Method for preparing chiral alkyl compounds by asymmetric hydrogenation of olefins catalyzed by iron complex

Patent metadata

Field	Value
Publication number	US-12221409-B2
Application number	US-202318210771-A
Country	US
Kind code	B2
Filing date	Jun 16, 2023
Priority date	Jan 22, 2021
Publication date	Feb 11, 2025
Grant date	Feb 11, 2025

Abstract

Provided in the present invention is a method for preparing chiral alkyl compounds by the asymmetric hydrogenation reaction of iron complex catalysts catalysing olefins: using the disubstituted olefin shown in formula I as a raw material, atmospheric hydrogen as a hydrogen source, FeX2-8-OIQ complex as a catalyst, and a silane compound and acetonitrile as cocatalysts, and reacting for 12-24 hours under the action of a reducing agent to prepare the chiral alkyl compound shown in formula II. The method of the present invention has mild reaction conditions, simple operation, and high atom economy. In addition, the reaction does not require the addition of any other toxic transition metal (such as ruthenium, rhodium, and palladium), and has great practical application value in the synthesis of drugs and materials. The conversion rate of the reaction is also good, generally reaching >99%, and the enantioselectivity is also high, generally 70-99%.

First claim

What is claimed is:

1. A method for preparing chiral alkyl compounds by asymmetric hydrogenation of olefins catalyzed by iron complex catalyst, wherein the method is as follows: reacting a disubstituted olefin shown in Formula I as a raw material, atmospheric hydrogen as hydrogen source, FeX2-8-OIQ complex as catalyst, hydrosilane and acetonitrile as co catalysts, for 12-24 hours under the activation of a reducing agent, to prepare a chiral alkyl compound shown in Formula II; wherein;

in Formula II, * represents a chiral carbon atom;
in Formula I or Formula II, R 1 is C 2 ˜C 8 alkyl, naphthyl, a group shown in Formula III, or a N and O containing heterocyclic aryl group of C 4 ˜C 10 ;
in R 1 , the H on C 2 ˜C 8 alkyl is not substituted or substituted by at least one substituent A, selected from the group consisting of and the substituent A is selected from the group consisting of phenyl, naphthyl, heterocyclic aryl or substituted phenyl; heterocyclic aryl is indolyl, pyridinyl, pyrrolyl, thiophenyl and furanyl; substituted phenyl is the phenyl group in which H on phenyl is replaced by at least one substituent B, and the substituent B is selected from the group consisting of C 1 ˜C 3 alkyl, C 1 ˜C 3 alkoxy, halogen and C 1 ˜C 3 alkylthio;
in R 1 , the N and O containing heterocyclic aryl group of C 4 ˜C 10 is selected from the group consisting of pyridinyl, pyrrolyl, indolyl, benzodioxazolyl, benzoxazolyl and furanyl;
in R 1 , the H on naphthyl and the N and O containing heterocyclic aryl group of C 4 ˜C 10 are not substituted or substituted by at least one substituent C, and the substituent C is C 1 ˜C 3 alkyl or C 1 ˜C 3 alkoxy;

in R 1 , among the groups shown in Formula III, R 4 , R 5 , R 6 , R 7 , R 8 are selected from the group consisting of H, halogen, C 1 ˜C 2 alkyl, C 1 ˜C 3 alkoxy, benzyloxy, C 1 ˜C 3 alkylthio, tert butyl dimethyl siloxy, trifluoromethyl, dimethylamino, pinacol borate, d-borneoxy, citronellol oxy, menthol oxy or geraniol oxy, and when R 4 , R 5 , R 6 , R 7 , R 8 are all H, Formula III is phenyl; and halogen is F or Cl;
in Formula I or Formula II, R 2 is C 1 ˜C 8 alkyl, C 2 ˜C 8 alkenyl, phenyl or benzyl; the H on C 1 ˜C 8 alkyl and C 2 ˜C 8 alkenyl are not substituted or substituted by at least one substituent D selected from the group consisting of phenyl, substituted phenyl, C 1 ˜C 3 amino or 1,3-dioxolacyl;
or in Formula I or Formula II, R 1 and R 2 are connected into a ring to form C 9 ˜C 12 benzocycloalkyl; H on C 9 ˜C 12 benzocycloalkyl is not substituted or substituted by at least one substituent E, and the substituent E is selected from the group consisting of C 1 ˜C 3 alkyl, C 1 ˜C 3 alkoxy or halogen;
R 1 and R 2 are different substituents; wherein the catalyst FeX2-OIQ complex is an optically pure compound shown in Formula IV or its enantiomer or racemate;

wherein in Formula IV, R 9 is C1-C12 alkyl which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by one to three substituents A, or aryl A which is unsubstituted or substituted by 1-4 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl;
R 10 is selected from the group consisting of H, C1-C12 alkyl which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl B which is unsubstituted or substituted by 1-3 substituents A; the aryl B is phenyl or naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl;
R 11 , R 12 , R 13 , R 14 and R 15 are independently selected from the group consisting of H, C1-C12 alkyl, C1-C4fluoroalkoxy, F, CI, nitro and C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl;
R 16 and R 17 are independently selected from the group consisting of H and C1-C12 alkyl A which is unsubstituted or substituted by one or two C1-C4 alkoxy, C5-C12 cycloalkyl which is unsubstituted or substituted by 1-3 substituents A, or aryl A which is unsubstituted or substituted by 1-3 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl;

the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl;
R 18 is selected from the group consisting of C1˜C12 alkyl group that is not substituted or substituted by 1-2 C1˜C4 alkoxy, C5-C12 cycloalkyl which is not substituted or substituted by 1-3 substituents A, or aryl A which is not substituted or substituted by 1-3 substituents B; the aryl A is selected from the group consisting of benzyl, phenyl and naphthyl; the substituent A is selected from the group consisting of C1-C4 alkyl and C1-C4 alkoxy; and the substituent B is selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, F and Cl;
in Formula IV,* represents a chiral carbon atom;
X is selected from the group consisting of F, Cl, Br, I, OAc and CF3SO3--;

and wherein the reducing agent is selected from the groups consisting of sodium triethylborohydride, sodium tri-sec-butyl-borohydride, lithium triethylborohydride, sodium tert-butoxide, potassium tert-butoxide, lithium tert-butoxide, sodium tert-pentoxide, sodium ethoxide, sodium methoxide and potassium methoxide.

2. The method according to claim 1 , wherein R 1 is C 2 ˜C 8 alkyl, naphthyl, 6-methoxynaphthalyl, pyridinyl, 2-methoxypyridyl, indolyl, N-methylindolyl, benzodioxazolyl and the group shown in Formula III;
in R 1 , when R 1 is C 2 ˜C 8 alkyl, H on C 2 ˜C 8 alkyl is replaced by a substituent A, R 1 is selected from the group consisting of expressed as R A —(CH 2 ) n —, wherein n is an integer of 2 to 8, R A is a substituent A on the carbon chain, and R A is phenyl, naphthyl or p-methoxyphenyl;
the group shown in Formula III is phenyl or substituted phenyl with 1-2 substituents, and the substituent on the substituted phenyl is selected from the group consisting of halogen, C 1 ˜C 2 alkyl, C 1 ˜C 3 alkoxy, benzyloxy, C 1 ˜C 3 alkylthio, tert-butyl dimethyl siloxy, trifluoromethyl, dimethylamino, pinacol borate, d-borneol, citronellol-oxyl, menthol-oxyl and geraniol-oxyl;
R 2 is selected from the group consisting of C 2 ˜C 6 alkyl, C 2 ˜C 6 alkenyl, phenyl or benzyl; H on the C 2 ˜C 6 alkyl is not substituted or substituted by substituent D, R 2 is C 2 ˜C 6 alkyl, and when H on the alkyl is substituted by substituent D, R 2 is expressed as R D —(CH 2 ) m —, m is an integer of 2 to 6, and the substituent D is phenyl, C 1 ˜C 3 amino, 4-methoxyphenyl and 1,3-dioxolacyl.

3. The method according to claim 1 , wherein the catalyst FeX 2 -8-OIQ complex is a compound shown in

Assignees

• Univ Zhejiang

Inventors

• Lu Zhan
• Lu Peng
• Ren Xiang

Classifications

• B01J2531/842

  Iron · CPC title

• B01J2531/0244

  Pincer-type complexes, i.e. consisting of a tridentate skeleton bound to a metal, e.g. by one to three metal-carbon sigma-bonds · CPC title

• B01J2231/645

  of C=C or C-C triple bonds · CPC title

• B01J31/182

  comprising aliphatic or saturated rings · CPC title

• B01J31/1835

  comprising aliphatic or saturated rings · CPC title