US 12,221,409 B2
Method for preparing chiral alkyl compounds by asymmetric hydrogenation of olefins catalyzed by iron complex
Zhan Lu, Zhejiang (CN); Peng Lu, Zhejiang (CN); and Xiang Ren, Zhejiang (CN)
Assigned to Zhejiang University, Hangzhou (CN)
Filed by Zhejiang University, Zhejiang (CN)
Filed on Jun. 16, 2023, as Appl. No. 18/210,771.
Application 18/210,771 is a continuation of application No. PCT/CN2021/130103, filed on Nov. 11, 2021.
Claims priority of application No. 202110092710.1 (CN), filed on Jan. 22, 2021.
Prior Publication US 2024/0174588 A1, May 30, 2024
Int. Cl. C07C 41/20 (2006.01); B01J 31/12 (2006.01); C07B 35/02 (2006.01); C07B 53/00 (2006.01); C07C 5/03 (2006.01); C07C 17/354 (2006.01); C07C 37/055 (2006.01); C07D 209/08 (2006.01); C07D 317/22 (2006.01); C07D 317/50 (2006.01); B01J 31/22 (2006.01); C07F 15/02 (2006.01)
CPC C07C 41/20 (2013.01) [B01J 31/12 (2013.01); C07B 35/02 (2013.01); C07B 53/00 (2013.01); C07C 5/03 (2013.01); C07C 17/354 (2013.01); C07C 37/055 (2013.01); C07D 209/08 (2013.01); C07D 317/22 (2013.01); C07D 317/50 (2013.01); B01J 31/2217 (2013.01); C07C 2531/22 (2013.01); C07C 2602/12 (2017.05); C07C 2602/42 (2017.05); C07F 15/025 (2013.01)] 8 Claims
 
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;

OG Complex Work Unit Chemistry
in Formula II, * represents a chiral carbon atom;
in Formula I or Formula II, R1 is C2˜C8 alkyl, naphthyl, a group shown in Formula III, or a N and O containing heterocyclic aryl group of C4˜C10;
in R1, the H on C2˜C8 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 C1˜C3 alkyl, C1˜C3 alkoxy, halogen and C1˜C3 alkylthio;
in R1, the N and O containing heterocyclic aryl group of C4˜C10 is selected from the group consisting of pyridinyl, pyrrolyl, indolyl, benzodioxazolyl, benzoxazolyl and furanyl;
in R1, the H on naphthyl and the N and O containing heterocyclic aryl group of C4˜C10 are not substituted or substituted by at least one substituent C, and the substituent C is C1˜C3 alkyl or C1˜C3 alkoxy;

OG Complex Work Unit Chemistry
in R1, among the groups shown in Formula III, R4, R5, R6, R7, R8 are selected from the group consisting of H, halogen, C1˜C2 alkyl, C1˜C3 alkoxy, benzyloxy, C1˜C3 alkylthio, tert butyl dimethyl siloxy, trifluoromethyl, dimethylamino, pinacol borate, d-borneoxy, citronellol oxy, menthol oxy or geraniol oxy, and when R4, R5, R6, R7, R8 are all H, Formula III is phenyl; and halogen is F or Cl;
in Formula I or Formula II, R2 is C1˜C8 alkyl, C2˜C8 alkenyl, phenyl or benzyl; the H on C1˜C8 alkyl and C2˜C8 alkenyl are not substituted or substituted by at least one substituent D selected from the group consisting of phenyl, substituted phenyl, C1˜C3 amino or 1,3-dioxolacyl;
or in Formula I or Formula II, R1 and R2 are connected into a ring to form C9˜C12 benzocycloalkyl; H on C9˜C12 benzocycloalkyl is not substituted or substituted by at least one substituent E, and the substituent E is selected from the group consisting of C1˜C3 alkyl, C1˜C3 alkoxy or halogen;
R1 and R2 are different substituents; wherein the catalyst FeX2-OIQ complex is an optically pure compound shown in Formula IV or its enantiomer or racemate;

OG Complex Work Unit Chemistry
wherein in Formula IV, R9 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;
R10 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;
R11, R12, R13, R14 and R15 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;
R16 and R17 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;
R18 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.