrocarbon group.
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments):
Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently is unsubstituted or R 3a-1 Substituted C 6 -C 14 Aryl of (a); each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen;is a single bond or a double bond;
alternatively, R 5 And R is 6 And carbon atoms attached thereto form together
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments):
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently R is 3a-1 Substituted C 6 -C 14 Aryl of (a); each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen;is a single bond or a double bond;
alternatively, R 5 And R is 6 And carbon atoms attached thereto form together
In a preferred embodiment of the invention, certain groups of the compounds of formula IV or formula IV' are defined as follows (undefined groups are as described in any of the previous embodiments):
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently R is 3a-1 Substituted C 6 -C 14 Aryl of (a); each R 3a-1 Independently C 1 -C 4 Preferably t-butyl;
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen; Is a single bond.
In a preferred embodiment of the present invention, the compound of formula IV may have any one of the following structures:
in a preferred embodiment of the present invention, the compound of formula IV' may have any one 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, R) - (SIPE) Pd (cin) Cl), in a single crystal X-ray diffraction spectrum using Ga-K alpha as a radiation source,
the single crystal of the compound IV-1 belongs to an orthorhombic crystal system, and the space group is P2 1 2 1 2 1 The unit cell parameters are as follows:α＝90°，/>β＝90°，/>gamma=90°, unit cell volume->The number of asymmetric units in the unit cell z=4, the single crystal parameters can be the parameters in table 1;
the single crystal of the compound IV-3 belongs to an orthorhombic crystal system, and the space group is P2 1 2 1 2 1 The unit cell parameters are as follows:α＝90°，/>β＝90°，/>gamma=90°, unit cell volume->The number of asymmetric units in the unit cell z=4, the single crystal parameters can be the parameters 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 compound IV-1 or compound IV-3 monocrystal, 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 in an atmosphere of an alkane solvent preferably comprises the steps of: the filtrate is placed in a container of alkane solvent and allowed to stand, more preferably the filtrate is placed in a jar containing alkane solvent and allowed to stand.
The chlorinated alkane solvent may be a conventional chlorinated alkane solvent in the art, preferably chloroform and/or dichloromethane, for example chloroform. The amount of the chlorinated alkane 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 to mass ratio of the chlorinated alkane solvent to the compound IV-1 or the compound IV-3 is 0.1 to 0.5L/g, for example: 0.2L/g.
The alkane solvent may be a conventional alkane solvent in the art, preferably n-pentane and/or n-hexane, e.g., n-hexane.
The filtration may be conventional in the art for such operations, preferably with a filter membrane.
The method for producing a single crystal may further comprise the step of selecting under a microscope after the single crystal is produced.
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, carrying out the following reaction between a compound shown as a formula V or a formula V' and a compound shown as a formula VI;
Wherein Ar is 3a 、Ar 3b 、Ar 3c 、Ar 3d 、R 5 、R 6 、R 7a 、R 7b 、R 7c 、R 8a 、R 8b 、R 8c Andall as described above.
In the preparation method of the compound shown as the formula IV or the formula IV', the reaction conditions and operations can be conventional conditions and operations in the field of such reactions.
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 a coupling reaction between a compound shown in a formula II and a compound shown in a formula III; the compound 1 is a compound shown in a formula I or a compound shown in a formula I';
wherein,
x is Cl, br, I, OTs or OTf;
y is B (OH) 2 、BPinBneo/>Or BF 3 K；
Ar 1 And Ar is a group 2 Independently C 6 -C 14 Or "heteroatom selected from one or more of N, O and S, a 5-to 14-membered heteroaryl group having 1 to 4 heteroatoms;
Z 1 、Z 2 、Z 3 、W 1 、W 2 and W is 3 Independently N or CR;
each R, R 1 、R 2 、R 3 And R is 4 Independently is hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R 1-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R 1-2 Substituted C 1 -C 4 Alkoxy, unsubstituted or R 1-3 Substituted C 6 -C 14 Aryl, unsubstituted or R 1-4 The substituted hetero atom is one or more of N, O and S, and the hetero atom number is C of 1-4 5 -C 14 Heteroaryl group of (C),
Each R 1-1 、R 1-2 、R 1-3 And R is 1-4 Independently is halogen, C 1 -C 4 Alkyl, C of (2) 1 -C 4 Alkoxy, or C 6 -C 14 Aryl of (a);
each R 1-5 Independently is hydroxy, C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R 1-6 And R is 1-7 Independently hydrogen or C 1 -C 4 Alkyl of (a);
alternatively, R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Or aryl of (C), or unsubstituted or R b The substituted hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4 and is 5-14 membered heteroaryl;
each R a And R is b Independently is hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R a-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R a-2 Substituted C 1 -C 4 Alkoxy group of (C),
Each R a-1 And R is a-2 Independently is halogen, C 1 -C 4 Alkyl, C of (2) 1 -C 4 Alkoxy, or C 6 -C 14 Aryl of (a);
each R a-3 Independently is hydroxy, C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R a-4 And R is a-5 Independently hydrogen or C 1 -C 4 Alkyl of (a);
the palladium compound is shown as a formula IV or a formula IV',
wherein Ar is 3a 、Ar 3b 、Ar 3c 、Ar 3d 、R 5 、R 6 、R 7a 、R 7b 、R 7c 、R 8a 、R 8b And R is 8c All as described above;
when the palladium complex isIn the process, the compound 1 is shown as a formula I;
when the palladium complex isIn the process, the compound 1 is shown as a formula I'.
In a preferred embodiment of the present invention, when Ar 1 Is C 6 -C 14 Said C 6 -C 14 Aryl of (2) is C 6 -C 10 Aryl groups of (a), such as phenyl or naphthyl, preferably phenyl;
in a preferred embodiment of the present invention, when Ar 1 In the case of a 5-14 membered heteroaryl group having 1 to 4 heteroatoms selected from one or more of N, O and S, 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 Ar 2 Is C 6 -C 14 Said C 6 -C 14 Aryl of (2) is C 6 -C 10 Aryl groups of (a), such as phenyl or naphthyl, preferably phenyl;
in a preferred embodiment of the present invention, when Ar 2 In the case of a 5-14 membered heteroaryl group having 1 to 4 heteroatoms selected from one or more of N, O and S, 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 invention, when R, R 1 、R 2 、R 3 And R is 4 When independently halogen, the halogen is independently F, cl, br or I, preferably F.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-1 Substituted C 1 -C 4 When alkyl is said R 1-1 May independently be one or more, for example 1, 2 or 3, when there are a plurality of R 1-1 When said R is 1-1 May be the same or different.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-1 Substituted C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) may independently be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, preferably methyl.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-2 Substituted C 1 -C 4 When alkoxy is in the presence of R 1-2 May independently be one or more, for example 1, 2 or 3, when there are a plurality of R 1-2 When said R is 1-2 May be the same or different.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-2 Substituted C 1 -C 4 When alkoxy is said C 1 -C 4 The alkoxy groups of (a) may independently be 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, R 1 、R 2 、R 3 And R is 4 Independently R is 1-3 Substituted C 6 -C 14 R is said to be aryl 1-3 May independently be one or more, for example 1, 2, 3 or 4, when there are a plurality of R 1-3 When said R is 1-3 May be the same or different.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-3 Substituted C 6 -C 14 Said C 6 -C 14 The aryl groups of (a) can independently be C 6 -C 10 Preferably phenyl or naphthyl.
In a preferred embodiment of the invention, when R 1-1 、R 1-2 、R 1-3 And R is 1-4 When independently halogen, the halogen is independently F, cl, br or I, preferably F.
In a preferred embodiment of the invention, when R 1-1 、R 1-2 、R 1-3 、R 1-4 、R 1-5 、R 1-6 And R is 1-7 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) may independently be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl, preferably methyl.
In a preferred embodiment of the invention, when R 1-1 、R 1-2 、R 1-3 、R 1-4 And R is 1-5 Independently C 1 -C 4 When alkoxy is said C 1 -C 4 The alkoxy groups of (a) may independently be methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy orT-butoxy, preferably methoxy or ethoxy.
In a preferred embodiment of the invention, when R 1-1 、R 1-2 、R 1-3 、R 1-4 Independently C 6 -C 14 Said C 6 -C 14 The aryl groups of (a) can independently be C 6 -C 10 Preferably phenyl.
In a preferred embodiment of the invention, when R 1-5 、R 1-6 And R is 1-7 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The 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 1-5 Is C 1 -C 4 When alkoxy is said C 1 -C 4 The 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 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R a Substituted C 6 -C 14 R is said to be aryl a May independently be one or more, for example 1, 2 or 3, when there are a plurality of R a When said R is a May be the same or different.
In a preferred embodiment of the invention, when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Said C 6 -C 14 Aryl of (2) is C 6 -C 10 Preferably phenyl or naphthyl.
In a preferred embodiment of the invention, when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R b Substituted "hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4" 5-14 membered heteroaryl, R b May independently be one or more, for example 1, 2 or 3, when there are a plurality of R b When said R is b May be the same or different.
In a preferred embodiment of the invention, when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b When the substituted "heteroatom is selected from one or more of N, O and S, and the heteroatom number is 1-4" 5-14 membered heteroaryl, the 5-14 membered heteroaryl may be 5-6 membered monocyclic heteroaryl or 6-14 membered fused heteroaryl, preferably 5-6 membered monocyclic heteroaryl. The 5-to 6-membered monocyclic heteroaryl group may be furyl, thienyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl, preferably thienyl, pyrrolyl, pyridyl or pyrimidinyl, for exampleThe 6-14 membered fused heteroaryl group may be a 6-10 membered fused heteroaryl group, such as indolyl, isoindolyl, quinolinyl, isoquinolinyl, preferably indolyl, such as +. >
In a preferred embodiment of the invention, when R a And R is b When independently halogen, the halogen is independently F, cl, br or I.
In a preferred embodiment of the invention, when R a And R is b Independently R is a-1 Substituted C 1 -C 4 When alkyl is said R a-1 May independently be one or more, for example 1, 2 or 3, when there are a plurality of R a-1 When said R is a-1 May be the same or different.
In a preferred embodiment of the invention, when R a And R is b Independently is unsubstituted or R a-1 Substituted C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) may independently be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
In a preferred embodiment of the invention, when R a And R is b Independently R is a-2 Substituted C 1 -C 4 When alkoxy is in the presence of R a-2 May independently be one or more, for example 1, 2 or 3, when there are a plurality of R a-2 When said R is a-2 May be the same or different.
In a preferred embodiment of the invention, when R a And R is b Independently is unsubstituted or R a-2 Substituted C 1 -C 4 When alkoxy is said C 1 -C 4 The alkoxy groups of (a) may independently be methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.
In a preferred embodiment of the invention, when R a-1 And R is a-2 When independently halogen, the halogen is independently F, cl, br or I.
In a preferred embodiment of the invention, when R a-1 、R a-2 、R a-3 、R a-4 And R is a-5 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) may independently be 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 a-1 、R a-2 And R is a-3 Independently C 1 -C 4 When alkoxy is said C 1 -C 4 The alkoxy groups of (a) may independently be methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy, preferably methoxy.
In a preferred embodiment of the invention, when R a-1 And R is a-2 Independently C 6 -C 14 Said C 6 -C 14 The aryl group of (C) may be C 6 -C 10 For example phenyl.
In a preferred embodiment of the invention, when R a-3 、R a-4 And R is a-5 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl groups of (a) may independently be methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl.
In a preferred embodiment of the invention, when R a-3 Is C 1 -C 4 When alkoxy is said C 1 -C 4 The alkoxy groups of (a) may independently be methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy.
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-1 Substituted C 1 -C 4 When alkyl is said R 1-1 Substituted C 1 -C 4 Independently of one another, are preferably-CF 3 。
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-2 Substituted C 1 -C 4 When alkoxy is in the presence of R 1-2 Substituted C 1 -C 4 Alkoxy groups of (a) are independently preferably-OBn or/>
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-3 Substituted C 6 -C 14 R is said to be aryl 1-3 Substituted C 6 -C 14 Aryl groups of (2) are independently preferably
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently isWhen said->Independently preferably->
In a preferred embodiment of the invention, when R, R 1 、R 2 、R 3 And R is 4 Independently isWhen said->Independently preferably->
In a preferred embodiment of the invention, when R a And R is b Independently isSaid->Preferably
In a preferred embodiment of the invention, when R a And R is b Independently isWhen said->Preferably
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 described in any of the previous embodiments):
x is Cl, br or OTf;
y is B (OH) 2 BPin, bneo or BF 3 K；
Ar 1 And Ar is a group 2 Independently C 6 -C 14 Aryl of (a);
Z 1 、Z 2 、Z 3 、W 1 、W 2 and W is 3 Independently N or CR;
each R, R 1 、R 2 、R 3 And R is 4 Independently is hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R 1-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R 1-2 Substituted C 1 -C 4 Alkoxy, or unsubstituted or R 1-3 Substituted C 6 -C 14 Aryl of (a);
each R 1-1 、R 1-2 、R 1-3 And R is 1-4 Independently is halogen, C 1 -C 4 Or C is an alkyl group of (C) 1 -C 4 Alkoxy groups of (a);
each R 1-5 Independently C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R 1-6 And R is 1-7 Independently hydrogen or C 1 -C 4 Alkyl of (a);
alternatively, R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Or aryl of (C), or unsubstituted or R b The substituted hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4 and is 5-14 membered heteroaryl;
each R a And R is b Independently hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted C 1 -C 4 Alkyl, unsubstituted C 1 -C 4 Alkoxy, or
Each R a-3 Independently C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a).
In a preferred embodiment of the present invention, the compound of 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 hydrocarbon solvent and an ether solvent, and more preferably an alcohol solvent and/or an aromatic hydrocarbon solvent. The alcohol solvent is preferably one or more of ethanol, isopropanol and tert-butanol, more preferably tert-butanol. The aromatic 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 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, more preferably potassium tert-butoxide.
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, for example 1.2:1, 1.3:1 or 2:1.
In the coupling reaction, the molar ratio of the base to the compound of formula II is preferably 1:1:1, more preferably 1:1 to 3:1, for example 1.3:1, 2:1 or 2.5:1.
In the coupling reaction, the molar concentration of the compound of formula II in the solvent is preferably 0.1 to 0.5mol/L, more preferably 0.1 to 0.3mol/L, for example 0.2mol/L or 0.25mol/L.
In the coupling reaction, the molar ratio of the palladium complex to the compound represented by formula II is preferably 1:10 to 1:500, more preferably 1:50 to 1:200, for example 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 to 48 hours.
The coupling reaction is preferably carried out under a protective gas atmosphere, which may be a protective gas conventional in the art, such as nitrogen.
In the coupling reaction, preferably, after the reaction is finished, the method may further include a post-treatment operation, and the post-treatment may include the following steps: separating and purifying the reaction liquid. The separation and purification are 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, the C 1 -C 4 Alkyl is methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl or isobutyl.
In the present invention, the term alkoxy denotes the resulting group after the alkyl group is attached to the oxygen atom, i.eR is alkyl. C (C) 1 -C 4 Alkoxy of (a) means methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy or tert-butoxy.
In the present invention, the term "aryl" refers to an aromatic group having a specified number of carbon atoms, preferably a monocyclic, bicyclic or tricyclic aromatic group, and when bicyclic or tricyclic, each ring satisfies the shock rule. C of the invention 6-10 Aryl of (a) refers to an aromatic group containing 6 to 10 carbon atoms, such as phenyl or naphthyl.
In the present invention, the term heteroaryl means a stable mono-, bi-or tri-ring of up to 14 atoms in each ring, wherein at least one ring is aromatic and contains 1-4 heteroatoms selected from O, N and S. Heteroaryl groups within the scope of this definition include 5-6 membered monocyclic heteroaryl groups, 6-14 membered fused heteroaryl groups. 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 the fused monocyclic heteroaryl group on an aryl, heteroaryl, cycloalkyl or heterocycloalkyl group, examples include, but are not limited to, acridinyl, carbazolyl, cinnolinyl, quinoxalinyl, indolyl, isoindolyl, benzopyrazolyl, benzothienyl, benzofuranyl, quinolinyl, isoquinolinyl, pyrrolopyridinylpyrazinyl, tetrahydroquinolinyl or
On the basis of conforming to the common knowledge in the field, the above preferred conditions can be arbitrarily combined to obtain the preferred examples of the invention.
The reagents and materials used in the present invention are commercially available.
The invention has the positive progress effects that:
(1) The axial chiral biaromatic compound prepared by the preparation method has high yield, strong reaction stereoselectivity, ee value up to more than 85% and most of more than 90%.
(2) The preparation method disclosed by the invention is wide in substrate applicability, has good applicability to heterocyclic substrates, and the synthesized axial chiral biaromatic compound has various structures.
(3) The palladium compound has novel structure, is suitable for coupling reaction, and has various structures, high yield and good stereoselectivity of the synthesized axial chiral biaromatic compound.
Drawings
FIG. 1 is a single crystal view 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 means of the following examples, which are not intended to limit the scope of the invention. The experimental methods, in which specific conditions are not noted in the following examples, were selected according to conventional methods and conditions, or according to the commercial specifications.
Preparation of Compound A series of Compounds
Example 1:1, 3-bis (2, 6-bis ((R) -1- (3, 5-di-t-butylphenyl) ethyl) -4-methylphenyl) -4, 5-dihydro-1H-imidazole salt (Compound V-1)
Step 1: synthesis of intermediate 2
To a 500mL round bottom flask was added 1, 3-bis (diphenylphosphinopropane) nickel dichloride (2.48 g,4.6 mmol), 100mL of tetrahydrofuran, diisobutylaluminum hydride (122 mL,183.1 mmol), the reaction was also cooled to 0℃and intermediate 1 was dissolved in 100mL of tetrahydrofuran, slowly added dropwise to the reaction solution, the reaction solution was transferred to room temperature and stirred for 2 hours, and then the reaction was also cooled to 0℃and 2-methoxy-4, 5-tetramethyl-1, 3, 2-dioxaborolan (30 mL,228.9 mmol) was slowly added dropwise, and the reaction solution was transferred to an 80℃oil bath and heated and stirred for 24 hours. The reaction was stopped, the reaction solution was transferred to a cold trap at 0 ℃ and quenched slowly by dropping water, part of the tetrahydrofuran solution was removed under reduced pressure, an appropriate amount of ethylenediamine tetraacetic acid aqueous solution and ethyl acetate solution were added, stirred for 3 hours, extracted with ethyl acetate, and the organic phase was dried over anhydrous sodium sulfate, concentrated and purified by column chromatography to give oily intermediate 2 (44.5 g, yield=85%).
Step 2: synthesis of 2, 6-bis (1- (3, 5-di-t-butylphenyl) vinyl) -4-methylaniline (intermediate 4)
To a 100mL pressure-resistant bottle was added 2, 6-dibromo-4-methylaniline (43.9 g,128.3 mmol), [1, 3-bis (2, 6-diisopropylbenzene) imidazol-2-ylidene ] (3-chloropyridine) palladium dichloride (729 mg,1.2 mmol), potassium hydroxide (9.8 g,174.9 mmol), intermediate 2 (15.4 g,58.3 mmol), and a 100mL tetrahydrofuran solution, and the mixture was heated at 100℃for 12 hours. The reaction was stopped, the silica gel column was too short, washed with ethyl acetate, concentrated under reduced pressure, and purified by column chromatography to give intermediate 4 (27 g, yield=87%)
Step 3: synthesis of 2, 6-bis ((R) -1- (3, 5-di-t-butylphenyl) ethyl) -4-methylaniline (intermediate 5)
To a 300mL reaction flask was added intermediate 4 (18.5 g,34.5 mmol), 120mL MeOH, and a dry vial was added rhodium bis (norbornadiene) tetrafluoroborate ((NBD) 2 RhBF 4 0.3 mol%), (Rc, sp) -DuanPhos (0.36 mol%), DCM (12 mL) was stirred for 15min and then added to a 300mL reaction flask, and the mixture was vented at 30℃with 80atm H 2 After 48 hours of reaction, the reaction was stopped. Methanol was removed under reduced pressure, the silica gel column was too short, washed with ethyl acetate, concentrated, and purified by column chromatography to give oily intermediate 5 (13.0 g, yield=70%). 1 H NMR(400MHz,CDCl 3 )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)。 13 C 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.(c＝0.40,CHCl 3 )
Step 4: synthesis of N, N-bis (2, 6-di ((R) -1- (3, 5-di-tert-butylphenyl) ethyl) -4-methylphenyl) oxamide (Compound 6)
Intermediate 5 (1.89 g,3.5 mol), tetrahydrofuran 15 in a 50mL round bottom bottlemL, triethylamine (535. Mu.L, 3.9 mol), the reaction was cooled to 0deg.C, oxalyl chloride (163. Mu.L, 1.9 mol) was slowly added dropwise, the reaction was warmed to room temperature, and stirring was continued overnight. The reaction was stopped, the reaction mixture was quenched by adding an appropriate amount of saturated aqueous sodium bicarbonate solution, extracted with dichloromethane, and the organic phase was dried over anhydrous sodium sulfate, concentrated, and purified by column chromatography to give intermediate 6 (1.68 g, yield=85%) as a white foam. 1 H 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). 13 C 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.(c＝0.37,CHCl 3 ) HRMS (ESI) calculated value (C 80 H 116 N 3 O 2 [M+H] + ) 1150.9062, found 1150.9054.
Step 5: synthesis of N, N-bis (2, 6-di ((R) -1- (3, 5-di-tert-butylphenyl) ethyl) -4-methylphenyl) ethane-1, 2-diamine (intermediate 7)
To a 100mL round bottom flask was added intermediate 6 (3 g,2.65 mol), tetrahydrofuran (30 mL), the reaction mixture was cooled to 0deg.C, lithium aluminum hydride (540.0 mg,13.5 mol) was added in portions, the reaction mixture was warmed to reflux, and stirring was continued for 24h. Stopping the reaction, adding 15% potassium hydroxide aqueous solution (0.5 mL) into the reaction solution, quenching the reaction, stirring the mixture at room temperature for 15min, adding a proper amount of magnesium sulfate, performing suction filtration, washing with ethyl acetate, drying the organic phase by anhydrous sodium sulfate, and concentrating; the dried mixture was dissolved in 30mL of toluene solution, and BH was added dropwise thereto 3 -Me 2 S (5.4mL.2.0M in THF,10.8mmol), reflux and stirring for 12h. The reaction was stopped, 1M hydrochloric acid (20 mL) was slowly added to the reaction solution, stirred for 3h, extracted with dichloromethane, and the organic phase was further alkalified with aqueous sodium hydroxide solution, and then dried and concentrated to give intermediate 7 (1.8 g, yield=62%) as a white solid. 1 H NMR(400MHz,CDCl 3 )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).. 13 C NMR(101MHz，CDCl 3 )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.(c＝0.31,CHCl 3 ) HRMS (ESI) calculated value (C 80 H 117 N 2 [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-imidazole salt (Compound V-1)
Into a 50mL eggplant-shaped bottle was added Compound 7 (1.5 g,2.35 mmol), NH 4 Cl (108.6 mg,2.03 mmol), 4.7mL triethyl orthoformate, after displacement with nitrogen, the mixture was reacted at 115℃for 20 hours, followed by concentration on a short silica gel column and purification by column chromatography to give the white compound V-1 (1.4 g, yield=90%). 1 H NMR(400MHz,CDCl 3 )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). 13 C 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。(c＝0.31,CHCl 3 ) HRMS (ESI) calculated value (C 81 H 115 N 2 [M+H] + ) 1115.9055, found 1115.9038.
Referring to the procedure 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 、R 5 、R 6 、R 7a 、R 7b 、R 7c 、R 8a 、R 8b And R is 8c All as described above.
In a glove box, compound V (0.3 mmol), potassium t-butoxide (30.3 mg,0.27 mmol), tetrahydrofuran (1.2 mL, 0.25M) were added sequentially to an 8mL vial and stirred at room temperature for 4h. Then [ Pd (eta) 3 -cin)(μ-Cl)] 2 (77.7 mg,0.15 mmol) was added thereto, and stirring was continued at room temperature for 12 hours. Stopping the reaction, passing the reaction solution through a short silica gel column, washing with ethyl acetate, concentrating an 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)
Following general procedure A, compound V-1 (345.2 mg,0.3 mmol) was added to an 8mL vial, and 279.8mg (yield: 68%, compound IV-1) was isolated as a pale yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.90,CHCl 3 ).HRMS (MALDI) calculated (C 90 H 123 N 2 Pd[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 general procedure A, compound V-2 (55.2 mg,0.06 mmol) was added to an 8mL vial, and 37.1mg (yield: 60%) of Compound IV-2 was isolated as a yellow foamy solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.14,CHCl 3 ) HRMS (MALDI) calculated value (C 66 H 75 N 2 Pd[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 procedure A, compound V-3 (420.0 mg,0.6 mmol) was added to an 8mL vial, and 430.2mg (yield: 77%) of Compound IV-3 was isolated as a pale solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.45,CHCl 3 ) HRMS (ESI) calculated value (C 58 H 59 N 2 Pd[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)
Following general procedure A, compound V-4 (127.0 mg,0.1 mmol) was added to an 8mL vial, and 430.2mg (yield: 77%, compound IV-4) was isolated as a yellow solid. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.30,CHCl 3 ) HRMS (ESI) calculated value (C 100 H 125 N 2 Pd[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 general ruleUsing method A, compound V-5 (102.0 mg,0.11 mmol) was added to an 8mL vial, and 95.1mg (yield: 75%, compound IV-5) of a yellow solid was isolated. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.80,CHCl 3 ) HRMS (MALDI) calculated value (C 76 H 77 N 2 Pd[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 general procedure A, compound V-6 (100.0 mg,0.12 mmol) was added to an 8mL vial, and 89.2mg (yield: 71%, compound IV-6) of yellow solid was isolated. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.70,CHCl 3 ) HRMS (ESI) calculated value (C 68 H 61 N 2 Pd[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 general procedure A, compound V-7 (100.0 mg,0.12 mmol) was added to an 8mL vial, and 89.2mg (yield: 71%, compound IV-7) of yellow solid was isolated. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.40,CHCl 3 ) HRMS (ESI) calculated value (C 58 H 57 N 2 Pd[M-Cl] + ) 883.3572, found 883.3539.
Example 10: single crystal diffraction experiments of Compounds IV-1 and IV-3
1. Single crystal cultivation: the compound IV-1 (30 mg) or IV-3 (20 mg) was dissolved in chloroform (3 mL), filtered through a filter membrane, and the filtrates were placed in jars containing n-hexane (15 mL) and allowed to stand, respectively, to obtain the single crystals.
2. The test parameters are shown in tables 1 and 2 above.
3. Test results: the configuration of compound IV-1 and compound IV-3 is determined by single crystal diffraction.
Example 11: optimization of reaction conditions
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 is determined by chiral HPLC of the chiral stationary phase.
Example 12: synthesis of axial chiral biaromatic compound
General procedure A to a 15mL Schlemk bottle equipped with a stirrer was added compound IV-1 (2.8 mg, 2. Mu. Mol), potassium hydroxide (22.4 mg,0.40 mmol), aryl bromide II (0.2 mmol), aryl boronic acid III (0.24 mmol) and tert-butanol (1.0 mL, 0.2M) in sequence. After the atmosphere was changed to a nitrogen atmosphere, the reaction solution was stirred at 50℃for 24 hours. Stopping the reaction, diluting the reaction solution by using a short silica gel column and ethyl acetate, concentrating an organic phase, purifying by using column chromatography to obtain a target product, measuring an ee value by using chiral HPLC, and measuring the configuration of the compound by using a single crystal diffraction experiment.
Example 13
General procedure B to a 15mL Schlemk bottle equipped with a stirrer was added compound IV-1 (2.8 mg, 4. Mu. Mol), cesium carbonate (162.9 mg,0.50 mmol), aryl bromide II (0.2 mmol), aryl boronic acid III (0.40 mmol) and tert-butanol/water (9:1, 1.0mL, 0.2M) in sequence. After the atmosphere was changed to a nitrogen atmosphere, the reaction solution was stirred at 60℃for 24 hours. Stopping the reaction, diluting the reaction solution by using a short silica gel column and ethyl acetate, concentrating an organic phase, purifying by using column chromatography to obtain a target product, measuring an ee value by using chiral HPLC, and measuring the configuration of the compound by using a single crystal diffraction experiment.
Example 14
General procedure C to a 15mL Schlemk bottle equipped with a stirrer was added compound IV-1 (1.4 mg, 1. Mu. Mol), potassium tert-butoxide (29.2 mg,0.26 mmol), aryl bromide II (0.2 mmol), aryl boronic acid III (0.26 mmol) and toluene/water (9:1, 0.8mL, 0.25M) in sequence. After the atmosphere was changed to a nitrogen atmosphere, the reaction solution was stirred at 30℃for 24 hours. Stopping the reaction, diluting the reaction solution by using a short silica gel column and ethyl acetate, concentrating an organic phase, purifying by using column chromatography to obtain a target product, measuring an ee value by using chiral HPLC, and measuring the configuration of the compound by using a single crystal diffraction experiment.
Example 15
Compound I-1 was prepared as a white solid according to general procedure A in 91% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.23,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1mL/min,230 nm) gave 97% ee:t R (major)＝5.9min,t R (minor)＝7.0min./>
The compound I-2 was prepared as a white solid in 98% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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. (c＝1.45,CHCl 3 ) HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 95% ee t R (mior)＝6.8min,t R (major)＝9.3min.
Compound I-3 was prepared as a colorless oil according to general procedure A in 92% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.24,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 90% ee t R (major)＝6.1min,t R (minor) =9.4 min hrms (ESI) calculated C 27 H 24 NO[M+H] + m/z 378.1852, found 378.1856.
Compound I-4 is prepared as a white solid in 85% yield according to general procedure C. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.63,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm)92％ee:t R (major)＝7.8min,t R (minor) =9.9 min. Hrms (ESI) calculated C 23 H 24 NO 2 [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 examples R Compound I-4 (20 mg) at (major) =7.8 min was dissolved in chloroform (1 mL), filtered with a filter membrane, and the filtrate was placed in a nuclear magnetic resonance tube and allowed 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. Test 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. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.20,CHCl 3 ) HPLC analysis (OD-H, 15% IPA in cyclohexane, 1.0mL/min,220 nm) gave 99% ee t R (minor)＝9.7min,t R (major) =12.4 min HRMS (ESI) calculated value C 20 H 15 O 2 [M+H] + m/z 287.1067, found 287.1069.
Compound I-7 is prepared as a colorless oil according to general procedure C in yield96％。 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.20,CHCl 3 ) HPLC analysis (AD-H, 10% IPA in cyclohexane, 1.0mL/min,254 nm) gave 92% ee t R (minor)＝15.9min,t R (minor) =21.0 min HRMS (ESI) calculated C 17 H 15 O 2 [M+H] + m/z 251.1067, found 251.1070.
Compound I-8 was prepared as a colorless oil according to general procedure C in 98% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.58,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 90% ee t R (major)＝14.9min,t R (minor) =16.2 min. Hrms (ESI) calculated C 22 H 15 O 3 [M-H]-m/z327.1027, found 327.1023>
Compound I-9 was prepared as a colorless oil according to general procedure C in 86% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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. (c＝0.30,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 93% ee t R (major)＝14.9min,t R (minor) =16.9 min hrms (ESI) calculated C 25 H 24 NO[M+H] + m/z 354.1852, found 354.1849.
Compound I-10 was prepared as a brown oil according to general procedure B in 81% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.50,CHCl 3 ) HPLC analysis (OD-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 90% ee t R (major)＝8.9min,t R (minor)＝9.5min.
Compound I-11 was prepared as a yellow oil in 75% yield according to general procedure B. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.68,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 85% ee t R (major)＝11.9min,t R (minor) =15.7 min hrms (ESI) calculated C 17 H 16 N[M+H] + m/z 234.1277, found 234.1278.
Compound I-12 was prepared as a brown oil according to general procedure B in 81% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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. 19 F NMR(376MHz,CDCl 3 )δ:-60.8.(c＝1.18,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 91% ee t R (major)＝4.5min,t R (minor) =6.4 min hrms (EI) calculated value C 19 H 15 OF 3 [M] + m/z 316.1075, found 316.1067.
Compound I-13 is prepared as a white solid according to general procedure A in 89% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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. 19 F NMR(376MHz,CDCl 3 )δ:-60.8.(c＝1.33,CHCl 3 ) HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 92% ee t R (minor)＝16.4min,t R (major) =25.9 min. Hrms (EI) calculated value C 21 H 15 OF[M] + m/z286.1158, found 286.1159.
Compound I-14 is prepared as a yellow solid in 90% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ:154.6,147.3,135.7,134.1,134.0 132.8,130.3,130.1,129.1,129.0,128.1,126.9,125.6,125.0,124.1,123.9,123.8,122.6,121.8,113.4,56.6.(c＝1.48,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 97% ee t R (major)＝10.0min,t R (minor) =12.0 min hrms (EI) calculated value C 21 H 15 NO 3 [M] + m/z 329.1052, found 329.1045.
Compound I-15 was prepared as a colorless oil according to general procedure A in 95% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 CNMR(101MHz,CDCl 3 )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.(c＝1.30,CHCl 3 ) HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 95% ee t R (minor)＝16.4min,t R (major) =25.9 min. Hrms (EI) calculated value C 22 H 15 N[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. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.20,CHCl 3 ) HPLC analysis (OD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 95% ee t R (minor)＝7.7min,t R (major) =8.3 min. Hrms (ESI) calculated C 20 H 19 O 2 [M+H] + m/z 290.1380, found 291.1379.
Compound I-17 was prepared as colorless oil in 97% yield according to general procedure A using 1-naphthyl-trifluoromethanesulfonate (55.2 mg,0.2mmol,1.0 equiv) and 2-methoxy-1-naphthaleneboronic acid (48.5 mg,0.24mmol,1.2 equiv). 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.70,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 96% ee t R (major)＝6.2min,t R (minor)＝7.6min.
Compound I-18:using 1-bromo-2-methoxynaphthalene (47.4 mg,0.2mmol,1.0 equiv) and 2-methylphenylboronic acid (32.6 mg,0.24mmol,1.2 equiv) and 0.5mol% of the catalyst according to general procedure A, a colorless oil was prepared in 97% yield. 1 H 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). 13 C NMR(101MHz,CDCl 3 )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./> (c＝1.25,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 93% ee t R (major)＝4.3min,t R (minor)＝5.0min.
Compound I-18:using 1-bromo-2-methoxynaphthalene (47.4 mg,0.2mmol,1.0 equiv) and 4, 5-tetramethyl-2- (2-methylphenyl) -1,3, 2-dioxaborolan (52.3 mg,0.24mmol,1.2 equiv) and 0.5mol% catalyst, a colorless oil was prepared in 99%,94% ee.
Compound I-18:using 1-bromo-2-methoxynaphthalene (47.4 mg,0.2mmol,1.0 equiv) and 5, 5-dimethyl-2- (2-methylphenyl) -1,3, 2-dioxaborolan (49.0 mg,0.24mmol,1.2 equiv) and 0.5mol% catalyst, a colorless oil was prepared in 91% yield, 93% ee.
Compound I-18:using 1-bromo-2-methoxynaphthalene (47.4 mg,0.2mmol,1.0 equiv) and potassium (2-methylphenyl) trifluoroborate (79.2 mg,0.4mmol,2.0 equiv), a colorless oil was prepared in 98% yield, 90% ee, according to general procedure B.
Compound I-19A colorless oil was prepared according to general procedure A using 4, 5-tetramethyl-2- (2-methyl-1-naphthyl) -1,3, 2-dioxaborolan (53.6 mg,0.2mmol,1.0 equiv), 1-bromoisoquinoline (83.2 mg,0.4mmol,2.0 equiv) and 2mol% catalyst in 60% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.78,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 90% ee t R (major)＝10.3min,t R (minor) =10.9 min hrms (ESI) calculated C 20 H 16 N[M+H] + m/z 270.1277, found 270.1283.
Compound I-21 was prepared as a colorless oil in 88% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.50,CHCl 3 ) HPLC analysis (AD-H, 3% IPA in cyclohexane, 1.0mL/min,254 nm) gave 93% ee t R (minor)＝11.9min,t R (major) =18.2 min. Hrms (ESI) calculated value C 20 H 16 N[M+H] + m/z 270.1277, found 270.1279.
Compound I-22:a yellow oil was prepared according to general procedure A in 94% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 CNMR(101MHz,CDCl 3 )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./>(c＝1.20,CHCl 3 ) HPLC analysis (AD-H, 3% IPA in cyclohexane, 1.0mL/min,254 nm) gave 94% ee t R (minor)＝10.2min,t R (major) =11.1 min hrms (ESI) calculated value C 20 H 16 N[M+H] + m/z 270.1277, found 270.1276.
Compound I-22:a yellow oil was prepared according to general procedure A in 87% ee yield.
Compound I-23 was prepared as colorless oil in 91% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.03,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 95% ee t R (major)＝17.8min,t R (minor) =19.6 min hrms (ESI) calculated C 20 H 16 NO[M+H] + m/z 286.1226, found 286.1227.
Compound I-24 was prepared as colorless oil in 84% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 CNMR(101MHz,CDCl 3 )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.(c＝1.50,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 94% ee t R (minor)＝8.8min,t R (major) =10.0 min hrms (ESI) calculated value C 20 H 16 N[M+H] + m/z 270.1277, found 270.1278.
Compound I-25 was prepared as a colorless oil in 82% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.28,CHCl 3 ) HPLC analysis (IC, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 90% ee t R (major)＝11.4min,t R (minor) =12.0 min hrms (ESI) calculated value C 20 H 16 ON[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 (400 MHz, 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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.33,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 96% ee t R (minor)＝13.1min,t R (major) =14.4 min. Hrms (ESI) calculated C 20 H 16 NO[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. 1 H NMR(400MHz,CDCl 3 )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). 13 CNMR(101MHz,CDCl 3 )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.(c＝1.28,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 95% ee t R (minor)＝14.0min,t R (major) =15.0 min hrms (ESI) calculated value C 20 H 16 NO[M+H] + m/z 286.1226, found 286.1230.
Compound I-28 was prepared as a yellow oil in 79% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.18,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 92% ee t R (major)＝11.1min,t R (minor) =13.5 min. Hrms (ESI) calculated C 21 H 18 NO[M+H] + m/z300.1383, found 300.1383.
Compound I-29 was prepared as a yellow oil in 94% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.20,CHCl 3 ) HPLC analysis (OJ-H, 5% IPA in cyclohexane, 1.0mL/min,254 nm) gave 93% ee t R (minor)＝9.8min,t R (major) =16.0 min hrms (ESI) calculated value C 17 H 16 NO[M+H] + m/z 250.1226, found 250.1226.
Compound I-30 was prepared as a yellow oil in 79% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.40,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 94% ee t R (minor)＝9.8min,t R (major) =11.3 min. Hrms (ESI) calculated C 19 H 15 N 2 [M+H] + m/z 271.1230, found 271.1233.
Compound I-31 was prepared as a white solid in 93% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.48,CHCl 3 ) HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 99% ee:t R (minor)＝8.4min,t R (major) =9.9 min. Hrms (ESI) calculated C 24 H 20 NO[M+H] + m/z 338.1539, found 338.1542.
Compound I-32 was prepared as a white solid in 82% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.75,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,230 nm) gave 90% ee t R (major)＝8.8min,t R (minor) =12.1 min hrms (ESI) calculated C 21 H 20 NO[M+H] + m/z 302.1539, found 302.1546.
Compound I-33 was prepared as a colorless oil in 97% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.35,CHCl 3 ) HPLC analysis (OJ-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 86% ee t R (minor)＝8.4min,t R (major) =11.7 min. Hrms (EI) calculated value C 15 H 14 S[M] + m/z 274.0816, found 274.0820.
Compound I-34 was prepared as a white solid in 98% yield according to general procedure B. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝1.20,CHCl 3 ) HPLC analysis (AD-H, 10% IPA in cyclohexane, 1.0mL/min,230 nm) gave 95% ee t R (minor)＝19.9min,t R (major) =26.3 min. Hrms (ESI) calculated C 19 H 15 N 2 O[M+H] + m/z 287.1179, found 287.1182.
Compound I-35 was prepared as a white solid in 57% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )δ:155.1,134.2,129.5,129.4,128.1,126.4,125.4,123.6,119.7,114.4,57.1.(c＝0.39,CHCl 3 ) HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,280 nm) gave 96% ee:t R (major)＝8.3min,t R (minor)＝9.5min.
Compound I-36 was prepared as a white solid in 62% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.31,CHCl 3 ) HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,254 nm) gave 92% ee t R (major)＝7.0min,t R (minor)＝9.1min.
Compound I-37 was prepared as a white solid in 85% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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. 19 F NMR(376MHz,CDCl 3 )δ:-113.9.(c＝0.93,CHCl 3 ) HPLC analysis (AD-H, 1% IPA in cyclohexane, 1.0mL/min,220 nm) gave 95% ee t R (major)＝5.0min,t R (minor) =6.5 min. Hrms (EI) calculated value C 18 H 15 OF[M] + m/z 266.1107, found 226.1102.
Compound I-38 was prepared as a brown solid in 54% yield according to general procedure A. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.25,CHCl 3 ) HPLC analysis (AD-H, 5% IPA in cyclohexane, 1.0mL/min,280 nm) gave 94% ee t R (major)＝22.5min,t R (minor)＝27.5min.HRMS(ESI)calculated
Compound I-39A white solid was prepared according to general procedure A using 1, 4-dibromonaphthalene (57.2 mg,0.2mmol,1.0 equiv), (2-methoxy-1-naphthyl) boronic acid (145.5 mg,0.72mmol,3.6 equiv), potassium hydroxide (56 mg,1.0mmol,5.0 equiv), 2mol% catalyst and 2mL t-butanol in 74% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 C NMR(101MHz,CDCl 3 )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.(c＝0.58,CHCl 3 ) HPLC analysis (IC, 1% IPA in cyclohexane, 1.0mL/min,220 nm)>99％ee:t R (minor)＝8.0min,t R (major) =16.0 min hrms (ESI) calculated value C 32 H 25 O 2 [M+H] + m/z 441.1849, found 441.1857.
Compound I-40A white solid was prepared according to general procedure A using 1, 4-dibromonaphthalene (57.2 mg,0.2mmol,1.0 equiv), (2-methyl-1-naphthyl) boronic acid (133.9 mg,0.72mmol,3.6 equiv), potassium hydroxide (56 mg,1.0mmol,5.0 equiv), 2mol% catalyst and 2mL t-butanol in 60% yield. 1 H NMR(400MHz,CDCl 3 )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). 13 CNMR(101MHz,CDCl 3 )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.(c＝0.50,CHCl 3 ) HPLC analysis (waters UPC) (OJ-3, 20% CO 2 indomethacin, 1.0mL/min,214 nm)>99％ee:t R (major)＝24.0min,t R (minor)＝34.9min./>

Claims (25)

1. A compound of formula IV or formula IV', characterized by the structure shown below:
wherein Ar is 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently is unsubstituted or R 3a-1 A substituted phenyl group; each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
R 7a 、R 7b 、R 7c 、R 8a 、R 8b and R is 8c Independently hydrogen or C 1 -C 4 Alkyl of (a);
R 5 and R is 6 Independently hydrogen, C 1 -C 4 Or C is an alkyl group of (C) 6 -C 10 Aryl of (a); wherein,is a single bond or a double bond;
alternatively, R 5 、R 6 And carbon atoms attached thereto form together
2. A compound of formula IV or formula IV' as claimed in claim 1,
when Ar is 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently R is 3a-1 In the case of substituted phenyl, R is 3a-1 Independently one or more;
and/or when R 3a-1 Independent and independentThe ground is C 1 -C 4 When alkyl is said C 1 -C 4 Independently methyl or t-butyl;
and/or when R 7a 、R 7b 、R 7c 、R 8a 、R 8b And R is 8c Independently C 1 -C 4 When alkyl is said C 1 -C 4 Is methyl;
and/or when R 5 And R is 6 Independently C 6 -C 10 Said C 6 -C 10 Is independently phenyl or naphthyl.
3. The compound of formula IV or formula IV' according to claim 2, wherein when Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently R is 3a-1 In the case of substituted phenyl, R is 3a-1 1, 2, 3 or 4 independently;
and/or when there are a plurality of R 3a-1 When said R is 3a-1 The same or different;
and/or when R 3a-1 Independently C 1 -C 4 When alkyl is said C 1 -C 4 The alkyl group of (2) is tert-butyl.
4. The compound of formula IV or formula IV' according to claim 2, wherein when Ar 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Independently R is 3a-1 In the case of substituted phenyl, R is 3a-1 The substituted phenyl groups are independently
And/or R 7a 、R 7c 、R 8a And R is 8c Identical, R 7b And R is 8b The same applies.
5. The compound of formula IV or formula IV' as defined in claim 4,
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
and/or R 7a 、R 7c 、R 8a And R is 8c Identical, R 7b And R is 8b The same; ar (Ar) 3a 、Ar 3b 、Ar 3c And Ar is a group 3d Is R 3a-1 A substituted phenyl group;
and/or R 7a 、R 7c 、R 8a And R is 8c Is hydrogen, R 7b And R is 8b Identical, R 7b And R is 8b Is C 1 -C 4 Is a hydrocarbon group.
6. The compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to the following scheme:
scheme 1:
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently is unsubstituted or R 3a-1 A substituted phenyl group; each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen; wherein,is a single bond or a double bond;
alternatively, R 5 And R is 6 And carbon atoms attached thereto form together
7. The compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to the following scheme:
scheme 2:
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently R is 3a-1 A substituted phenyl group; each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen; wherein,is a single bond or a double bond;
alternatively, R 5 And R is 6 And carbon atoms attached thereto form together
8. The compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to the following scheme:
scheme 3:
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently R is 3a-1 A substituted phenyl group; each R 3a-1 Independently C 1 -C 4 Alkyl of (a);
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen; wherein,is a single bond.
9. The compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to the following scheme:
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d Independently R is 3a-1 A substituted phenyl group; each R 3a-1 Is tert-butyl;
Ar 3a 、Ar 3b 、Ar 3c and Ar is a group 3d The same;
R 7a 、R 7c 、R 8a and R is 8c Is hydrogen, R 7b And R is 8b Independently C 1 -C 4 And R is an alkyl group of 7b And R is 8b The same;
R 5 and R is 6 Is hydrogen; wherein,is a single bond.
10. The compound of formula IV or formula IV 'according to claim 1, wherein the compound of formula IV or formula IV' is according to the following scheme:
scheme 4: the compound shown as the formula IV or the formula IV' has any one of the following structures:
11. a crystalline form of compound IV-1 or compound IV-3, characterized in that, in a single crystal X-ray diffraction spectrum using Ga-K alpha as the radiation source,
the single crystal of the compound IV-1 belongs to an orthorhombic crystal system, and the space group is P2 1 2 1 2 1 The unit cell parameters are as follows:α＝90°，/>β＝90°，/>gamma=90°, unit cell volume->The number of asymmetric units in the unit cell z=4;
the single crystal of the compound IV-3 belongs to an orthorhombic crystal system, and the space group is P2 1 2 1 2 1 The unit cell parameters are as follows:α＝90°，/>β＝90°，/>gamma=90°, unit cell volume->The number of asymmetric units z=4 in the unit cell.
12. A crystalline form of compound IV-1 or compound IV-3 according to claim 11, wherein in a single crystal X-ray diffraction spectrum using a radiation source of Ga-kα, the single crystal parameters of compound IV-1 are:
；
and/or, the single crystal parameters of the compound IV-3 are as follows:
。
13. 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, carrying out the following reaction between a compound shown as a formula V or a formula V' and a compound shown as a formula VI;
wherein Ar is 3a 、Ar 3b 、Ar 3c 、Ar 3d 、R 5 、R 6 、R 7a 、R 7b 、R 7c 、R 8a 、R 8b 、R 8c Andthe method of any one of claims 1-10.
14. A process for the preparation of compound 1, characterized in that it comprises the steps of: in a solvent, under the action of palladium complex and alkali, the compound shown as the formula II and the compound shown as the formula II are mixedThe compound shown in III is subjected to the coupling reaction shown below; wherein the solvent is an organic solvent or a mixed solvent of the organic solvent and water, and the organic solvent is one or more of an alcohol solvent, an aromatic hydrocarbon solvent and an ether solvent; the alkali is one or more of alkali metal hydroxide, alkali metal carbonate, alkali metal phosphate and alkali metal alkoxide; the compound 1 is a compound shown in a formula I, a compound shown in a formula I
Wherein,
x is Cl, br, I, OTs or OTf;
y is B (OH) 2 BPin, bneo or BF 3 K, performing K; the BPin isThe Bneo is +.>
Ar 1 And Ar is a group 2 Independently phenyl, or a 6 membered monocyclic heteroaryl group having "N as a heteroatom, 1 to 3 heteroatoms";
Z 1 、Z 2 、Z 3 、W 1 、W 2 and W is 3 Independently N or CR;
each R, R 1 、R 2 、R 3 And R is 4 Independently is hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R 1-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R 1-2 Substituted C 1 -C 4 Alkoxy, unsubstituted or R 1-3 Substituted C 6 -C 14 Aryl, unsubstituted or R 1-4 The substituted hetero atom is one or more of N, O and S, and the hetero atom number is C of 1-4 5 -C 14 Heteroaryl group of (C),
Each R 1-1 、R 1-2 、R 1-3 And R is 1-4 Independently is halogen, C 1 -C 4 Alkyl, C of (2) 1 -C 4 Alkoxy, or C 6 -C 14 Aryl of (a);
each R 1-5 Independently is hydroxy, C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R 1-6 And R is 1-7 Independently hydrogen or C 1 -C 4 Alkyl of (a);
alternatively, R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Or aryl of (C), or unsubstituted or R b The substituted hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4 and is 5-14 membered heteroaryl;
each R a And R is b Independently is hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R a-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R a-2 Substituted C 1 -C 4 Alkoxy group of (C),
Each R a-1 And R is a-2 Independently is halogen, C 1 -C 4 Alkyl, C of (2) 1 -C 4 Alkoxy, or C 6 -C 14 Aryl of (a);
each R a-3 Independently is hydroxy, C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R a-4 And R is a-5 Independently hydrogen or C 1 -C 4 Alkyl of (a);
the palladium compound is shown as a formula IV or a formula IV',
wherein Ar is 3a 、Ar 3b 、Ar 3c 、Ar 3d 、R 5 、R 6 、R 7a 、R 7b 、R 7c 、R 8a 、R 8b 、R 8c Andthe method of any one of claims 1-10;
when the palladium complex isIn the process, the compound 1 is shown as a formula I;
when the palladium complex isIn the process, the compound 1 is shown as a formula I'.
15. A process for the preparation of compound 1 according to claim 14,
when Ar is 1 When the heteroatom is 6-membered monocyclic heteroaryl with N, 1-3 heteroatoms, the 6-membered monocyclic heteroaryl is pyridyl, pyridazinyl and pyrimidinyl;
and/or when Ar 2 When the heteroatom is 6-membered monocyclic heteroaryl with N, 1-3 heteroatoms, the 6-membered monocyclic heteroaryl is pyridyl, pyridazinyl and pyrimidinyl;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently halogen The halogen is independently F, cl, br or I;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-1 Substituted C 1 -C 4 When alkyl is said R 1-1 Independently one or more;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-1 Substituted C 1 -C 4 When alkyl is said C 1 -C 4 Is methyl;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-2 Substituted C 1 -C 4 When alkoxy is in the presence of R 1-2 Independently one or more;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-2 Substituted C 1 -C 4 When alkoxy is said C 1 -C 4 Is independently methoxy or ethoxy;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-3 Substituted C 6 -C 14 R is said to be aryl 1-3 Independently one or more;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-3 Substituted C 6 -C 14 Said C 6 -C 14 Aryl groups of (2) are independently C 6 -C 10 Aryl of (a);
and/or when R 1-1 、R 1-2 、R 1-3 And R is 1-4 When independently halogen, the halogen is independently F, cl, br or I;
and/or when R 1-1 、R 1-2 、R 1-3 And R is 1-4 Independently C 1 -C 4 When alkyl is said C 1 -C 4 Is methyl;
and/or when R 1-1 、R 1-2 、R 1-3 、R 1-4 Independently C 1 -C 4 When alkoxy is said C 1 -C 4 Is independently methoxy or ethoxy;
and/or when R 1-1 、R 1-2 、R 1-3 、R 1-4 Independently C 6 -C 14 Said C 6 -C 14 Aryl groups of (2) are independently C 6 -C 10 Aryl of (a);
and/or when R 1-5 、R 1-6 And R is 1-7 Independently C 1 -C 4 When alkyl is said C 1 -C 4 Independently methyl or ethyl;
and/or when R 1-5 Is C 1 -C 4 When alkoxy is said C 1 -C 4 Alkoxy of (a) is methoxy or ethoxy;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R a Substituted C 6 -C 14 R is said to be aryl a Independently one or more;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Said C 6 -C 14 Aryl of (2) is C 6 -C 10 Aryl of (a);
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R b Substituted "hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4" 5-14 membered heteroaryl, R b Independently one or more;
and/or when R 1 、R 2 Connected with itAnd/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b When the substituted hetero atom is selected from one or more of N, O and S and the hetero atom number is 1-4, the 5-14 membered heteroaryl is 5-6 membered monocyclic heteroaryl or 6-14 membered thick heteroaryl;
And/or when R a And R is b When independently halogen, the halogen is independently F, cl, br or I;
and/or when R a And R is b Independently R is a-1 Substituted C 1 -C 4 When alkyl is said R a-1 Independently one or more;
and/or when R a And R is b Independently R is a-2 Substituted C 1 -C 4 When alkoxy is in the presence of R a-2 Independently one or more;
and/or when R a-1 And R is a-2 When independently halogen, the halogen is independently F, cl, br or I;
and/or when R a-1 、R a-2 、R a-3 、R a-4 And R is a-5 Independently C 1 -C 4 When alkyl is said C 1 -C 4 Independently methyl or ethyl;
and/or when R a-1 、R a-2 And R is a-3 Independently C 1 -C 4 When alkoxy is said C 1 -C 4 Alkoxy of (2) is methoxy;
and/or when R a-1 And R is a-2 Independently C 6 -C 14 Said C 6 -C 14 Aryl of (2) is C 6 -C 10 Aryl groups of (a).
16. A process for the preparation of compound 1 according to claim 15,
when Ar is 1 In the case of a 6-membered monocyclic heteroaryl group having "N as a heteroatom and 1 to 3 heteroatoms", the 6-membered monocyclic heteroaryl group isHeteroaryl is pyridinyl;
and/or when Ar 2 When the heteroatom is 6-membered monocyclic heteroaryl with N heteroatoms and 1-3 heteroatoms, the 6-membered monocyclic heteroaryl is pyridyl;
and/or when R, R 1 、R 2 、R 3 And R is 4 When independently halogen, said halogen is independently F;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-1 Substituted C 1 -C 4 When alkyl is said R 1-1 1, 2 or 3 independently;
and/or when there are a plurality of R 1-1 When said R is 1-1 The same or different;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-2 Substituted C 1 -C 4 When alkoxy is in the presence of R 1-2 1, 2 or 3;
and/or when there are a plurality of R 1-2 When said R is 1-2 The same or different;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently R is 1-3 Substituted C 6 -C 14 R is said to be aryl 1-3 1, 2, 3 or 4 independently;
and/or when there are a plurality of R 1-3 When said R is 1-3 May be the same or different;
and/or when R, R 1 、R 2 、R 3 And R is 4 Independently is unsubstituted or R 1-3 Substituted C 6 -C 14 Said C 6 -C 14 Aryl of (a) is independently phenyl or naphthyl;
and/or when R 1-1 、R 1-2 、R 1-3 And R is 1-4 When independently halogen, said halogen is independently F;
and/or when R 1-1 、R 1-2 、R 1-3 、R 1-4 Independently C 6 -C 14 Said C 6 -C 14 Aryl of (2) is phenyl;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R a Substituted C 6 -C 14 R is said to be aryl a 1, 2 or 3 independently;
and/or when there are a plurality of R a When said R is a The same or different;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Said C 6 -C 14 Aryl of (2) is phenyl or naphthyl;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form R b Substituted "hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4" 5-14 membered heteroaryl, R b 1, 2 or 3 independently;
and/or when there are a plurality of R b When said R is b May be the same or different;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b The substituted hetero atom is selected from one or more of N, O and S, the hetero atom number is 1-4, and the 5-14 membered heteroaryl is 5-6 membered monocyclic heteroaryl;
and/or when R a And R is b Independently R is a-1 Substituted C 1 -C 4 When alkyl is said R a-1 1, 2 or 3 independently;
and/or when there are a plurality of R a-1 When said R is a-1 The same or different;
and/or when R a And R is b Independently R is a-2 Substituted C 1 -C 4 When alkoxy is in the presence of R a-2 1, 2 or 3 independently;
and/or when there are a plurality of R a-2 When said R is a-2 The same or different;
and/or when R a-1 And R is a-2 Independently C 6 -C 14 Said C 6 -C 14 Is phenyl.
17. A process for the preparation of compound 1 according to claim 16, wherein when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b The substituted hetero atom is one or more of N, O and S, and when the hetero atom number is 1-4 and the 5-14 membered heteroaryl is 5-6 membered monocyclic heteroaryl, the 5-6 membered monocyclic heteroaryl is furyl, thienyl, pyrrolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl;
and/or when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b When the substituted hetero atom is one or more of N, O and S and the hetero atom number is 1-4, the 5-14 membered heteroaryl is 6-14 membered condensed heteroaryl.
18. A process for the preparation of compound 1 according to claim 17, wherein when R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b When the substituted hetero atom is selected from one or more of N, O and S and the hetero atom number is 1-4, the 5-14 membered heteroaryl is 6-10 membered condensed heteroaryl.
19. A process for the preparation of compound 1 according to claim 17,
when R is 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b The substituted hetero atom is one or more of N, O and S, and when the hetero atom number is 1-4 and the 5-14 membered heteroaryl is 6-14 membered fused heteroaryl, the 6-14 membered fused heteroaryl is indolyl, isoindolyl, quinolinyl and isoquinolinyl.
20. A process for the preparation of compound 1 according to claim 19,
when R is 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R b The substituted hetero atom is one or more of N, O and S, and when the hetero atom number is 1-4 and the 5-14 membered heteroaryl is 6-14 membered fused heteroaryl, the 6-14 membered fused heteroaryl is indolyl.
21. The method for preparing the compound 1 according to claim 14, wherein the compound shown in the formula I or the compound shown in the formula I' is the following scheme:
scheme 1:
x is Cl, br or OTf;
y is B (OH) 2 BPin, bneo or BF 3 K；
Ar 1 And Ar is a group 2 Is phenyl;
Z 1 、Z 2 、Z 3 、W 1 、W 2 and W is 3 Is CR;
each R, R 1 、R 2 、R 3 And R is 4 Independently is hydrogen, hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted or R 1-1 Substituted C 1 -C 4 Alkyl, unsubstituted or R 1-2 Substituted C 1 -C 4 Alkoxy, or unsubstituted or R 1-3 Substituted C 6 -C 14 Aryl of (a);
each R 1-1 、R 1-2 、R 1-3 And R is 1-4 Independently is halogen, C 1 -C 4 Or C is an alkyl group of (C) 1 -C 4 Alkoxy groups of (a);
each R 1-5 Independently C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a);
each R 1-6 And R is 1-7 Independently hydrogen or C 1 -C 4 Alkyl of (a);
alternatively, R 1 、R 2 To which are attached carbon atoms, and/or R 3 、R 4 Together with the carbon atoms to which they are attached independently form unsubstituted or R a Substituted C 6 -C 14 Or aryl of (C), or unsubstituted or R b The substituted hetero atom is selected from one or more of N, O and S, and the hetero atom number is 1-4 and is 5-14 membered heteroaryl;
each R a And R is b Independently hydroxy, aldehyde, amino, nitro, cyano, halogen, unsubstituted C 1 -C 4 Alkyl, unsubstituted C 1 -C 4 Alkoxy, or
Each R a-3 Independently C 1 -C 4 Alkyl or C of (2) 1 -C 4 Alkoxy groups of (a).
22. The method for preparing the compound 1 according to claim 14, wherein the compound shown in the formula I or the compound shown in the formula I' is the following scheme:
scheme 2: the compound 1 has any one of the following structures:
/>
23. the method for producing compound 1 according to claim 14, wherein the solvent is an organic solvent or a mixed solvent of an organic solvent and water; the organic solvent is an alcohol solvent and/or an aromatic solvent;
and/or, the alkali is alkali metal hydroxide;
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;
and/or the molar ratio of the alkali to the compound shown as the formula II is 1:1-3:1;
and/or the molar concentration of the compound shown as the formula II in the solvent is 0.1-0.5mol/L;
and/or the molar ratio of the palladium compound to the compound shown as the formula II is 1:10-1:500;
and/or, the coupling reaction temperature is 30-60 ℃;
and/or the coupling reaction time is 24-48h.
24. The method for preparing compound 1 according to claim 23, wherein the alcohol solvent is one or more of ethanol, isopropanol and tert-butanol;
And/or, the aromatic solvent is toluene;
and/or when the solvent is a mixed solvent of an organic solvent and water, the volume ratio of the organic solvent to the water is 5:1-10:1;
and/or, the alkali metal hydroxide is potassium hydroxide;
and/or, the alkali metal carbonate is potassium carbonate and/or cesium carbonate;
and/or, the alkali metal phosphate is potassium phosphate;
and/or the alkali metal alkoxide is potassium methoxide and/or 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 1:1-2:1;
and/or the molar ratio of the alkali to the compound shown as the formula II is 1:1;
and/or the molar concentration of the compound shown as the formula II in the solvent is 0.1-0.3mol/L;
and/or the molar ratio of the palladium compound to the compound shown as the formula II is 1:50-1:200.
25. The process for the preparation of compound 1 according to claim 23, wherein the alcoholic solvent is t-butanol;
and/or when the solvent is a mixed solvent of an organic solvent and water, the volume ratio of the organic solvent to the water is 8:1-10:1; and/or, the alkali metal alkoxide is potassium tert-butoxide.
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