CN114957103B - Axial chiral halogenated biaryl compound and preparation method thereof - Google Patents

Axial chiral halogenated biaryl compound and preparation method thereof Download PDF

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CN114957103B
CN114957103B CN202210764992.XA CN202210764992A CN114957103B CN 114957103 B CN114957103 B CN 114957103B CN 202210764992 A CN202210764992 A CN 202210764992A CN 114957103 B CN114957103 B CN 114957103B
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alkyl
alkoxy
aryl
halogen
butyl
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CN114957103A (en
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游书力
郑冬松
张文文
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Shanghai Institute of Organic Chemistry of CAS
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Shanghai Institute of Organic Chemistry of CAS
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Abstract

The invention discloses an axial chiral halogenated biaryl compound and a preparation method thereof. The invention provides a preparation method of a compound 3, which comprises the following steps of carrying out halogenation reaction on a compound shown in a formula I and a compound shown in a formula II in the presence of a rhodium catalyst, silver salt and copper salt in an organic solvent under the atmosphere of protective gas to obtain the compound 3; the compound 3 is a compound shown in a formula III and/or a compound shown in a formula III'. The preparation method has the advantages of easily available raw materials, better substrate universality, high reaction efficiency and high enantioselectivity.

Description

Axial chiral halogenated biaryl compound and preparation method thereof
Technical Field
The invention relates to an axial chiral halogenated biaryl compound and a preparation method thereof.
Background
The axichiral molecules are widely present in natural products with biological activity, they can also be widely used as ligands or catalysts in the asymmetric catalytic field (Kozlowski,M.C.;Morgan,B.J.;Linton,E.C.Chem.Soc.Rev.2009,38,3193-3207. Bringmann,G.;Gulder,T.;Gulder,T.A.M.;Breuning,M.Chem.Rev.2011,111,563-639.Xie,J.-H.;Zhou,Q.-L.Acc.Chem.Res.2008,41,581-593.Akiyama,T.Chem.Rev.2007,107,5744-5758.Rueping,M.; Kuenkel,A.;Atodiresei,I.Chem.Soc.Rev.2011,40,4539-4549.)., where the axichiral iodo compounds can be used as catalysts in a large number of applications in catalyzing reactions such as asymmetric oxidative dearomatization, asymmetric functionalization of the carbonyl alpha position (Flores a.; cots e.; bergles j.; K.Adv.Synth.Catal.2019,361,2-25.Kumar R.; singh f.v.; takenaga n; dohi T. CHEM ASIAN J.2021,16, 1-21). At present, few chiral iodides have been reported for asymmetric catalytic synthesis, and particularly, few chiral iodides have been reported for construction by asymmetric C-H activation. In 2013, the Yu Jinquan group reported that Pd-catalyzed C-H iodination with chiral amino acids as ligands was able to produce iodo compounds with central chirality in 85% yield and 98% ee value (Chu L.; wang X.; C.; moore C.E.; rheingold A.L.; yu J.; Q.J.am. Chem. Soc.2013,135, 16344-16347). Until now, there is only one example of an asymmetric C-H activation construct with an axial chiral iodide. In 2014, the book force subject group used chiral amino acids as ligands, and implemented Pd catalyzed asymmetric C-H iodination reaction by kinetic resolution method to construct axial chiral iodinated biaryl compound (reaching 73% yield and 94% ee), but the method was low in efficiency, and the asymmetric control was poor (GaoD.—W.; gu Q.; you S.—L.ACS catalyst.2014, 4, 2741-2745).
The preparation method of the iodinated biaryl compounds which are reported in the prior art and are synthesized by asymmetric C-H activation has the technical problems of single method, low efficiency and poor enantioselectivity, and the problems are needed to be solved.
Disclosure of Invention
The invention aims to solve the technical problems of single method, low efficiency and poor enantioselectivity of the existing preparation method of the chiral iodinated biaryl compound of the asymmetric C-H activation synthesis axis, and provides a preparation method of the chiral halogenated biaryl compound of the axis. The preparation method has the advantages of easily available raw materials, better substrate universality, high reaction efficiency and high enantioselectivity.
The invention provides a preparation method of an axial chiral halogenated biaryl compound 3, which comprises the following steps: in the presence of rhodium catalyst, silver salt and copper salt in an organic solvent under the atmosphere of protective gas, carrying out halogenation reaction on a compound shown in a formula I and a compound shown in a formula II to obtain a compound 3; the compound 3 is a compound shown in a formula III and/or a compound shown in a formula III';
x is halogen;
r 1 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8, aryl of C 6-C12, or aryl of C 6-C12 substituted with one or more R 1-1;
R 1-1 is halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
R 2 is hydrogen, halogen or alkyl of C 1-C8;
R 3 is halogen, hydroxymethyl, aldehyde, acetyl, cyano, C 1-C8 alkyl, C 1-C8 alkoxy, C 2-C8 oxaalkyl or
R 3-1 is hydrogen or alkyl of C 1-C8;
R 4 is aldehyde, cyano, carboxyl, trifluoromethyl, C 1-C8 alkyl, C 1-C8 alkoxy or
R 4-1 is hydrogen or alkyl of C 1-C8;
R 5 is hydrogen, halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
R 6 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8, aryl of C 6-C12, or aryl of C 6-C12 substituted with one or more R 6-1;
r 6-1 is halogen, alkyl of C 1-C8 or alkoxy of C 1-C8.
Or R 2 and R 3 together with the carbon atoms in between form: aryl of C 6-C14, aryl of C 6-C14 substituted with one or more R 23-1, 5-10 membered heteroaryl, or 5-10 membered heteroaryl substituted with one or more R 23-2; when multiple substituents are present, the same or different; the hetero atom is selected from N, O and S, and the number of the hetero atoms is 1-3 in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 23-2;
R 23-1 and R 23-2 are independently halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
or R 1、R2 and R 3 together with the carbon atoms in between form: aryl of C 10-C14 or aryl of C 6-C10 and cycloalkenyl of C 3-C7;
or R 4 and R 5 together with the carbon atom therebetween form a C 5-C8 cycloalkenyl, a C 6-C14 aryl, a C 6-C14 aryl substituted with one or more R 45-1, a 5-10 membered heteroaryl, or a 5-10 membered heteroaryl substituted with one or more R 45-2; when multiple substituents are present, the same or different; the hetero atom is selected from N, O and S, and the number of the hetero atoms is 1-3 in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 45-2;
R 45-1 and R 45-2 are independently halogen, alkyl of C 1-C8 or alkoxy of C 1-C8.
In some embodiments of the application, certain groups in said compound 3 are defined as follows (groups not mentioned are as described in any of the embodiments of the application)
When X is halogen, the halogen may be Cl, br or I.
When R 1 is halogen, the halogen may be F, cl, br or I.
When R 1 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl, more preferably methyl.
When R 1 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy, tert-butoxy.
When R 1 is an aryl group of C 6-C12, the aryl group of C 6-C12 may be phenyl, naphthyl or phenanthryl.
When R 1 is aryl of C 6-C12 substituted by one or more R 1-1, the number of R 1-1 is 1-3.
When R 1 is an aryl group of C 6-C12 substituted with one or more R 1-1, the aryl group of C 6-C12 may be phenyl or naphthyl.
When R 1-1 is halogen, the halogen may be F, cl, br or I.
When R 1-1 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 1-1 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 2 is halogen, the halogen may be F, cl, br or I.
When R 2 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 3 is halogen, the halogen may be F, cl, br or I.
When R 3 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 3 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 3 is C 2-C8 oxaalkyl, said C 2-C8 oxaalkyl may be C 2-C4 oxaalkyl, for example Me-O-CH 2- CH2 -or Me-O-CH 2 -.
When R 3-1 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 4 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 4 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 4-1 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 5 is halogen, the halogen may be F, cl, br or I.
When R 5 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 5 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 6 is halogen, the halogen may be F, cl, br or I.
When R 6 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 6 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 6 is an aryl group of C 6-C12, the aryl group of C 6-C12 may be phenyl, naphthyl or phenanthryl.
When R 6 is aryl of C 6-C12 substituted with one or more R 6-1, the number of R 6-1 may be 1-3.
When R 6 is aryl of C 6-C12 substituted with one or more R 6-1, the aryl of C 6-C12 may be phenyl, naphthyl or phenanthryl.
When R 6-1 is halogen, the halogen may be F, cl, br or I.
When R 6-1 is C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl, preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl.
When R 6-1 is C 1-C8 alkoxy, the C 1-C8 alkoxy may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy or tert-butoxy.
When R 2 and R 3 together with the carbon atom between them form an aryl group of C 6-C14, the aryl group of C 6-C14 may be phenyl or naphthyl.
When R 2 and R 3 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 23-1, the number of R 23-1 can be 1-3.
When R 2 and R 3 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 23-1, the aryl group of C 6-C14 may be phenyl, naphthyl or phenanthryl, e.g
When R 2 and R 3 together with the carbon atom therebetween form a 5-10 membered heteroaryl group, the 5-10 membered heteroaryl group may be a benzofuranyl group, for example
When R 23-1 and R 23-2 are independently halogen, the halogen may be F, cl, br or I.
When R 23-1 and R 23-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl; preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl; methyl is more preferred.
When R 23-1 and R 23-2 are independently C 1-C8 alkoxy, the alkoxy group of C 1-C8 may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy, tert-butoxy.
When R 1、R2 and R 3 together with the carbon atom therebetween form a C 10-C14 aryl group, said C 10-C14 aryl group may be a C 10-C12 aryl group, e.g
When R 1、R2 and R 3 together with the carbon atom therebetween form a C 6-C10 aryl-C 3-C7 cycloalkenyl, said C 6-10 aryl-C 3-7 cycloalkenyl can be C 6-10 aryl-C 5-6 cycloalkenyl, preferably 1H-phenalkenyl, benzocyclopentenyl or fluorenyl, e.g.
When R 4 and R 5 together with the carbon atom therebetween form a C 5-C8 cycloalkenyl group, said C 5-C8 cycloalkenyl group may be a cyclopentenyl group or a cyclohexenyl group, e.g
When R 4 and R 5 together with the carbon atom therebetween form an aryl group of C 6-C14, the aryl group of C 6-C14 may be phenyl, naphthyl or phenanthryl, e.g
When R 4 and R 5 together with the carbon atoms in between form an aryl group of C 6-C14 substituted by one or more R 45-1, the number of R 45-1 is 1-3.
When R 4 and R 5 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 45-1, the aryl group of C 6-C14 may be phenyl, naphthyl or phenanthryl, e.g
When R 4 and R 5 together with the carbon atom therebetween form a 5-to 10-membered heteroaryl group, the 5-to 10-membered heteroaryl group may be furyl, pyrrolyl, thienyl, pyranyl or pyridyl, preferably furyl, thienyl or pyrrolyl, for example
When R 4 and R 5 together with the carbon atoms therebetween form a 5-to 10-membered heteroaryl group substituted with one or more R 45-2, the number of R 45-2 is 1-3.
When R 4 and R 5 together with the carbon atom therebetween form a 5-to 10-membered heteroaryl group substituted with one or more R 45-2, the 5-to 10-membered heteroaryl group may be furyl, pyrrolyl, thienyl, pyranyl or pyridyl, and may be furyl, thienyl or pyrrolyl, for example
When R 45-1 and R 45-2 are independently halogen, the halogen may be F, cl, br or I.
When R 45-1 and R 45-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl may be C 1-C4 alkyl; preferably methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl; methyl is more preferred.
When R 45-1 and R 45-2 are independently C 1-C8 alkoxy, the alkoxy of C 1-C8 may be C 1-C4 alkoxy, preferably methoxy, ethoxy, isopropoxy, tert-butoxy.
In some embodiments of the application, certain groups in compound 1 are defined as follows (groups not mentioned are as described in any embodiment of the application).
X is Br or I;
R 1 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8 or aryl of C 6-C12;
r 2 is hydrogen or halogen;
R 3 is halogen, C 1-C8 alkyl, C 1-C8 alkoxy, C 2-C8 oxaalkyl or
R 3-1 is C 1-C8 alkyl;
r 4 is C 1-C8 alkyl, C 1-C8 alkoxy or
R 5 is hydrogen or halogen;
R 6 is hydrogen or alkyl of C 1-C8;
Or R 2 and R 3 together with the carbon atom between them form a C 6-C14 aryl or 5-10 membered heteroaryl;
Or R 1、R2 and R 3 together with the carbon atom therebetween form an aryl group of C 10-C14 or an aryl group of C 6-C10 and cycloalkenyl group of C 3-C7;
Or R 4 and R 5 together with the carbon atom in between form a C 5-C8 cycloalkenyl, a C 6-C14 aryl or a 5-to 10-membered heteroaryl.
In some embodiments of the invention, X is Br or I.
In some embodiments of the invention, R 1 is H, halogen, methyl, methoxy, or phenyl.
In some embodiments of the invention, R 2 is H or halogen.
In some embodiments of the invention, R 3 is halogen, methyl, ethyl, methoxy, CH 3OCH2 -or EtO 2 C-.
In some embodiments of the invention, R 4 is methyl, methoxy, or
In some embodiments of the invention, R 5 is H or halogen.
In some embodiments of the invention, R 6 is H or methyl.
In some embodiments of the invention, R 2 and R 3 together with the carbon atoms therebetween form a phenyl group (e.g) Or benzofuranyl (e.g)。
In some embodiments of the invention, R 1、R2 and R 3 together with the carbon atom therebetween form a 1H-phenalkenyl group (e.g) Benzocyclopentenyl (e.g) Or fluorenyl (e.g)。
In some embodiments of the invention, R 4 and R 5 together with the carbon atom therebetween form a cyclohexenyl group, e.g
In some embodiments of the invention, R 4 and R 5 together with the carbon atoms therebetween form a phenyl, naphthyl or phenanthryl group, e.g
In some embodiments of the invention, R 4 and R 5 together with the carbon atoms therebetween form a furyl group, e.gIn some embodiments of the invention, fragments of a compound of formula IIs that
In some embodiments of the invention, fragments of a compound of formula IIs that
In some embodiments of the invention, the compound of formula I may be any one of the following structures:
in some embodiments of the invention, compound 3 may be any one of the following structures or an enantiomer thereof:
the rhodium catalyst is a conventional rhodium catalyst for C-H bond activation reaction in the field.
In some embodiments of the invention, the rhodium catalyst is preferably a monovalent rhodium catalyst and/or a trivalent rhodium catalyst, more preferably a trivalent rhodium catalyst.
In some embodiments of the invention, when the rhodium catalyst is a trivalent rhodium catalyst, the trivalent rhodium catalyst may be a chiral cyclopentadienyl rhodium (III) complex conventional in the art, preferably Wherein R 8 and R 8' are independently H, C 1-C8 alkyl, substituted or unsubstituted C 3-C8 cycloalkyl, or C 6-C12 aryl; r 9 and R 9' are independently H, C 1-C8 alkyl; r 10 and R 10' are independently H, C 1-C8 alkyl, C 1-C8 alkoxy, C 6-C12 aryl or C 6-C12 arylbenzyloxy.
In some embodiments of the invention, when the rhodium catalyst is a monovalent rhodium catalyst, the monovalent rhodium catalyst may be a chiral cyclopentadienyl rhodium (I) complex conventional in the art, preferablyOr an enantiomer thereof.
In some embodiments of the invention, the rhodium catalyst is selected from any one of the following structures:
in some embodiments of the invention, when the chiral catalyst is When compound 3 is in S configuration; when the chiral catalyst isOr (b)Compound 3 is in the R configuration.
In some embodiments of the invention, when chiral catalysts C1-C8 are S-type, compound 3 is in the S configuration; when the chiral catalyst C9-C32 is in R type, the compound 3 is in S configuration.
In some embodiments of the invention, when chiral catalyst C1'-C8' is R-type, compound 3 is in the R configuration; when the chiral catalyst C9 '-C32' is in an S type, the compound 3 is in an R configuration.
The silver salt is conventional silver salt for C-H bond activation reaction in the field.
In some embodiments of the invention, the silver salt is a silver salt conventional in the art, preferably one or more of AgSbF 6、AgF、AgNTf2、AgOTf、 AgOAc、Ag2CO3、AgBF4、AgNO3 and i PrCOOAg, more preferably one or more of AgSbF 6、AgF、AgNTf2、 AgOTf、AgBF4 and AgNO 3; even more preferred is AgNO 3.
The copper salt is copper salt which is conventional in the C-H bond activation reaction in the field.
In some embodiments of the invention, the copper salt is preferably a divalent copper salt.
In some embodiments of the invention, the divalent copper salt may be CuBr 2 and/or Cu (OAc) 2; cu (OAc) 2 is preferred.
The organic solvent is a conventional organic solvent for C-H bond activation reaction in the field.
In some embodiments of the invention, the organic solvent may be one or more of an alcoholic solvent (e.g., one or more of methanol, hexafluoroisopropanol, and t-amyl alcohol), a halogenated hydrocarbon solvent (e.g., dichloromethane and/or dichloroethane), an ether solvent (e.g., 1, 4-dioxane and/or tetrahydrofuran), a benzene solvent (e.g., toluene), a nitrile solvent (e.g., acetonitrile), and an amide solvent (e.g., N-dimethylformamide); preferably a nitrile solvent (e.g., acetonitrile) and/or an amide solvent (e.g., N-dimethylformamide).
In some embodiments of the present invention, the molar concentration of the compound of formula I is conventional in the art, preferably 0.01 to 0.5mol/L, more preferably 0.05 to 0.2mol/L.
In some embodiments of the invention, the molar ratio of the rhodium catalyst to the compound of formula I is conventional in the art, preferably from 0.01 to 0.2:1, more preferably from 0.02 to 0.1:1.
In some embodiments of the invention, the molar ratio of the silver salt to the compound of formula I is conventional in the art, preferably from 0.02 to 0.8:1, more preferably from 0.04 to 0.4:1.
In some embodiments of the invention, the molar ratio of the copper salt to the compound of formula I is conventional in the art, preferably 1-5:1, more preferably 1-3:1.
The reaction is preferably carried out under a protective gas atmosphere, for example under an inert gas atmosphere.
In some embodiments of the present invention, the shielding gas is one or more of helium, neon, nitrogen and argon, and more preferably argon.
The temperature of the halogenation reaction is the reaction temperature conventional in the art of C-H bond activation reaction.
In some embodiments of the invention, the halogenation reaction is carried out at a temperature of from 0 to 100deg.C, preferably from 25 to 80deg.C.
The halogenation reaction time is a reaction time conventional in the art of C-H bond activation reactions.
In some embodiments of the invention, the halogenation reaction is carried out for a reaction time of from 0.5 to 24 hours, preferably from 1 to 15 hours, and more preferably from 2 to 12 hours.
In some embodiments of the invention, the halogenation reaction may also incorporate additives, which may be one or more of NaOAc, naOTf, pivOCs, pivOH and 4-CF 3 PhCOOH, preferably NaOTf and/or 4-CF 3 PhCOOH.
In some schemes of the invention, in the presence of rhodium catalyst, silver salt and copper salt in an organic solvent under the atmosphere of protective gas, the compound shown as the formula I and the compound shown as the formula II undergo halogenation; the organic solvent is a nitrile solvent; the chiral rhodium catalyst isThe silver salt is one or more of AgSbF 6、AgF、AgNTf2、AgOTf、 AgOAc、Ag2CO3、AgBF4、AgNO3 and i PrCOOAg; the copper salt is Cu (OAc) 2; the molar concentration of the compound shown as the formula 1 in the organic solvent is 0.05-0.2mol/L; the molar ratio of the rhodium catalyst to the compound shown as the formula 1 is 0.02-0.1:1; the molar ratio of the silver salt to the compound shown in the formula 1 is 0.04-0.4:1; the mol ratio of the copper salt to the compound shown in the formula 1 is 1-3:1; wherein each R 8 is independently H, C 1-C8 alkyl, substituted or unsubstituted C 3-C8 cycloalkyl, or substituted or unsubstituted C 6-C12 aryl; each R 9 is independently H, C 1-C8 alkyl; r 10 is each independently H, C 1-C8 alkyl, C 1-C8 alkoxy, substituted or unsubstituted C 6-C12 aryl, substituted or unsubstituted C 6-C12 arylbenzyloxy.
In some embodiments of the invention, the progress of the halogenation reaction can be monitored using methods conventional in the art (e.g., TLC, HPLC, GC or NMR), typically by taking the compound of formula I as the end point of the reaction when it is no longer reacting.
In some embodiments of the present invention, the halogenation reaction is preferably completed and further comprises post-treatment operations. The post-treatment operations and methods may be conventional in the art of post-reaction treatment, and preferably include the steps of: quenching, extracting, separating and purifying. The quenching operation and method may be conventional in the art for such reactions, and the quenching solvent is preferably water. The extraction operation and method can be those conventional in the art for such reactions, and the solvent for extraction is preferably methylene chloride. The separation and purification procedure and method may be those conventional in the art, preferably column chromatography, and the developing solvent system for column chromatography may be those conventional in the art, preferably alkane solvent/ester solvent/Et 3 N (e.g., petroleum ether/ethyl acetate/Et 3 N), more preferably alkane solvent/ester solvent/Et 3 n=1/10/0.01.
The invention provides a rhodium complex shown in a formula IV or an enantiomer thereof,
The present invention also provides the use of a rhodium complex or enantiomer thereof as described above in formula IV as a catalyst in a reaction, preferably in a halogenation reaction; more preferred is the use as a catalyst in asymmetric halogenation reactions, such as halogenation reactions as described above.
The present invention also provides a catalyst composition comprising a silver salt as described above, said copper salt and a rhodium complex as described above and shown in formula IV.
In some embodiments of the invention, the molar ratio of rhodium complex as described above in formula IV to the silver salt is conventional in the art, preferably 1: (1-10), further preferably 1:2, 1:4, 1:6 or 1:8.
In some embodiments of the invention, the molar ratio of rhodium complex of formula IV to copper salt described above is conventional in the art, preferably 1: (20-100), further preferably 1:20, 1:40, 1:60 or 1:80.
The invention also provides the application of the catalyst composition in asymmetric catalytic reaction.
In some embodiments of the invention, the use is in the preparation of an axial chiral halobiaryl compound; for example, the reaction conditions and operation in the application are as described above for the preparation of compound 3.
The present invention also provides an axial chiral halobiaryl compound selected from any one of the following structures or enantiomers thereof:
the invention also provides an application of the axial chiral halogenated biaryl compound as an intermediate in synthesizing axial chiral phosphorus-nitrogen ligands.
The invention also provides a compound shown as a formula V or an enantiomer thereof,
The invention also provides a preparation method of the compound VII, which comprises the following steps: in the presence of palladium catalyst, compound of formula V and alkali in a solvent under the atmosphere of protective gas, the compound of formula VI and aniline undergo Buchwald-Hartwig reaction to obtain compound VII,
In one embodiment of the invention, the palladium catalyst is Pd (dba) 2.
In one embodiment of the invention, the base is t BuONa.
In one embodiment of the present invention, the solvent is toluene.
In one embodiment of the present invention, the shielding gas is argon.
The invention also provides an application of the compound shown in the formula V or an enantiomer thereof as a chiral ligand in asymmetric catalytic reaction. The application is to prepare an axial chiral compound; for example, the preparation of a compound of formula VII.
In some embodiments of the invention, the use is as a ligand in a Buchwald-Hartwig reaction of a compound of formula V or an enantiomer thereof.
Unless otherwise indicated, the terms used in the present invention have the following meanings:
In this specification, groups and substituents thereof can be selected by one skilled in the art to provide stable moieties and compounds. When substituents are described by conventional formulas written from left to right, the substituents also include chemically equivalent substituents obtained when writing formulas from right to left.
The term halogenation reaction is defined herein as a reaction that replaces a hydrogen in a hydrocarbon bond in a compound with a halogen, where the hydrocarbon bond includes, but is not limited to, sp carbon hydrogen bonds (e.g.) Sp 2 carbon-hydrogen bonds (e.g) Or sp 3 hydrocarbon bond)。
Certain chemical groups defined herein are preceded by a simplified symbol to indicate the total number of carbon atoms present in the group. For example, C 1-C6 alkyl refers to an alkyl group as defined below having a total of 1, 2, 3,4, 5 or 6 carbon atoms. The total number of carbon atoms in the reduced notation does not include carbon that may be present in a substituent of the group.
In this context, a numerical range as defined in substituents, such as 0 to 4, 1-4, 1 to 3, etc., indicates an integer within the range, such as 1-6 is 1, 2, 3, 4, 5, 6.
In addition to the foregoing, when used in the specification and claims of the present application, the following terms have the meanings indicated below, unless otherwise specified.
The term "one(s)" or "one(s) or two or more" means 1, 2, 3, 4, 5, 6, 7, 8, 9 or more.
The term "comprising" is an open-ended expression, i.e. including what is indicated by the invention, but not excluding other aspects.
The term "substituted" refers to any one or more hydrogen atoms on a particular atom being substituted with a substituent, including heavy hydrogen and variants of hydrogen, so long as the valence of the particular atom is normal and the substituted compound is stable.
In general, the term "substituted" means that one or more hydrogen atoms in a given structure are replaced with a specific substituent. Further, when the group is substituted with 1 or more of the substituents, the substituents are independent of each other, that is, the 1 or more substituents may be different from each other or the same. Unless otherwise indicated, a substituent group may be substituted at each substitutable position of the substituted group. When more than one position in a given formula can be substituted with one or more substituents selected from a particular group, then the substituents may be the same or different at each position.
In the various parts of the present specification, substituents of the presently disclosed compounds are disclosed in terms of the type or scope of groups. It is specifically noted that the present invention includes each individual subcombination of the individual members of these group classes and ranges. The term "C x-Cy alkyl" refers to straight or branched chain saturated hydrocarbons containing from x to y carbon atoms. For example, the term "C 1～C6 alkyl" or "C 1-6 alkyl" refers specifically to independently disclosed methyl, ethyl, C 3 alkyl, C 4 alkyl, C 5 alkyl, and C 6 alkyl; "C 1-4 alkyl" refers to the independently disclosed methyl, ethyl, C 3 alkyl (i.e., propyl, including n-propyl and isopropyl), C 4 alkyl (i.e., butyl, including n-butyl, isobutyl, sec-butyl, and tert-butyl).
The term "halogen" is selected from F, cl, br or I.
The term "alkoxy" refers to the group-O-R X, wherein R X is alkyl as defined above.
The terms "moiety", "structural moiety", "chemical moiety", "group", "chemical group" as used herein refer to a particular fragment or functional group in a molecule. Chemical moieties are generally considered to be chemical entities that are embedded or attached to a molecule.
When none of the listed substituents indicates through which atom it is attached to a compound included in the chemical structural formula but not specifically mentioned, such substituents may be bonded through any of their atoms. Combinations of substituents and/or variants thereof are permissible only if such combinations result in stable compounds.
Where no substituent is explicitly indicated in a recited group, such a group is merely unsubstituted. For example, when "C 1～C4 alkyl" has no previous definition of "substituted or unsubstituted", only "C 1～C4 alkyl" itself or "unsubstituted C 1～C4 alkyl".
In the present application, as part of a group or other groups (e.g., as used in halogen-substituted alkyl groups and the like), the term "alkyl" is meant to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the indicated number of carbon atoms; such as straight or branched saturated hydrocarbon chains containing 1 to 16 carbon atoms; also for example, alkyl of C 1-C6. As defined in "C 1～C6 alkyl" is inclusive of groups having 1,2, 3, 4, 5, or 6 carbon atoms in either a straight or branched chain structure. Wherein propyl is C 3 alkyl (including isomers such as n-propyl or isopropyl); butyl is C 4 alkyl (including isomers such as n-butyl, sec-butyl, isobutyl, or tert-butyl); pentyl is C 5 alkyl (including isomers such as n-pentyl, 1-methyl-butyl, 1-ethyl-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, isopentyl, t-pentyl or neopentyl); hexyl is C 6 alkyl (including isomers such as n-hexyl, 1-ethyl-2-methylpropyl, 1, 2-trimethylpropyl, 1-dimethylbutyl, 1, 2-dimethylbutyl, 2-dimethylbutyl, 1, 3-dimethylbutyl, 2-ethylbutyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 2, 3-dimethylbutyl).
In the present application, the term "cycloalkenyl", by itself or as part of another substituent, refers to an unsaturated, non-aromatic group containing a double bond. A monocyclic, polycyclic or bridged carbocyclic substituent containing a partially unsaturated double bond, and which may be attached to the remainder of the molecule by a single bond via any suitable carbon atom; when polycyclic, it may be a bridged or spiro ring system with a parallel or spiro ring connection (i.e., two geminal hydrogens on carbon atoms are replaced with alkylene groups). In some embodiments, a "cycloalkenyl" is preferably a non-aromatic group containing one double bond, having 3-7 ring carbon atoms, more preferably 3-6 carbon atoms, such as cyclopropenyl, cyclobutenyl, cyclopentenyl or cyclohexenyl. In some embodiments, a "cycloalkenyl" is a monocyclic, unsaturated, carbocycloalkenyl group having 5 to 6 ring atoms ("5-6 membered cycloalkenyl").
The term "oxaalkyl" refers to an alkyl group in which carbon in the alkyl group has been replaced with oxygen, wherein the number of carbon in the oxygen-replaced alkyl group is not less than 1.
The term "heterocycloalkyl" refers to a saturated monocyclic group having heteroatoms, preferably a 3-7 membered saturated monocyclic ring containing 1, 2 or 3 ring heteroatoms independently selected from N, O and S. Examples of heterocycloalkyl groups are: pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, tetrahydrothienyl, tetrahydropyridinyl, azetidinyl, thiazolidinyl, oxazolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, piperazinyl, azepanyl, diazepinyl, oxaazepanyl, dioxolanyl, dioxanyl, and the like. Preferred heterocyclyl groups are 1, 3-dioxolanyl, 1, 4-dioxane.
The term "aryl" refers to a fully carbon aromatic group having a fully conjugated pi-electron system of the specified number of carbon atoms (e.g., when bicyclic or tricyclic, each ring meeting the shock rule) which may be a monocyclic or fused ring, typically having 6 to 20 carbon atoms, preferably having 6 to 14 carbon atoms, and most preferably having 6 carbon atoms. Examples of aryl groups include, but are not limited to: monocyclic aryl groups such as C 6 aryl (phenyl), bicyclic aryl groups such as C 10 aryl (naphthyl), tricyclic aryl groups such as C 14 aryl (phenanthryl and anthracyl).
The term "arylocycloalkenyl" refers to a group formed by the condensation of an aryl group and a cycloalkenyl group, wherein "aryl" and "cycloalkenyl" are as previously described, examples of "arylocycloalkenyl" are
The term "heteroaryl" refers to an aromatic group containing heteroatoms, which may be a single ring or a fused ring, preferably containing 1 to 4 5-12 membered heteroaryl groups independently selected from N, O and S, including, but not limited to, pyrrolyl, furanyl, thienyl, indolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinolinyl, isoquinolinyl, (benzoxazolyl, (benzo) furanyl, (benzo) thienyl, (benzo) thiazolyl, triazolyl. In one embodiment, a 5-6 membered monocyclic heteroaryl group typically containing 1 or more heteroatoms independently selected from N, O and S. In one embodiment, a "heteroaryl" is a 5-6 membered heteroaryl, wherein the heteroatom is selected from one or more of N, O and S, and the number of heteroatoms is 1,2, or 3.
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: the invention provides a preparation method of a novel axial chiral halogenated biaryl compound. The preparation method can be used for synthesizing the axial chiral halogenated biaryl compound with single configuration, and has the advantages of easily available raw materials, better substrate universality, high enantioselectivity, high reaction yield, high reaction efficiency and the like.
Drawings
FIG. 1 is a thermal ellipsometry of compound I-1 as measured by single crystal X-ray diffraction.
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.
Example 1: synthesis of substrates in the present invention
The synthesis of the substrate is carried out according to known literature, synthesis procedure reference (Zheng, j.; you, s. -l.angelw.chem.int. Ed.2014,53,13244.)
The experimental steps are as follows: in a 100mL two-port flask were added 1-chloroisoquinoline derivative (10 mmol) and Pd (PPh 3)4 (346.7 mg, 0.3 mmol) and DME (25 mL.) followed by aqueous Na 2CO3 (2.1 g,20 mmol) and boric acid (11 mmol) in methanol (8 mL.) the reaction mixture was stirred at 80℃overnight.
HRMS (ESI) calculated C 23H15BrN[M+H]+: 383.0310. Found 383.0310.
HRMS (ESI) calculated C 19H13ClN[M+H]+: 289.0658. Found 289.0658.
HRMS (ESI) calculated C 19H13BrN[M+H]+: 333.0153. Found 333.0153.
HRMS (ESI) calculated C 25H18N[M+H]+: 331.1361. Found 331.1361.
HRMS (ESI) calculated C 17H12NO[M+H]+: m= 245.0841. Found m= 245.0841.
HRMS (ESI) calculated C 21H14NO[M+H]+: 295.0997. Found 295.0997.
HRMS (ESI) calculated C 17H16NO[M+H]+: 249.1154. Found 249.1154.
HRMS (ESI) calculated C 18H16NO2[M+H]+: 277.1103. Found 277.1103.
HRMS (ESI) calculated C 18H16NO2[M+H]+: 277.1103. Found 277.1103.
Example 2: the chiral rhodium catalyst is synthesized by the following steps: synthesis of (S) -C8 catalysts
Compound 9
The experimental steps are as follows: to a dry Schlenk flask was added compound 8 (4 mmol), cyclohexanone (40 mmol) and tetrahydropyrrole (40 mmol), and vacuum was applied and THF (10 mL) and MeOH (10 mL) were added under argon atmosphere. The reaction was carried out at room temperature. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator, and the residue was separated by silica gel column chromatography (PE) to give the corresponding product 9.
(90% Yield), analytical data: melting point = 153.3-155.0 ℃.(C=0.5, chloroform ).1H NMR (400MHz,CD2Cl2)δ7.11(d,J＝4.8Hz,1H),6.93(t,J＝4.4Hz,1H),6.23(d,J＝1.2Hz,1H),3.49(d,J＝ 13.6Hz,1H),3.32(d,J＝13.6Hz,1H),3.07-2.99(m,1H),2.89(dd,J＝15.6,8.4Hz,1H),2.55(t,J＝5.8Hz,2H),2.32(dd,J＝12.4,6.8Hz,1H),2.02-1.94(m,1H),1.73-1.62(m,3H).13C NMR(100MHz,CDCl3) δ154.0,147.9,145.7,143.8,137.2,135.9,129.5,127.8,123.2,117.1,61.8,39.0,33.6,32.5,30.8,29.9,29.2,27.1,23.2,14.5.IR( film ):νmax(cm-1)＝2926,2850,1709,1635,1593,1433,1346,1249,1166,1127,1024, 940,831,796,757,679.HRMS(ESI) calculated C 30H30[M]+: 390.2342, found 390.2346.
Compound 10
The experimental steps are as follows: to a dry Schlenk flask was added compound 9 (2.3 mmol), which was evacuated and diethyl ether (20 mL) was added under argon. The temperature was reduced to-78℃and MeLi (6.9 mmol) was added at-78 ℃. After the reaction was completed, the reaction was quenched with water in an ice bath, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator and the residue was separated by silica gel column chromatography (PE) to give the corresponding product 10.
(64% Yield), analytical data: white solid melting point = 105.2-106.8 ℃.(C=0.5, chloroform ).1H NMR (400MHz,CDCl3)δ7.18-7.09(m,6.9H),6.99-6.85(m,3.9H),6.06-6.03(m,1.4H)*,5.97(s,1H),3.51-3.29 (m,6H),3.21(d,J＝14.0Hz,1.2H),3.13(d,J＝14.0Hz,1.2H),3.07-2.96(m,5.4H),2.94-2.86(m,5.2H), 2.80(d,J＝14.8Hz,1.6H),2.37-2.28(m,4H),2.06-1.94(m,4.2H),1.69-1.64(m,2.3H),1.48-1.35(m,10.4H),1.27(s,2.1H)*,1.05(s,3H).13C NMR(101MHz,CDCl3)δ154.1,147.5,147.5 147.4,147.3,146.0,145.9, 143.2,143.1,142.8,142.7,139.1,137.4,136.0,135.5,134.3,134.1,130.6,130.5,130.5,129.2,129.1,128.8,128.5,127.7,127.6,127.4,127.3,122.7,122.7,122.2,122.1,61.3,61.1,45.6,38.9,38.8,38.5,38.5,38.3, 38.2,37.7,37.5,36.4,36.3,32.2,32.1,30.7,30.6,30.6,30.5,30.2,30.2,26.6,26.5,22.8,22.7,22.3,22.3.IR( film ):νmax(cm-1)＝2921,2847,1712,1591,1466,1446,1371,1259,1203,1073,1048,960,871,797,755, 680.HRMS(ESI) calculated C 31H34[M]+: 406.2655, found 406.2670.
Compound 11
The experimental steps are as follows: to a dry Schlenk flask was added compound 10 (1.1 mmol), [ Rh (cod) OAc ] 2 (0.66 mmol), and vacuum was applied and toluene (7 mL) and methanol (7 mL) were added under an argon atmosphere. The reaction was carried out at 70 ℃. After the reaction was completed, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator, and the residue was separated by silica gel column chromatography (toluene) to give the corresponding product 11.
(71% Yield), analytical data: melting point = 196.4-198.2 ℃.(C=0.5, chloroform ).1H NMR (400MHz,CD2Cl2)δ7.56(d,J＝7.6Hz,1H),7.30(t,J＝7.4Hz,1H),7.19-7.09(m,3H),6.94(d,J＝7.2Hz, 1H),5.02(d,J＝2.0Hz,1H),4.71(d,J＝2.0Hz,1H),3.89(t,J＝7.6Hz,2H),3.42(d,J＝14.0,1H),3.25(d,J＝14.0Hz,1H),3.13(d,J＝12.8Hz,1H),3.12-3.05(m,2H),3.03-2.97(m,2H),2.89(dd,J＝16.0,8.8 Hz,2H),2.66(d,J＝13.2Hz,1H),2.44-2.36(m,2H),2.29-2.21(m,2H),2.10-1.86(m,6H),1.71-1.43(m,12H),1.18(s,3H).13C NMR(100MHz,CD2Cl2)δ147.9,147.1,143.6,142.5,137.7,135.6,131.7,128.2, 128.0,127.9,123.0,122.8,118.7(d,J＝5Hz),108.0(d,J＝4Hz),99.2(d,J＝5Hz),86.4(d,J＝4Hz),84.3 (d,J＝4Hz),66.5,66.4,63.7,63.6,61.8,39.8,39.5,39.3,38.7,34.5,33.9,31.0,30.8,30.4,30.3,28.5,26.9,24.8,23.1,22.9.IR( film ):νmax(cm-1)＝2921,2854,2822,1592,1466,1444,1428,1372,1321,1259,1154, 956,894,863,801,754,647.HRMS(AP-MALDI) calculated C 35H45Rh[M]+: 616.2571, found 616.2567.
Catalyst (S) -C8
The experimental steps are as follows: to a dry Schlenk flask was added compound 11 (1 mmol), I 2 (2 mmol), and toluene (10 mL) under argon. The reaction was carried out at room temperature. After the completion of the reaction, toluene was removed under reduced pressure by a rotary evaporator, and the residue was washed with petroleum ether to give the corresponding product (S) -C8.
(88% Yield), analytical data: reddish brown solid melting point = 334.1-335.7 ℃.(C=0.5, chloroform ).1H NMR (400MHz,CD2Cl2)δ7.66(d,J＝7.6Hz,1H),7.22(d,J＝7.6Hz,1H),7.17-7.15(m,2H),7.01-6.94(m,2H), 5.73(s,1H),5.38(s,1H),3.92(d,J＝13.2Hz,1H),3.53(d,J＝13.2Hz,1H),3.13(s,2H),3.06(dd,J＝10.4, 4.0Hz,2H),3.03-2.98(m,1H),2.87(dd,J＝16.0,8.4Hz,1H),2.34-2.24(m,2H),2.03-1.89(m,2H),1.71(d,J＝12.4Hz,1H),1.61-1.41(m,10H),1.30(s,3H).13C NMR(100MHz,CD2Cl2)δ147.8,147.0,144.3, 142.8,134.1,133.3,131.0,129.1,128.3,128.1,124.8,124.2,113.3(d,J＝6Hz),106.4(d,J＝6Hz),96.5(d, J＝9Hz),87.1(d,J＝6Hz),79.8(d,J＝5Hz),61.9,39.9,39.0,38.1,34.3,30.6,30.4,30.3,30.1,28.5,26.1,24.8,22.6,22.3.IR( film ):νmax(cm-1)＝2923,2851,1720,1593,1467,1446,1260,1100,1018,918,801, 756,694.HRMS(AP-MALDI) calculated C 62H66I3Rh2[M-I]+: 1397.0403, found 1397.0393.
Example 3: effect of solvent Effect on rhodium catalyzed C-H halogenation reactions a
Example 4: influence of chiral rhodium catalyst on rhodium-catalyzed C-H halogenation a,b
Example 5 influence of silver salts on rhodium-catalyzed C-H halogenation a
EXAMPLE 6 Effect of copper salt on rhodium catalyzed C-H halogenation a
Example 7: effect of concentration effects on rhodium catalyzed C-H halogenation reactions a
Example 8 influence of temperature on rhodium-catalyzed C-H halogenation a
Example 9 Effect of additives on rhodium catalyzed C-H halogenation a
Example 10 control experiment a
Example 11: asymmetric synthesis of axial chiral halobiaryl 3
To a dry Schlenk flask was added compound 1 (61.0 mg,0.2 mmol), compound 2 (90.0 mg,0.4 mmol), C8 (7.8 mg,0.005 mmol), agNO 3 (6.8 mg,0.04 mmol) and Cu (OAc) 2 (0.4 mmol), evacuated, and acetonitrile (2 mL) was added under an argon atmosphere. Heating to 40 ℃ to react. After the completion of the reaction, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator, and the residue was separated by column chromatography on silica gel (PE/EA/Et 3 n=20/1/0.01) to give the corresponding product.
Example 12
(84.6 Mg,98% yield,94% ee): yellow solid, melting point 190.0-192.0 ℃, [ α ] D 21 = +71.5 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.89(d,J＝4.8Hz,1H),8.03(d,J＝8.4Hz,1H),7.97(d,J＝8.8 Hz,1H),7.91(d,J＝8.4Hz,1H),7.88-7.83(m,2H),7.81(d,J＝8.4Hz,1H),7.73(d,J＝8.8Hz,1H),7.53-7.39(m,3H),7.20(t,J＝7.2Hz,1H),7.14(d,J＝8.8Hz,1H),7.11-7.02(m,1H).13C NMR(100MHz, CDCl3)δ159.2,145.7,144.4,138.2,136.1,133.5,133.2,132.9,132.6,129.8,129.2,129.1,128.3,127.7, 127.5,127.1,126.8,126.2,125.9,125.7,125.2,122.0,96.6.IR( thin film ):νmax(cm-1)＝1612,1581,1554,1500, 1421,1363,1298,1236,1101,857,833,806,781,744,680,515;HRMS(ESI) calculated C 23H14NI[M+H]+: 432.0249. Found: 432.0242. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.15 min, t (minor) =14.67 min.
The single crystal growth method comprises dissolving I-1 (50 mg) in 1mL of dichloromethane, adding 2mL of petroleum ether, standing, and volatilizing slowly. The I-1 single crystal data are shown below, and the thermal ellipsoids are shown in FIG. 1.
The following compounds of examples 13-32, examples 34-47 were prepared as described in reference to example 12.
Example 13
(82.6 Mg,93% yield,91% ee): yellow solid, melting point 163.7-165.8 ℃, [ α ] D 28 = +62.9 (c=0.2 chloroform ,91％ee).1H NMR(400MHz,CDCl3)δ8.87(d,J＝5.2Hz,1H),8.05(d,J＝8.4Hz,1H),7.98-7.89(m, 2H),7.87-7.81(m,2H),7.79(d,J＝8.4Hz,1H),7.55(d,J＝8.8Hz,1H),7.52-7.46(m,1H),7.45-7.39(m,1H),7.22-7.13(m,2H),7.11-7.04(m,1H),2.77(s,3H).13C NMR(100MHz,CDCl3)δ159.4,144.4, 144.2,138.2,136.5,136.4,133.2,132.9,132.8,132.5,129.2,129.1,127.7,127.1,127.1,126.9,126.5,125.9,125.8,125.4,124.7,121.9,96.5,19.2.IR( thin film ):νmax(cm-1)＝2920,1607,1581,1554,1507,1419,1358, 1300,1236,1156,1031,990,904,869,853,821,752,726,679,645,606,538,502;HRMS(ESI) calculated C 24H16NI[M+H]+: 446.0406. Found: 446.0407. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.95 min, t (minor) =18.80 min.
Example 14
(71.7 Mg,78% yield,95% ee): yellow solid, melting point 174.4-176.2 ℃, [ α ] D 25 = +121.6 (c=0.2 chloroform ,95％ee).1H NMR(400MHz,CDCl3)δ8.95-8.77(m,1H),8.33(d,J＝8.8Hz,1H),7.96(d,J＝9.2 Hz,1H),7.89-7.82(m,2H),7.82-7.77(m,1H),7.60(d,J＝8.4Hz,1H),7.51-7.40(m,2H),7.36(s,1H),7.23-7.18(m,1H),7.16-7.04(m,2H),4.08(s,3H).13C NMR(100MHz,CDCl3)δ159.4,155.5,144.4, 138.4,138.3,133.2,132.5,129.3,129.1,128.0,127.7,127.0,126.0,125.9,125.9,125.8,125.6,122.5,121.9,114.5,96.1,56.1.IR( thin film ):νmax(cm-1)＝2935,1610,1577,1506,1458,1415,1359,1301,1243,1228,1160, 1101,989,902,869,854,832,820,745,679,663,615,592,538,510;HRMS(ESI) calculated C 24H16ONI [M+H]+: 462.0355. Found: 462.0348. Chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =7.42 min, t (minor) =13.53 min.
Example 15
(86.7 Mg,97% yield,94% ee): yellow solid, melting point 89.8-91.6 ℃, [ α ] D 21 = +73.6 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.87(d,J＝5.2Hz,1H),8.18(d,J＝8.4Hz,1H),7.97(d,J＝8.8 Hz,1H),7.92-7.83(m,2H),7.81(d,J＝8.8Hz,1H),7.76(d,J＝9.6Hz,1H),7.52(t,J＝7.6Hz,1H),7.49-7.40(m,2H),7.30-7.24(m,1H),7.19-7.04(m,2H).13C NMR(100MHz,CDCl3)δ158.4,157.8(d,J＝ 256.5Hz),144.3,142.0(d,J＝4.9Hz),138.3,133.5(d,J＝4.9Hz),133.2,132.7,129.2,129.0,128.5,127.7,127.2,127.0(d,J＝1.9Hz),126.2(d,J＝2.7Hz),125.8,125.5,125.4,124.0(d,J＝16.2Hz),122.2,121.1(d, J＝5.1Hz),120.0(d,J＝22.5Hz),94.1(d,J＝8.8Hz).IR( thin film ):νmax(cm-1)＝1619,1589,1554,1504,1415, 1359,1301,1241,1219,1155,1060,991,852,820,748,680,605,566,539,503;HRMS(ESI) calculated C 23H13NFI[M+H]+: 450.0155, found: 450.0145 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =6.39 min, t (minor) =9.85 min.
Example 16
(90.9 Mg,98% yield,88% ee): oily liquid [. Alpha. ] D 21 = +56.4 (c=0.2 chloroform ,88％ee).1H NMR (400MHz,CDCl3)δ8.86(d,J＝5.2Hz,1H),8.35(d,J＝8.4Hz,1H),8.16(s,1H),7.98(d,J＝8.8Hz,1H), 7.91-7.84(m,2H),7.81(d,J＝8.4Hz,1H),7.57(t,J＝8.0Hz,1H),7.52-7.43(m,2H),7.31-7.25(m,1H),7.19-7.09(m,2H).13C NMR(100MHz,CDCl3)δ158.3,145.1,144.3,138.4,135.6,133.5,133.3,132.8, 132.7,130.9,129.3,128.9,128.4,127.9,127.8,127.3,126.8,125.8,125.5,125.3,125.1,122.3,94.9.IR( thin film ):νmax(cm-1)＝1584,1556,1501,1448,1356,1301,1263,1238,1166,993,951,907,868,854,823,749, 729,678,596,500;HRMS(ESI) calculated C 23H13NClI[M+H]+: 465.9859. Found: 465.9859. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =7.02 min, t (minor) =11.99 min.
Example 17
(93.2 Mg,92% yield,92% ee): yellow solid melting point 108.8-110.7 ℃, [ α ] D 21 = +96.8 (c=0.2 chloroform ,92％ee).1H NMR(400MHz,CDCl3)δ8.87(d,J＝5.2Hz,1H),8.37(s,1H),8.31(d,J＝8.8Hz,1H), 7.97(d,J＝8.8Hz,1H),7.88-7.83(m,2H),7.80(d,J＝8.8Hz,1H),7.59-7.53(m,1H),7.50(d,J＝8.4Hz,1H),7.46(t,J＝7.6Hz,1H),7.28-7.22(m,1H),7.18-7.08(m,2H).13C NMR(100MHz,CDCl3)δ158.3, 145.9,144.4,138.9,138.2,133.6,133.2,132.7,132.1,129.2,128.9,128.3,128.0,127.8,127.7,127.2,126.8,125.8,125.5,125.2,123.5,122.2,95.5.IR( thin film ):νmax(cm-1)＝1610,1583,1555,1496,1419,1399,1355, 1301,1285,1262,1237,1195,1168,1137,1112,1016,991,935,868,853,821,748,719,684,671,591,527,497;HRMS(ESI) calculated C 23H13NBrI[M+H]+: 509.9354, found: 509.9351. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =7.37 min, t (minor) =13.36 min.
Example 18
(93.7 Mg,95% yield,94% ee): melting point 211.2-213.1 ℃ [ alpha ] D 26 = +81.8 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.89(d,J＝5.2Hz,1H),8.48(s,1H),7.95(d,J＝8.8Hz,1H), 7.93-7.71(m,6H),7.57(d,J＝8.8Hz,1H),7.40(s,3H),7.31(t,J＝8.0Hz,1H),7.13-6.97(m,2H).13C NMR(100MHz,CDCl3)δ158.1,145.1,143.9,139.9,138.6,138.2,138.1,137.2,133.2,132.6,130.6,129.6, 129.4,129.1,128.5,128.0,127.7,127.1,125.8,125.7,125.4,125.4,122.1,122.0,121.9,120.9,98.3.IR( thin film ):νmax(cm-1)＝1608,1581,1552,1505,1485,1441,1360,1296,1236,1116,1102,1013,991,947,867,850,832,800,774,751,700,651,625,596,510,497,425;HRMS(ESI) calculated C 29H16NI[M+H]+: 506.0406, found: 506.0405 chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =15.90 min, t (minor) =24.60 min.
Example 19
(96.9 Mg,96% yield,92% ee): yellow solid, melting point 259.0-261.1 ℃, [ α ] D 21 = -239.1 (c=0.2 chloroform ,92％ee).1H NMR(400MHz,CDCl3)δ8.93(d,J＝5.2Hz,1H),8.83(s,1H),8.19(d,J＝7.6Hz,1H), 8.12(d,J＝8.8Hz,1H),8.09-8.01(m,2H),8.00-7.93(m,2H),7.89(d,J＝5.2Hz,1H),7.85-7.79(m,2H),7.77(d,J＝9.2Hz,1H),7.41-7.31(m,2H),7.27(d,J＝8.8Hz,1H),6.91-6.81(m,1H).13C NMR (100MHz,CDCl3)δ159.5,144.4,142.3,138.3,135.3,133.3,132.8,132.6,131.2,130.8,130.3,129.3,129.2, 129.1,128.9,127.7,127.1,126.6,126.4,126.0,125.9,125.9,125.7,125.7,125.3,124.9,124.6,122.1,96.6.IR( thin film ):νmax(cm-1)＝1607,1582,1553,1524,1506,1414,1385,1367,1301,1284,1234,1217,1169,1143, 1122,1102,1050,1035,989,940,874,857,831,805,781,749,725,682,659,639,539,511,484;HRMS (ESI) calculated C 29H16NI[M+H]+: 506.0406, found: 506.0402 chiral column IC column, n-hexane/isopropanol=60/40, 1mL/min, detection wavelength=254 nm, t (major) =9.13 min, t (minor) = 36.48min.
Example 20
(93.3 Mg,99% yield,94% ee): yellow solid melting point 179.4-181.3 ℃, [ α ] D 25 = +69.6 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.91(d,J＝5.2Hz,1H),8.06(d,J＝8.8Hz,1H),7.97(d,J＝8.8 Hz,1H),7.92(d,J＝4.8Hz,1H),7.82(d,J＝8.4Hz,2H),7.67(d,J＝8.8Hz,1H),7.55-7.39(m,3H),7.25(t,J＝8.4Hz,1H),7.18-7.11(m,1H),6.80(t,J＝7.6Hz,1H),6.11(d,J＝7.6Hz,1H).13C NMR(100MHz, CDCl3)δ157.5,156.8,156.5,144.6,142.5,138.4,137.7,133.3,132.8,129.2,129.2,127.8,127.7,127.3, 125.8,125.5,124.6,124.5,123.0,123.0,122.4,121.8,113.5,111.6,90.2.IR( thin film ):νmax(cm-1)＝1608,1584, 1554,1508,1464,1446,1410,1380,1316,1295,1262,1237,1215,1193,1022,994,869,852,805,747,664, 591,509;HRMS(ESI) calculated C 25H14ONI[M+H]+: 472.0198, found: 472.0197 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =9.20 min, t (minor) =17.80 min.
Example 21
(75.0 Mg,76% yield,94% ee): melting point 218.8-220.7deg.C [ alpha ] D 21 = -162.3 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.83(s,1H),8.77(s,1H),8.73(d,J＝8.4Hz,1H),8.62(d,J＝ 8.0Hz,1H),8.48(d,J＝8.0Hz,1H),8.19(d,J＝7.2Hz,1H),8.10(t,J＝8.8Hz,2H),8.04-7.95(m,2H),7.85(d,J＝9.2Hz,1H),7.76(t,J＝7.6Hz,1H),7.72-7.64(m,2H),7.51(d,J＝8.4Hz,1H),7.35(t,J＝7.6 Hz,1H),6.76(t,J＝8.0Hz,1H),3.14(s,3H).13C NMR(100MHz,CDCl3)δ156.1,148.9,142.7,138.0, 135.6,132.7,132.6,131.3,131.0,130.8,130.5,129.4,129.1,129.0,128.9,128.8,128.0,127.7,127.2,127.1,127.1,126.6,126.4,126.4,126.0,125.9,125.7,125.0,124.7,123.7,123.1,97.9,23.5.IR( thin film ):νmax(cm-1) ＝2922,1577,1545,1525,1438,1414,1397,1379,1360,1284,1241,1216,1178,1164,1123,1079,1060,1040,1009,904,873,842,829,757,724,685,662,620,580;HRMS(ESI) calculated C 34H20NI[M+H]+: 570.0719. Found: 570.0712. Chiral column IC column, n-hexane/isopropyl alcohol=60/40, 1mL/min, detection wavelength=254 nm, t (major) =10.72 min, t (minor) = 21.51min.
Example 22
(63.1 Mg,93% yield,90% ee): melting point 121.6-123.5 ℃ [ α ] D 26 = +74.3 (c=0.2 chloroform ,90％ee).1H NMR(400MHz,CDCl3)δ8.75(d,J＝5.6Hz,1H),8.01(d,J＝8.8Hz,1H),7.95(d,J＝ 8.0Hz,1H),7.89(d,J＝8.4Hz,1H),7.81(d,J＝6.0Hz,1H),7.75-7.62(m,2H),7.47(t,J＝7.2Hz,1H),7.44-7.34(m,2H),7.29-7.23(m,1H),7.03(d,J＝8.8Hz,1H).13C NMR(100MHz,CDCl3)δ162.1,142.7, 141.3,136.6,135.5,133.8,132.9,130.6,130.1,128.2,127.8,127.6,127.3,127.2,127.0,126.6,126.4,120.9,97.3.IR( thin film ):νmax(cm-1)＝1712,1618,1578,1555,1497,1452,1404,1372,1337,1307,1258,1180,1138, 1105,1080,1043,1015,949,826,802,776,750,690,679,664,630,573,550,535,442;HRMS(ESI) calculated C 19H12NI[M+H]+: 382.0093, found: 382.0084. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.33 min, t (minor) =18.49 min.
Example 23
(63.1 Mg,91% yield,84% ee): melting point 138.7-140.8 ℃ [ α ] D 25 = +67.2 (c=0.2 chloroform ,84％ee).1H NMR(400MHz,CDCl3)δ8.73(d,J＝5.2Hz,1H),8.03(d,J＝8.4Hz,1H),7.94(d,J＝ 8.4Hz,1H),7.90(s,1H),7.79(d,J＝5.2Hz,1H),7.73-7.63(m,1H),7.50(t,J＝7.2Hz,1H),7.40(d,J＝4.0Hz,2H),7.25(t,J＝7.6Hz,1H),7.04(d,J＝8.4Hz,1H).13C NMR(100MHz,CDCl3)δ162.3,142.6, 139.6,136.9,136.6,135.9,133.7,132.2,130.6,127.8,127.7,127.2,127.1,126.9,126.3,124.5,120.8,97.3,19.2.IR( thin film ):νmax(cm-1)＝2919,1712,1647,1619,1580,1555,1503,1443,1411,1399,1378,1333,1320, 1303,1259,1237,1206,1157,1131,1068,1043,1031,1013,986,957,934,872,855,828,813,753,685,665,609,583,544,523,507,488,453,415;HRMS(ESI) calculated C 20H14NI[M+H]+: 396.0249, found: 396.0248 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.80 min, t (minor) = 24.89min.
Example 24
(80.6 Mg,98% yield,84% ee): melting point 174.1-176.0 ℃ [ α ] D 26 = +82.3 (c=0.2 chloroform ,84％ee).1H NMR(400MHz,CDCl3)δ8.82-8.66(m,1H),8.30(d,J＝8.4Hz,1H),7.93(d,J＝8.4 Hz,1H),7.84-7.75(m,1H),7.73-7.61(m,1H),7.52-7.37(m,3H),7.33(s,1H),7.29-7.21(m,1H),6.96(d,J＝8.8Hz,1H),4.05(s,3H).13C NMR(100MHz,CDCl3)δ162.2,155.6,142.5,136.5,134.0,133.7, 130.5,128.0,127.7,127.6,127.1,127.1,126.1,125.7,125.2,122.4,120.7,113.8,96.9,56.0.IR( thin film ):νmax(cm-1)＝2923,1713,1616,1575,1555,1505,1452,1436,1413,1367,1309,1260,1232,1161,1138,1102, 1041,1028,1014,986,933,877,829,806,769,751,693,682,663,631,612,564,532,513,462,424;HRMS (ESI) calculated C 20H14NOI[M+H]+: 412.0198, found: 412.0190 chiral column IC column, n-hexane/isopropanol=80/20, 1mL/min, detection wavelength=254 nm, t (major) =12.72 min, t (minor) = 37.20min.
Example 25
(82.2 Mg,91% yield,81% ee): yellow oily liquid [. Alpha. ] D 27 = +60.4 (c=0.2 chloroform ,81％ee).1H NMR(400MHz,CDCl3)δ8.74(d,J＝5.6Hz,1H),8.15(d,J＝8.8Hz,1H),7.96(d,J＝8.4Hz,1H),7.82(d,J＝5.6Hz,1H),7.78-7.64(m,2H),7.54(t,J＝8.0Hz,1H),7.44(t,J＝8.0Hz,1H),7.37(d,J＝8.4Hz, 1H),7.31(t,J＝8.4Hz,1H),7.02(d,J＝8.8Hz,1H).13C NMR(100MHz,CDCl3)δ161.4,158.0(d,J＝ 256.9Hz),142.6,137.6(d,J＝4.9Hz),136.6,134.4(d,J＝5.1Hz),130.7,128.3,127.9,127.7,127.3,126.8,126.8,126.4(d,J＝2.8Hz),123.4(d,J＝16.3Hz),121.1,121.0(d,J＝5.0Hz),119.4(d,J＝22.5Hz),95.0. IR( thin film ):νmax(cm-1)＝1711,1619,1587,1556,1503,1449,1413,1370,1332,1305,1258,1223,1155,1139, 1059,1042,1015,939,871,853,827,813,746,686,665,609,590,565,529,507,460,420;HRMS(ESI) calculated C 19H11NFI[M+H]+: 399.9998. Found: 399.9998. Chiral column IC column, n-hexane/isopropanol=80/20, 1mL/min, detection wavelength=254 nm, t (major) =6.34 min, t (minor) =10.51 min.
Example 26
(76.7 Mg,92% yield,75% ee): the yellow solid had a melting point of 140.8-142.9 ℃, [ α ] D 28 = +45.9 (c=0.2 chloroform ,75％ee).1H NMR(400MHz,CDCl3)δ8.74(d,J＝5.6Hz,1H),8.32(d,J＝8.4Hz,1H),8.15(s,1H), 7.95(d,J＝8.4Hz,1H),7.81(d,J＝6.0Hz,1H),7.69(t,J＝6.8Hz,1H),7.58(t,J＝8.0Hz,1H),7.42(t,J＝8.0Hz,1H),7.36(d,J＝8.0Hz,1H),7.31(t,J＝8.0Hz,1H),7.05(d,J＝8.4Hz,1H).13C NMR(100MHz, CDCl3)δ161.3,142.7,140.8,136.6,135.0,134.3,133.0,130.7,130.4,128.1,127.9,127.6,127.5,127.3, 127.0,126.8,124.9,121.0,95.6.IR( thin film ):νmax(cm-1)＝1618,1580,1556,1500,1409,1390,1369,1332, 1319,1287,1254,1199,1163,1140,1068,1044,1014,966,912,875,837,808,798,754,700,670,606,573,546,525,492,452,416;HRMS(ESI) calculated as C 19H11NClI[M+H]+: 415.9703, found: 415.9693. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =6.88 min, t (minor) =13.73 min.
Example 27
(86.7 Mg,94% yield,75% ee): melting point 165.9-167.7 ℃ [ α ] D 28 = +54.8 (c=0.2 chloroform ,75％ee).1H NMR(400MHz,CDCl3)δ8.74(d,J＝5.6Hz,1H),8.35(s,1H),8.29(d,J＝8.4Hz,1H), 7.96(d,J＝8.4Hz,1H),7.82(d,J＝5.6Hz,1H),7.70(t,J＝7.6Hz,1H),7.57(t,J＝8.0Hz,1H),7.43(t,J＝8.0Hz,1H),7.36(d,J＝8.4Hz,1H),7.30(t,J＝8.0Hz,1H),7.03(d,J＝8.8Hz,1H).13C NMR(100MHz, CDCl3)δ161.3,142.6,141.4,138.4,136.6,134.4,131.5,130.7,128.1,128.0,127.8,127.6,127.5,127.3, 127.0,126.7,124.0,121.1,96.2.IR( thin film ):νmax(cm-1)＝1649,1617,1580,1555,1497,1469,1388,1368, 1319,1285,1252,1194,1162,1138,1067,1043,1013,957,894,875,836,798,752,694,680,662,603,567,542,523,485,450,413;HRMS(ESI) calculated C 19H11NBrI[M+H]+: 459.9198. Found: 459.9201 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =7.22 min, t (minor) =15.75 min.
Example 28
(89.7 Mg,98% yield,78% ee): melting point 171.0-173.1 ℃ [ alpha ] D 27 = +51.6 (c=0.2 chloroform ,78％ee).1H NMR(400MHz,CDCl3)δ8.76(d,J＝5.6Hz,1H),7.99(s,1H),7.96(d,J＝8.0Hz,1H), 7.92(d,J＝8.4Hz,1H),7.81(d,J＝5.6Hz,1H),7.73-7.66(m,1H),7.58-7.49(m,5H),7.49-7.42(m,2H),7.42-7.36(m,1H),7.27-7.21(m,1H),7.10(d,J＝8.4Hz,1H).13C NMR(100MHz,CDCl3)δ162.2, 142.8,142.4,140.8,139.1,136.6,136.1,134.0,131.4,130.6,130.1,128.5,127.9,127.8,127.7,127.2,127.1,126.8,126.6,126.5,120.8,96.9.IR( thin film ):νmax(cm-1)＝1619,1579,1553,1492,1444,1410,1372,1332, 1315,1274,1239,1206,1159,1135,1113,1072,1043,1014,962,921,909,883,827,807,767,748,728,702,684,666,642,626,585,552,531,505,463,437,412;HRMS(ESI) calculated C 25H16NI[M+H]+: 458.0406. Found: 458.0408 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm t (major) =6.77 min, t (minor) =13.54 min.
Example 29
(73.6 Mg,90% yield,81% ee): melting point 174.7-176.5 ℃, [ α ] D 25 = +58.8 (c=0.2 chloroform ,81％ee).1H NMR(400MHz,CDCl3)δ8.73(d,J＝6.0Hz,1H),7.92(d,J＝8.4Hz,1H),7.85(s,1H), 7.77(d,J＝5.6Hz,1H),7.67(t,J＝7.2Hz,1H),7.49-7.36(m,2H),7.31-7.20(m,2H),6.77(d,J＝8.0Hz,1H),3.44(s,4H).13C NMR(100MHz,CDCl3)δ161.8,148.4,145.9,142.7,138.8,136.8,136.6,131.7,130.4, 129.3,129.1,127.7,127.6,127.2,127.1,121.1,120.6,120.2,99.4,30.5,29.9.IR( thin film ):νmax(cm-1)＝2916, 1621,1600,1575,1556,1496,1446,1420,1398,1362,1333,1313,1268,1233,1205,1159,1126,1108,1053,1015,984,957,905,891,871,856,833,811,784,750,687,671,646,584,516,494,461,415;HRMS(ESI) calculated C 21H14NI[M+H]+: 408.0249. Found: 408.0243. Chiral column IC column, n-hexane/isopropanol=60/40, 1mL/min, detection wavelength=254 nm, t (major) =7.42 min, t (minor) =19.27 min.
Example 30
(83.6 Mg,99% yield,77% ee): the yellow solid had a melting point of 88.1-90.2 ℃, [ α ] D 27 = +18.4 (c=0.2 chloroform ,77％ee).1H NMR(400MHz,CDCl3)δ8.78(d,J＝5.6Hz,1H),8.03(d,J＝8.8Hz,1H),7.98(d,J＝8.4 Hz,1H),7.88(d,J＝5.6Hz,1H),7.74-7.66(m,1H),7.54(d,J＝8.4Hz,1H),7.50(d,J＝8.4Hz,1H),7.48-7.40(m,2H),7.33-7.26(m,1H),6.85(t,J＝8.0Hz,1H),6.02(d,J＝8.0Hz,1H).13C NMR(100MHz, CDCl3)δ160.4,156.4,156.1,142.8,138.1,137.1,136.6,130.8,128.0,127.8,127.2,126.8,126.7,125.3, 122.9,122.8,121.9,121.3,113.7,111.6,90.6.IR( thin film ):νmax(cm-1)＝1620,1582,1556,1497,1465,1439, 1408,1383,1356,1320,1299,1273,1249,1218,1206,1191,1139,1108,1020,922,872,849,827,803,745,700,665,641,626,598,574,542,498,462,427;HRMS(ESI) calculated as C 21H12NOI[M+H]+: 422.0042, found: 422.0042. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =10.11 min, t (minor) =19.45 min.
Example 31
(75.5 Mg,98% yield,84% ee): yellow oily liquid [. Alpha. ] D 25 = +49.9 (c=0.2 chloroform ,84％ee).1H NMR(400MHz,CDCl3)δ8.48(d,J＝5.2Hz,1H),7.93(d,J＝8.8Hz,1H),7.84(d,J＝8.0Hz,1H),7.59 (d,J＝8.4Hz,1H),7.47(t,J＝7.6Hz,1H),7.34(t,J＝8.0Hz,1H),7.16(d,J＝8.4Hz,1H),7.12(d,J＝4.8Hz,1H),2.87(s,2H),2.49-2.28(m,1H),2.19-1.99(m,1H),1.85-1.76(m,2H),1.75-1.59(dq,J＝21.8, 6.2Hz,2H).13C NMR(100MHz,CDCl3)δ160.0,147.3,146.4,142.7,135.4,133.0,132.8,132.0,129.4, 128.2,127.2,126.4,125.8,124.0,96.8,29.4,25.9,22.8,22.2.IR( thin film ):νmax(cm-1)＝2930,2857,2832,1615, 1580,1559,1501,1451,1428,1375,1310,1272,1245,1214,1187,1164,1103,1086,1064,1030,981,944,904,863,844,824,807,787,745,674,658,620,588,568,544,508,446,425;HRMS(ESI) calculated C 19H16NI[M+H]+: 386.0406. Found: 386.0395. Chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =6.01 min, t (minor) =12.13 min.
Example 32
(66.1 Mg,89% yield,61% ee): yellow oily liquid [. Alpha. ] D 27 = +10.9 (c=0.2 chloroform ,61％ee).1H NMR(400MHz,CDCl3)δ8.70(d,J＝6.0Hz,1H),7.98(d,J＝8.8Hz,1H),7.87(d,J＝8.0Hz,1H),7.69- 7.62(m,2H),7.58(d,J＝6.0Hz,1H),7.48(t,J＝7.6Hz,1H),7.32(t,J＝8.4Hz,1H),7.18(d,J＝8.4Hz, 1H).13C NMR(100MHz,CDCl3)δ159.8,155.5,145.8,144.4,140.7,135.5,133.1,132.9,130.1,128.1,127.2, 126.5,126.1,124.7,106.8,105.6,96.5.IR( film ):νmax(cm-1)＝1601,1580,1530,1502,1459,1441,1420, 1331,1311,1266,1237,1215,1146,1126,1102,1042,1009,915,902,865,846,811,778,745,664,626,590,546,525,455;HRMS(ESI) calculated C 17H10NOI[M+H]+: 371.9885. Found: 371.9872. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =5.73 min, t (minor) =10.16 min.
Example 33: asymmetric synthesis of axial chiral halobiaryl 3
To a dry Schlenk flask was added compound 1 (61.0 mg,0.2 mmol), compound 2 (71.2 mg,0.4 mmol), C8 (7.8 mg,0.005 mmol), agNO 3 (6.8 mg,0.04 mmol) and Cu (OAc) 2 (0.4 mmol), evacuated, and acetonitrile (2 mL) was added under an argon atmosphere. Heating to 40 ℃ to react. After the completion of the reaction, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, the solvent was removed under reduced pressure from the organic phase by rotary evaporator, and the residue was chromatographed on silica gel (PE/EA/Et 3 n=20/1/0.01) to give the corresponding product.
Example 34
(58.5 Mg,76% yield,95% ee): yellow solid melting point 188.6-190.4 ℃, [ α ] D 25 = +60.5 (c=0.2 chloroform ,95％ee).1H NMR(400MHz,CDCl3)δ8.88(d,J＝5.2Hz,1H),7.96(d,J＝8.8Hz,1H),7.90(t,J＝8.8 Hz,2H),7.86-7.74(m,4H),7.54-7.39(m,3H),7.27-7.19(m,1H),7.14(d,J＝8.4Hz,1H),7.07(t,J＝ 8.0Hz,1H).13C NMR(100MHz,CDCl3)δ156.4,144.2,141.2,138.2,133.3,133.1,133.0,132.7,130.5, 130.0,129.2,129.2,128.3,127.7,127.6,127.2,126.6,125.8,125.6,125.5,122.0,120.7.IR( thin film ):νmax(cm-1)＝1610,1580,1554,1503,1452,1422,1395,1365,1299,1266,1237,1201,1167,1145,1109,1018,990, 967,921,867,844,813,784,744,719,680,631,590,542,514,499,485,470,431;HRMS(ESI) calculated C 23H14NBr[M+H]+: 384.0388, found: 384.0385. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.18 min, t (minor) =14.50 min.
Example 35
(76.3 Mg,92% yield,94% ee): the yellow solid had a melting point of 192.5-194.3C [ α ] D 24 = +79.7 (c=0.2 chloroform ,94％ee).1H NMR(400MHz,CDCl3)δ8.84(d,J＝5.2Hz,1H),8.03-7.93(m,2H),7.90(d,J＝8.0Hz, 1H),7.81(d,J＝5.2Hz,1H),7.76(d,J＝8.8Hz,1H),7.67(d,J＝8.8Hz,1H),7.63-7.52(m,2H),7.35(t,J＝8.4Hz,1H),7.17(t,J＝8.0Hz,1H).13C NMR(100MHz,CDCl3)δ158.0,146.6,144.2,138.4,138.2, 133.3,133.2,132.5,130.8,130.3,129.4,129.1,127.9,127.3,125.9,124.9,124.3,122.3,98.7.IR( thin film ):νmax(cm-1)＝1605,1585,1573,1548,1508,1449,1419,1375,1309,1260,1236,1191,1168,1146,1109,1065, 1038,989,970,929,900,853,837,800,775,749,719,682,640,571,523,487,432;HRMS(ESI) calculated as C 19H11NClI[M+H]+: 415.9703. Found: 415.9690 chiral column IC column, n-hexane/isopropanol=90/10, 1ml/min, detection wavelength=254 nm, t (major) =16.51 min, t (minor) =18.85 min.
Example 36
(76.4 Mg,97% yield,95% ee): the yellow solid had a melting point of 200.5-202.4 ℃, [ α ] D 26 = +152.4 (c=0.2 chloroform ,95％ee).1H NMR(400MHz,CDCl3)δ8.94-8.72(m,1H),7.93(d,J＝8.4Hz,1H),7.91-7.82(m, 2H),7.80-7.71(m,2H),7.67(d,J＝8.8Hz,1H),7.53(t,J＝7.6Hz,1H),7.35(d,J＝8.0Hz,1H),7.30(t,J＝7.6Hz,1H),7.12(t,J＝7.6Hz,1H),1.92(s,3H).13C NMR(100MHz,CDCl3)δ160.2,148.0,144.6,138.4, 137.9,137.8,133.5,132.7,131.1,130.2,129.7,129.5,128.1,127.4,126.2,125.4,124.6,122.0,98.6,21.3.IR( thin film ):νmax(cm-1)＝1605,1584,1553,1508,1440,1409,1372,1310,1236,1169,1094,1064,1040,989, 928,875,852,829,769,749,718,684,641,574,540,520,486;HRMS(ESI) calculated as C 20H14NI[M+H]+: 396.0249, found: 396.0239. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =7.85 min, t (minor) =14.03 min.
Example 37
(72.4 Mg,88% yield,91% ee): melting point 194.4-196.2 ℃ [ α ] D 26 = +16.5 (c=0.2 chloroform ,91％ee).1H NMR(400MHz,CDCl3)δ8.90-8.73(m,1H),7.91(d,J＝8.8Hz,1H),7.86(d,J＝8.0Hz, 1H),7.78(d,J＝8.4Hz,1H),7.76-7.68(m,2H),7.64(d,J＝8.0Hz,1H),7.52(t,J＝7.6Hz,1H),7.30(t,J＝8.0Hz,1H),7.20(t,J＝8.0Hz,1H),7.05(d,J＝8.0Hz,1H),3.53(s,3H).13C NMR(100MHz,CDCl3)δ 157.7,157.5,144.1,138.0,137.7,133.2,132.1,132.0,130.8,129.6,129.1,127.5,127.0,125.9,125.3,124.9,121.8,111.6,99.1,56.1.IR( thin film ):νmax(cm-1)＝2953,1607,1582,1560,1509,1460,1424,1377,1309,1286, 1254,1237,1184,1167,1142,1105,1029,990,967,929,875,853,822,774,739,718,682,640,589,570,530,496,460;HRMS(ESI) calculated C 20H14ONI[M+H]+: 412.0198. Found: 412.0186 chiral column IC column, n-hexane/isopropanol=90/10, 1ml/min, detection wavelength=254 nm, t (major) =26.33 min, t (minor) =32.14 min.
Example 38
(72.3 Mg,85% yield,97% ee): melting point 113.0-115.2 ℃ [ alpha ] D 24 = +139.1 (c=0.2 chloroform ,97％ee).1H NMR(400MHz,CDCl3)δ8.89–8.75(m,1H),8.02-7.92(m,2H),7.88(d,J＝7.6Hz, 1H),7.82-7.73(m,2H),7.70(d,J＝7.6Hz,1H),7.63(d,J＝8.8Hz,1H),7.54(t,J＝7.2Hz,1H),7.36-7.19(m,2H),4.15(d,J＝13.2Hz,1H),3.96(d,J＝13.6Hz,1H),3.02(s,3H).13C NMR(100MHz,CDCl3) δ158.6,146.1,144.2,138.7,138.5,138.1,133.2,132.5,130.0,129.3,129.2,127.8,127.7,127.2,125.8,125.5,124.6,121.9,98.6,72.4,58.4.IR( thin film ):νmax(cm-1)＝2992,2883,2855,1606,1582,1554,1508,1440,1409, 1366,1309,1292,1235,1199,1174,1127,1100,978,922,904,875,853,803,773,755,718,684,644,624,573,525,490;HRMS(ESI) calculated as C 21H16ONI[M+H]+: 426.0355. Found: 412.0343. Chiral column IC column, n-hexane/isopropyl alcohol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =6.43 min, t (minor) =8.13 min.
Example 39
(67.7 Mg,98% yield,85% ee): melting point 104.0-106.0 ℃ [ alpha ] D 25 = +98.5 (c=0.2 chloroform ,85％ee).1H NMR(400MHz,CDCl3)δ8.66(d,J＝5.6Hz,1H),7.91(d,J＝8.4Hz,1H),7.83(d,J＝8.0 Hz,1H),7.76-7.65(m,2H),7.50(d,J＝4.0Hz,2H),7.32(d,J＝7.6Hz,1H),7.08(t,J＝8.0Hz,1H),1.97 (s,3H).13C NMR(100MHz,CDCl3)δ162.8,143.1,142.5,138.6,136.7,136.5,130.5,130.1,127.7,127.2, 126.9,126.5,120.5,98.8,21.0.IR( thin film ):νmax(cm-1)＝2919,1620,1582,1555,1495,1440,1380,1351, 1317,1239,1215,1136,1109,1015,999,970,908,874,827,798,775,752,732,682,645,581,543,522,497,451;HRMS(ESI) calculated C 16H12NI[M+H]+: 346.0093, found: 346.0087. Chiral column IC column, n-hexane/isopropanol=90/10, 1ml/min, detection wavelength=254 nm, t (major) =14.50 min, t (minor) =16.69 min.
Example 40
(65.1 Mg,90% yield,88% ee): melting point 129.7-131.8 ℃ [ α ] D 25 = +19.5 (c=0.2 chloroform ,88％ee).1H NMR(400MHz,CDCl3)δ8.66(d,J＝6.4Hz,1H),7.88(d,J＝8.0Hz,1H),7.74-7.64(m, 2H),7.59(d,J＝8.0Hz,1H),7.56-7.44(m,2H),7.15(t,J＝8.0Hz,1H),7.02(d,J＝8.4Hz,1H),3.61(s,3H).13C NMR(100MHz,CDCl3)δ160.6,158.2,142.5,136.4,132.9,131.3,131.1,130.2,127.4,127.4,127.0, 126.8,120.6,111.0,99.6,56.1.IR( thin film ):νmax(cm-1)＝2923,1618,1581,1560,1498,1448,1425,1381, 1352,1320,1281,1255,1214,1182,1166,1143 1119,1023,971,875,820,77,754,740,683,645,597,569,550,525,487,463,418;HRMS(ESI) calculated C 16H12NOI[M+H]+: 362.0042. Found: 362.0031 chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (minor) =6.99 min, t (major) =10.92 min.
Example 41
(71.1 Mg,95% yield,80% ee): yellow oily liquid [. Alpha. ] D 27 = +72.3 (c=0.2 chloroform ,80％ee).1H NMR(400MHz,CDCl3)δ8.64(d,J＝5.6Hz,1H),7.92(t,J＝7.2Hz,1H),7.77-7.67(m,2H),7.63(d,J＝7.6Hz,1H),7.53-7.47(m,2H),7.22(t,J＝7.6Hz,1H),4.16(d,J＝13.2Hz,1H),3.94(d,J＝12.8Hz,1H), 3.07(s,3H).13C NMR(100MHz,CDCl3)δ161.6,142.4,141.9,139.5,138.1,136.4,130.5,130.3,127.7, 127.4,127.2,127.1,126.7,120.8,99.1,72.4,58.3.IR( thin film ):νmax(cm-1)＝2922,2889,2819,1621,1583, 1559,1497,1438,1382,1350,1319,1242,1194,1133,1114,1094,1016,972,873,827,799,777,749,711,684,651,626,580,465;HRMS(ESI) calculated C 17H14NOI[M+H]+: 376.0198. Found: 376.0182. Chiral column IC column, n-hexane/isopropanol=90/10, 1ml/min, detection wavelength=254 nm, t (major) =17.16 min, t (minor) =19.30 min.
Example 42
(63.9 Mg,89% yield,82% ee): yellow oily liquid [. Alpha. ] D 27 = +57.8 (c=0.2 chloroform ,82％ee).1H NMR(400MHz,CDCl3)δ8.64(d,J＝6.0Hz,1H),7.91(d,J＝8.4Hz,1H),7.83(d,J＝8.0Hz,1H),7.72 (d,J＝6.0Hz,1H),7.71-7.66(m,1H),7.50(d,J＝4.0Hz,2H),7.38(d,J＝7.6Hz,1H),7.14(t,J＝7.6Hz,1H),2.25(q,J＝7.6Hz,2H),0.96(t,J＝7.6Hz,3H).13C NMR(100MHz,CDCl3)δ162.7,144.7,142.6, 142.4,136.6,136.5,130.5,130.3,128.4,127.6,127.3,127.1,126.8,120.6,99.1,27.6,15.1.IR( film ):νmax(cm-1)＝2965,2931,2871,1620,1583,1556,1497,1436,1381,1354,1318,1243,1212,1175,1137,1110, 1085,1061,1016,972,873,826,810,782,748,682,664,645,581,464,451;HRMS(ESI) calculated C 17H14NI [M+H]+: 360.0249. Found: 360.0235. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =5.35 min, t (minor) =19.30 min.
Example 43
(72.7 Mg,90% yield,83% ee): yellow oily liquid [. Alpha. ] D 27 = +56.1 (c=0.2 chloroform ,83％ee).1H NMR(400MHz,CDCl3)δ8.59(d,J＝5.6Hz,1H),8.21-8.13(m,2H),7.89(d,J＝8.0Hz,1H),7.71(d,J＝ 5.6Hz,1H),7.70-7.64(m,1H),7.50-7.43(m,2H),7.28(t,J＝8.0Hz,1H),3.91-3.72(m,2H),0.64(t,J＝7.2Hz,3H).13C NMR(100MHz,CDCl3)δ165.4,162.9,144.1,143.0,141.9,136.0,132.4,130.6,130.1, 129.9,127.5,127.4,127.0,126.4,120.4,100.5,61.0,13.3.IR( film ):νmax(cm-1)＝2979,2934,2901,1713, 1622,1584,1561,1498,1443,1378,1366,1352,1321,1280,1255,1195,1146,1088,1015,973,871,826,800,753,701,681,641,465,438;HRMS(ESI) calculated C 18H14NO2I[M+H]+: 404.0147. Found: 404.0148. Chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =10.59 min, t (minor) =21.53 min.
Example 44
(67.4 Mg,93% yield,81% ee): yellow oily liquid [. Alpha. ] D 27 = +34.1 (c=0.2 chloroform ,81％ee).1H NMR(400MHz,CDCl3)δ8.60(dd,J＝8.4,5.6Hz,1H),7.94(d,J＝8.4Hz,1H),7.86(d,J＝8.4Hz,1H), 7.62(d,J＝8.8Hz,1H),7.49(t,J＝7.6Hz,1H),7.37(t,J＝8.0Hz,1H),7.18-7.07(m,2H),1.94(s,3H).13C NMR(100MHz,CDCl3)δ167.7(d,J＝259.8Hz),163.2(d,J＝5.1Hz),149.3(d,J＝8.1Hz),141.3(d, J＝3.5Hz),135.4,133.0,132.7,129.9,128.4,127.5,126.6,125.6,121.2(d,J＝13.2Hz),110.8(d,J＝17.9Hz),96.6,10.6(d,J＝4.0Hz).IR( thin film ):νmax(cm-1)＝2924,1601,1565,1502,1462,1425,1382,1368,1314, 1263,1248,1168,1146,1106,1075,1055,968,879,865,838,823,808,778,744,677,660,569,519,418; HRMS(ESI) calculated C 16H11NFI[M+H]+: 363.9998. Found: 363.9987. Chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =4.86 min, t (minor) =7.33 min.
Example 45
(59.0 Mg,86% yield,83% ee): yellow oily liquid [. Alpha. ] D 25 = +39.4 (c=0.2 chloroform ,83％ee).1H NMR(400MHz,CDCl3)δ8.64(d,J＝4.0Hz,1H),7.94(d,J＝8.8Hz,1H),7.85(d,J＝8.0Hz,1H),7.69 (d,J＝7.6Hz,1H),7.61(d,J＝8.8Hz,1H),7.48(t,J＝8.0Hz,1H),7.41-7.29(m,2H),7.13(d,J＝8.4Hz,1H),2.01(s,3H).13C NMR(100MHz,CDCl3)δ160.2,147.4,142.5,138.2,135.4,133.0,132.8,132.6,129.6, 128.3,127.3,126.5,125.8,123.3,96.8,18.7.IR( thin film ):νmax(cm-1)＝2919,1615,1577,1565,1502,1444, 1377,1313,1266,1236,1216,1183,1131,1111,1094,967,866,851,826,805,785,745,688,666,627,599,578,545,439;HRMS(ESI) calculated C 16H12NI[M+H]+: 346.0093. Found: 346.0083. Chiral column IC column, n-hexane/isopropanol=60/40, 1ml/min, detection wavelength=254 nm, t (major) =5.27 min, t (minor) =8.55 min.
Example 46
(70.5 Mg,98% yield,77% ee): melting point 129.3-131.2 ℃ for [ alpha ] D 25 = +79.6 (c=0.2 chloroform ,77％ee).1H NMR(400MHz,CDCl3)δ8.41(dd,J＝4.4,1.6Hz,1H),7.93(d,J＝8.4Hz,1H),7.82(d,J ＝8.4Hz,1H),7.58(d,J＝8.8Hz,1H),7.48-7.38(m,2H),7.37-7.30(m,2H),7.23(d,J＝7.6Hz,1H),3.72(s,3H).13C NMR(100MHz,CDCl3)δ153.9,150.9,141.5,140.5,135.4,133.3,133.0,129.6,128.2,127.0, 126.3,126.0,124.2,118.7,97.4,55.8.IR( thin film ):νmax(cm-1)＝2929,1613,1566,1500,1455,1423,1377, 1310,1276,1232,1187,1130,1114,1095,1065,1007,967,913,877,848,822,794,762,741,691,668,621,601,579,546,523,470,414;HRMS(ESI) calculated as C 16H12NOI[M+H]+: 362.0042. Found: 362.0027 chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =8.54 min, t (minor) =17.6 min.
Example 47
(79.8 Mg,99% yield,63% ee): the yellow solid had a melting point of 90.5-92.5 ℃, [ α ] D 27 = +32.6 (c=0.2 chloroform ,63％ee).1H NMR(400MHz,CDCl3)δ8.93(dd,J＝4.8,1.6Hz,1H),8.49(dd,J＝8.0,1.6Hz,1H),7.91 (d,J＝8.8Hz,1H),7.83(d,J＝8.4Hz,1H),7.60(d,J＝8.4Hz,1H),7.53(dd,J＝8.0,4.8Hz,1H),7.45(t,J＝8.0Hz,1H),7.32(t,J＝8.4Hz,1H),7.12(d,J＝8.4Hz,1H).13C NMR(100MHz,CDCl3)δ165.3,161.1, 152.6,143.4,139.0,135.1,133.0,132.7,129.3,128.1,127.8,127.0,126.3,125.8,123.1,95.7,61.2,13.3.IR( thin film ):νmax(cm-1)＝2980,2933,2902,1712,1615,1578,1563,1502,1436,1366,1297,1267,1242,1203, 1138,1102,1078,1055,1014,971,864,808,782,743,669,624,597,578,439;HRMS(ESI) calculated as C 18H14NO2I[M+H]+: 404.0147, found: 404.0147. Chiral column IC column, n-hexane/isopropanol=80/20, 1ml/min, detection wavelength=254 nm, t (major) =7.78 min, t (minor) =13.29 min.
Effect example 1: asymmetric synthesis of axichiral phosphorus ligand compound V
To a dry Schlenk flask was added compound I-1 (86.2 mg,0.2 mmol), pd (OAc) 2 (2.3 mg,0.01 mmol), 1, 3-bis (diphenylphosphino) propane (DPPP) (4.1 mg,0.01 mmol) and, under vacuum, dioxane (2 mL), DIPEA (103.4 mg,0.8 mmol) and compound V (37.2 mg,0.4 mmol) under an argon atmosphere. Heating to 100 ℃ to react. After the completion of the reaction, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator, and the residue was separated by column chromatography on silica gel (PE/EA/Et 3 n=20/1/0.01) to give the corresponding product.
(76.4 Mg,78% yield,94% ee): white solid .1H NMR(400MHz,CDCl3)δ8.68(d,J＝4.8Hz, 1H),7.97-7.87(m,3H),7.84-7.75(m,3H),7.50-7.35(m,4H),7.32-7.20(m,5H),7.19-7.09(m,3H),7.04(t,J＝7.6Hz,2H),6.95(t,J＝7.6Hz,1H),6.89(t,J＝7.6Hz,2H).
Effect example 2: application of axichiral phosphorus ligand compound V in asymmetric catalysis
To a dry Schlenk flask was added compound 6 (66.6 mg,0.2 mmol), pd (dba) 2 (11.5 mg,0.02 mmol), V-1 (11.7 mg,0.024 mmol) and t BuONa (38.4 mg,0.4 mmol), evacuated and toluene (4 mL) and PhNH 2 (37.3 mg,0.4 mmol) under an argon atmosphere. Heating to 50 ℃ to react. After the completion of the reaction, the reaction was quenched with water, extracted with dichloromethane, washed with saturated sodium chloride solution, dried over anhydrous Na 2SO4, filtered, the organic phase was freed from the solvent under reduced pressure by rotary evaporator, and the residue was separated by column chromatography on silica gel (PE/EA/Et 3 n=10/1/0.01) to give the corresponding product.
(49.2mg,71％yield,78％ee)。

Claims (12)

1. A process for the preparation of an axial chiral halobiaryl compound 3, characterized in that it comprises the following steps: in the presence of rhodium catalyst, silver salt and copper salt in an organic solvent under the atmosphere of protective gas, carrying out halogenation reaction on a compound shown in a formula I and a compound shown in a formula II to obtain a compound 3;
The compound 3 is a compound shown in a formula III and/or a compound shown in a formula III';
Wherein,
The solvent is one or more of hexafluoroisopropanol, halogenated hydrocarbon solvents, benzene solvents, nitrile solvents and amide solvents;
The halogenation reaction is free of additives or added with additives, when added, the additives are one or more of NaOTf, pivOCs, pivOH and 4-CF 3 PhCOOH;
The rhodium catalyst is a monovalent rhodium catalyst and/or a trivalent rhodium catalyst;
When the rhodium catalyst is a monovalent rhodium catalyst, the monovalent rhodium catalyst is Or an enantiomer thereof;
when the rhodium catalyst is a trivalent rhodium catalyst, the trivalent rhodium catalyst is
Wherein R 8 and R 8' are independently H, C 1-C8 alkyl, substituted or unsubstituted C 3-C8 cycloalkyl; r 9 and R 9' are independently H; r 10 and R 10' are independently H, C 1-C8 alkoxy;
the silver salt is one or more of AgSbF 6、AgF、AgNTf2、AgOTf、AgBF4、AgNO3 and i PrCOOAg;
the copper salt is Cu (OAc) 2;
Wherein X is halogen;
r 1 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8, aryl of C 6-C12, or aryl of C 6-C12 substituted with one or more R 1-1;
R 1-1 is halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
R 2 is hydrogen, halogen or alkyl of C 1-C8;
R 3 is halogen, hydroxymethyl, aldehyde, acetyl, cyano, C 1-C8 alkyl, C 1-C8 alkoxy, C 2-C8 oxaalkyl or
R 3-1 is hydrogen or alkyl of C 1-C8;
R 4 is aldehyde, cyano, carboxyl, trifluoromethyl, C 1-C8 alkyl, C 1-C8 alkoxy or
R 4-1 is hydrogen or alkyl of C 1-C8;
R 5 is hydrogen, halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
R 6 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8, aryl of C 6-C12, or aryl of C 6-C12 substituted with one or more R 6-1;
r 6-1 is halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
Or R 2 and R 3 together with the carbon atoms in between form: aryl of C 6-C14, aryl of C 6-C14 substituted with one or more R 23-1, 5-10 membered heteroaryl, or 5-10 membered heteroaryl substituted with one or more R 23-2; when multiple substituents are present, the same or different; the hetero atom is selected from N, O and S, and the number of the hetero atoms is 1-3 in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 23-2;
R 23-1 and R 23-2 are independently halogen, alkyl of C 1-C8 or alkoxy of C 1-C8;
or R 1、R2 and R 3 together with the carbon atoms in between form: aryl of C 10-C14 or aryl of C 6-C10 and cycloalkenyl of C 3-C7;
or R 4 and R 5 together with the carbon atom therebetween form a C 5-C8 cycloalkenyl, a C 6-C14 aryl, a C 6-C14 aryl substituted with one or more R 45-1, a 5-10 membered heteroaryl, or a 5-10 membered heteroaryl substituted with one or more R 45-2; when multiple substituents are present, the same or different; the hetero atom is selected from N, O and S, and the number of the hetero atoms is 1-3 in the 5-10 membered heteroaryl or the 5-10 membered heteroaryl in the 5-10 membered heteroaryl substituted by one or more R 45-2;
R 45-1 and R 45-2 are independently halogen, alkyl of C 1-C8 or alkoxy of C 1-C8.
2. The method of claim 1, wherein one or more of the following conditions are satisfied;
(1) When X is halogen, the halogen is Cl, br or I;
(2) When R 1 is halogen, the halogen is F, cl, br or I;
(3) When R 1 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(4) When R 1 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(5) When R 1 is aryl of C 6-C12, the aryl of C 6-C12 is phenyl, naphthyl or phenanthryl;
(6) When R 1 is aryl of C 6-C12 substituted by one or more R 1-1, the number of R 1-1 is 1-3;
(7) When R 1 is aryl of C 6-C12 substituted with one or more R 1-1, the aryl of C 6-C12 is phenyl or naphthyl;
(8) When R 1-1 is halogen, the halogen is F, cl, br or I;
(9) When R 1-1 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(10) When R 1-1 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(11) When R 2 is halogen, the halogen is F, cl, br or I;
(12) When R 2 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(13) When R 3 is halogen, the halogen is F, cl, br or I;
(14) When R 3 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(15) When R 3 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(16) When R 3 is C 2-C8 oxaalkyl, said C 2-C8 oxaalkyl is C 2-C4 oxaalkyl;
(17) When R 3-1 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(18) When R 4 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(19) When R 4 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(20) When R 4-1 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(21) When R 5 is halogen, the halogen is F, cl, br or I;
(22) When R 5 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(23) When R 5 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(24) When R 6 is halogen, the halogen is F, cl, br or I;
(25) When R 6 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(26) When R 6 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(27) When R 6 is aryl of C 6-C12, the aryl of C 6-C12 is phenyl, naphthyl or phenanthryl;
(28) When R 6 is aryl of C 6-C12 substituted by one or more R 6-1, the number of R 6-1 is 1-3;
(29) When R 6 is aryl of C 6-C12 substituted with one or more R 6-1, the aryl of C 6-C12 is phenyl, naphthyl or phenanthryl;
(30) When R 6-1 is halogen, the halogen is F, cl, br or I;
(31) When R 6-1 is C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(32) When R 6-1 is C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(33) When R 2 and R 3 together with the carbon atom between them form a C 6-C14 aryl group, said C 6-C14 aryl group is phenyl or naphthyl;
(34) When R 2 and R 3 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 23-1, the number of R 23-1 is 1-3;
(35) When R 2 and R 3 together with the carbon atom therebetween form an aryl group of C 6-C14 substituted by one or more R 23-1, said aryl group of C 6-C14 is phenyl, naphthyl or phenanthryl;
(36) When R 2 and R 3 together with the carbon atom therebetween form a 5-10 membered heteroaryl, said 5-10 membered heteroaryl is benzofuranyl;
(37) When R 23-1 and R 23-2 are independently halogen, said halogen is F, cl, br or I;
(38) When R 23-1 and R 23-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(39) When R 23-1 and R 23-2 are independently C 1-C8 alkoxy, said C 1-C8 alkoxy is C 1-C4 alkoxy;
(40) When R 1、R2 and R 3 together with the carbon atom therebetween form an aryl group of C 10-C14, said aryl group of C 10-C14 is an aryl group of C 10-C12;
(41) When R 1、R2 and R 3 together with the carbon atom therebetween form an aryl of C 6-C10 and a cycloalkenyl of C 3-C7, said aryl of C 6-10 and cycloalkenyl of C 3-7 is aryl of C 6-10 and cycloalkenyl of C 5-6;
(42) When R 4 and R 5 together with the carbon atom therebetween form a C 5-C8 cycloalkenyl group, said C 5-C8 cycloalkenyl group is a cyclopentenyl group or a cyclohexenyl group;
(43) When R 4 and R 5 together with the carbon atom therebetween form an aryl group of C 6-C14, said aryl group of C 6-C14 is phenyl, naphthyl or phenanthryl;
(44) When R 4 and R 5 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 45-1, the number of R 45-1 is 1-3;
(45) When R 4 and R 5 together with the carbon atom therebetween form an aryl group of C 6-C14 substituted by one or more R 45-1, said aryl group of C 6-C14 is phenyl, naphthyl or phenanthryl;
(46) When R 4 and R 5 together with the carbon atom therebetween form a 5-10 membered heteroaryl group, the 5-10 membered heteroaryl group is furyl, pyrrolyl, thienyl, pyranyl or pyridyl;
(47) When R 4 and R 5 together with the carbon atoms therebetween form a 5-to 10-membered heteroaryl group substituted with one or more R 45-2, the number of R 45-2 is 1-3;
(48) When R 4 and R 5 together with the carbon atom therebetween form a 5-10 membered heteroaryl group substituted with one or more R 45-2, the 5-10 membered heteroaryl group is furyl, pyrrolyl, thienyl, pyranyl or pyridyl;
(49) When R 45-1 and R 45-2 are independently halogen, said halogen is F, cl, br or I;
(50) When R 45-1 and R 45-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl is C 1-C4 alkyl;
(51) When R 45-1 and R 45-2 are independently an alkoxy group of C 1-C8, the alkoxy group of C 1-C8 is an alkoxy group of C 1-C4;
(52) The silver salt is one or more of AgSbF 6、AgF、AgNTf2、AgOTf、AgBF4 and AgNO 3;
(53) The protective gas is one or more of helium, neon, nitrogen and argon.
3. The method of manufacturing of claim 2, wherein one or more of the following conditions are satisfied:
(1) When R 1 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(2) When R 1 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(3) When R 1-1 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(4) When R 1-1 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(5) When R 2 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(6) When R 3 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(7) When R 3 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(8) When R 3 is C 2-C8 oxaalkyl, the oxaalkyl of C 2-C8 is Me-O-CH 2-CH2 -or Me-O-CH 2 -;
(9) When R 3-1 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(10) When R 4 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(11) When R 4 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(12) When R 4-1 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(13) When R 5 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(14) When R 5 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(15) When R 6 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(16) When R 6 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(17) When R 6-1 is C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(18) When R 6-1 is C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy or tert-butoxy;
(19) When R 2 and R 3 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 23-1, the aryl group of C 6-C14 is
(20) When R 2 and R 3 together with the carbon atom therebetween form a 5-10 membered heteroaryl group, the 5-10 membered heteroaryl group is
(21) When R 23-1 and R 23-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(22) When R 23-1 and R 23-2 are independently C 1-C8 alkoxy, said C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy, tert-butoxy;
(23) When R 1、R2 and R 3 together with the carbon atom therebetween form an aryl group of C 10-C14, said aryl group of C 10-C14 is
(24) When R 1、R2 and R 3 together with the carbon atom therebetween form a C 6-C10 aryl and C 3-C7 cycloalkenyl group, said C 6-10 aryl and C 3-7 cycloalkenyl group is
(25) When R 4 and R 5 together with the carbon atom therebetween form a C 5-C8 cycloalkenyl group, said C 5-C8 cycloalkenyl group is
(26) When R 4 and R 5 together with the carbon atom therebetween form an aryl group of C 6-C14, said aryl group of C 6-C14 is
(27) When R 4 and R 5 together with the carbon atoms therebetween form an aryl group of C 6-C14 substituted by one or more R 45-1, the aryl group of C 6-C14 is
(28) When R 4 and R 5 together with the carbon atom therebetween form a 5-10 membered heteroaryl group, the 5-10 membered heteroaryl group is furyl, thienyl or pyrrolyl;
(29) When R 4 and R 5 together with the carbon atom therebetween form a 5-10 membered heteroaryl group substituted with one or more R 45-2, the 5-10 membered heteroaryl group is furyl, thienyl or pyrrolyl;
(30) When R 45-1 and R 45-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl is methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, isobutyl or tert-butyl;
(31) When R 45-1 and R 45-2 are independently C 1-C8 alkoxy, the C 1-C8 alkoxy is methoxy, ethoxy, isopropoxy, tert-butoxy.
4. A method of preparation as claimed in claim 3, wherein one or more of the following conditions are met:
(1) When R 1 is C 1-C8 alkyl, the C 1-C8 alkyl is methyl;
(2) When R 23-1 and R 23-2 are independently C 1-C8 alkyl, said C 1-C8 alkyl is methyl;
(3) When R 4 and R 5 together with the carbon atom therebetween form a 5-to 10-membered heteroaryl group, the 5-to 10-membered heteroaryl group is
(4) When R 4 and R 5 together with the carbon atom therebetween form a 5-10 membered heteroaryl group substituted with one or more R 45-2, the 5-10 membered heteroaryl group is
(5) When R 45-1 and R 45-2 are independently alkyl of C 1-C8, the alkyl of C 1-C8 is methyl.
5. The method of manufacturing of claim 2, wherein one or more of the following conditions are satisfied:
(1) X is Br or I;
(2) R 1 is hydrogen, halogen, alkyl of C 1-C8, alkoxy of C 1-C8 or aryl of C 6-C12;
(3) R 2 is hydrogen or halogen;
(4) R 3 is halogen, C 1-C8 alkyl, C 1-C8 alkoxy, C 2-C8 oxaalkyl or
(5) R 3-1 is C 1-C8 alkyl;
(6) R 4 is C 1-C8 alkyl, C 1-C8 alkoxy or
(7) R 5 is hydrogen or halogen;
(8) R 6 is hydrogen or alkyl of C 1-C8;
(9) R 2 and R 3 together with the carbon atom in between form a C 6-C14 aryl or 5-10 membered heteroaryl;
(10) R 1、R2 and R 3 together with the carbon atom in between form an aryl group of C 10-C14 or an aryl group of C 6-C10 and cycloalkenyl group of C 3-C7;
(11) R 4 and R 5 together with the carbon atom in between form a C 5-C8 cycloalkenyl, a C 6-C14 aryl or a 5-to 10-membered heteroaryl;
(12) When the solvent is a halogenated hydrocarbon solvent, the halogenated hydrocarbon solvent is dichloromethane and/or dichloroethane;
(13) When the solvent is benzene solvent, the benzene solvent is toluene;
(14) When the solvent is a nitrile solvent, the nitrile solvent is acetonitrile;
(15) When the solvent is an amide solvent, the amide solvent is N, N-dimethylformamide;
(16) The protective gas is argon;
(17) The molar concentration of the compound shown in the formula I is 0.01-0.5mol/L;
(18) The molar ratio of the rhodium catalyst to the compound shown as the formula I is 0.01-0.2:1;
(19) The molar ratio of the silver salt to the compound shown in the formula I is 0.02-0.8:1;
(20) The temperature of the halogenation reaction is 0-100 ℃;
(21) The reaction time of the halogenation reaction is 0.5-24 hours;
(22) The mol ratio of the copper salt to the compound shown in the formula I is 1-5:1.
6. The method of claim 5, wherein one or more of the following conditions are satisfied:
(1) The molar concentration of the compound shown in the formula I is 0.05-0.2mol/L;
(2) The molar ratio of the rhodium catalyst to the compound shown as the formula I is 0.02-0.1:1;
(3) The molar ratio of the silver salt to the compound shown in the formula I is 0.04-0.4:1;
(4) The temperature of the halogenation reaction is 25-80 ℃;
(5) The reaction time of the halogenation reaction is 1-15 hours;
(6) The mol ratio of the copper salt to the compound shown in the formula I is 1-3:1.
7. The process of claim 6, wherein the halogenation reaction is carried out for a period of from 2 to 12 hours.
8. A method of preparation as claimed in claim 3, wherein one or more of the following conditions are met:
(1) X is Br or I;
(2) R 1 is H, halogen, methyl, methoxy or phenyl;
(3) R 2 is H or halogen;
(4) R 3 is halogen, methyl, ethyl, methoxy, CH 3OCH2 -or EtO 2 C-;
(5) R 4 is methyl, methoxy or
(6) R 5 is H or halogen;
(7) R 6 is H or methyl;
(8) R 2 and R 3 together with the carbon atom therebetween form a phenyl or benzofuranyl group;
(9) R 1、R2 and R 3 together with the carbon atom therebetween form a 1H-phenalenyl, benzocyclopentenyl or fluorenyl group;
(10) R 4 and R 5 together with the carbon atom in between form cyclohexenyl;
(11) R 4 and R 5 together with the carbon atoms in between form a phenyl, naphthyl or phenanthryl group;
(12) R 4 and R 5 together with the carbon atom in between form a furyl group;
(13) Fragments of compounds of formula I Is that
(14) Fragments of compounds of formula IIs that
(15) The rhodium catalyst is selected from any one of the following structures:
(16) The silver salt is AgNO 3;
(17) The solvent is acetonitrile and/or N, N-dimethylformamide;
(18) The halogenation reaction is also added with additives which are NaOTf and/or 4-CF 3 PhCOOH;
(19) When the chiral catalyst is When compound 3 is in S configuration; when the chiral catalyst isCompound 3 is in the R configuration.
9. The method of manufacturing of claim 8, wherein one or more of the following conditions are satisfied:
(1) R 2 and R 3 together with the carbon atoms in between form
(2) R 1、R2 and R 3 together with the carbon atoms in between form
(3) R 4 and R 5 together with the carbon atoms in between form
(4) R 4 and R 5 together with the carbon atoms therebetween are formed as
(5) R 4 and R 5 together with the carbon atoms therebetween are formed as
10. The method of manufacturing of claim 8, wherein one or more of the following conditions are satisfied:
(1) The compound shown in the formula I is selected from any one of the following structures:
(2) The compound 3 has any one of the following structures or an enantiomer thereof:
(3) Compound 3 is in S configuration when chiral catalyst C1, C2, C5, C7 or C8 is in S configuration, or in S configuration when chiral catalyst C9, C10, C15, C16, C18, C19, C24, C25, C27, C28 is in R configuration;
(4) Compound 3 is in the R configuration when chiral catalyst C1', C2', C5', C7', or C8' is in the R configuration, or in the R configuration when chiral catalyst C9', C10', C15', C16', C18', C19', C24', C25', C27', C28' is in the S configuration.
11. The method of claim 1, wherein one or more of the following conditions are satisfied:
(1) In the presence of rhodium catalyst, silver salt and copper salt in an organic solvent under the atmosphere of protective gas, the compound shown in the formula I and the compound shown in the formula II undergo halogenation reaction; the organic solvent is a nitrile solvent; the chiral rhodium catalyst is The silver salt is AgNO 3; the copper salt is Cu (OAc) 2; the molar concentration of the compound shown as the formula 1 in the organic solvent is 0.05-0.2mol/L; the molar ratio of the rhodium catalyst to the compound shown as the formula 1 is 0.02-0.1:1; the molar ratio of the silver salt to the compound shown in the formula 1 is 0.04-0.4:1; the mol ratio of the copper salt to the compound shown in the formula 1 is 1-3:1;
(2) After the halogenation reaction is finished, the method also comprises post-treatment operation; the post-treatment comprises the following steps: quenching, extracting, separating and purifying; the solvent for quenching is water; the solvent for extraction is dichloromethane; the operation and method of separation and purification are column chromatography separation, and the developing solvent system of the column chromatography separation is alkane solvent/ester solvent/Et 3 N.
12. The method of claim 11, wherein the column chromatography is performed with a solvent/solvent esters/Et 3 n=1/10/0.016.
CN202210764992.XA 2022-06-29 Axial chiral halogenated biaryl compound and preparation method thereof Active CN114957103B (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105669766A (en) * 2016-03-03 2016-06-15 中国科学院上海有机化学研究所 Spiro-framework-based cyclopentadiene compounds, rhodium complexes, and synthesis method and application thereof

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105669766A (en) * 2016-03-03 2016-06-15 中国科学院上海有机化学研究所 Spiro-framework-based cyclopentadiene compounds, rhodium complexes, and synthesis method and application thereof

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