US 9,358,532 B2 · Catalyst for asymmetric hydrogenation of imine, synthesis method and application thereof

Abstract

A chiral hydrogenated H8-BINOL bisphosphine compound is provided, with the structure shown as the following formula (I), wherein both R1 and R2 are halogen, H or C1-C10 aliphatic group; R3 is H or C1-C10 aliphatic group; R4 is halogen, amino, nitro, H, C1-C10 aliphatic group or C1-C10 aromatic group; and X is phenyl, substituted phenyl, cyclohexyl, substituted cyclohexyl, C6-C30 aromatic group, or C6-C30 heterocyclic aromatic group containing one or more heteroatoms selected from N, S, O. The present invention further provides a catalyst for an asymmetric catalytic hydrogenation reaction which contains the compound, wherein the catalyst can produce more than 90% of enantiomers and efficiency with the turnover number of greater than 100,000 in the asymmetric hydrogenation reaction of imines.

Claims16

Dependent claims

A chiral hydrogenated H8-BINOL bisphosphine compound with the structure shown as the following formula (I):

wherein both R1 and R2 are halogen, H or C1-C10 aliphatic group;
R3 is H or C1-C10 aliphatic group;
R4 is halogen, amino, nitro, H, C1-C10 aliphatic group or C1-C10 aromatic group;
and X is

1 more element

A method for preparing a chiral hydrogenated H8-BINOL bisphosphine compound having the following formula (I):

wherein both R1 and R2 are halogen, H or C1-C10 aliphatic group;
R3 is H or C1-C10 aliphatic group;
R4 is halogen, amino, nitro, H, C1-C10 aliphatic group or C1-C10 aromatic group;
and X is
the method comprising the steps of:
(1) converting (R)-III to (R)-IV as follows in sub-steps (1a) through (1h)
(1a) based on molar ratio of phenylethylamine (R)-III:n-BuLi:ClSiMe3:n-BuLi:ClPX2=1:1-3:1-3:3-6:1-5, dissolving phenylethylamine (R)-(III) in ethyl ether;
(1b) adding n-BuLi and then ClSiMe3 after continuous stirring of the reaction mixture at 0° C.;
(1c) adding n-BuLi to the reaction mixture after 0.5-10 h of reaction of the reaction mixture after step (1b);
(1d) carrying out the reaction for 2-10 h to obtain a resulting reaction mixture;
(1e) adding the resulting reaction mixture to a solution of ClPX2 with cooling;
(1f) allowing the reaction mixture to stand overnight at 0-50° C.;
(1g) adding 2M HCl to quench the reaction;
and
(1h) performing column chromatography to obtain a phosphine-amine compound (R)-IV;
(2) converting (R)-V to (R)-VI as follows in sub-steps (2a) through (2g)
(2a) based on weight ratio of BINOL(V):
rhodium/platinum on carbon catalyst:ethanol=1:0.01-0.2:1-10, adding BINOL(V), rhodium/platinum on carbon catalyst, and ethanol to an autoclave;
(2b) flushing with hydrogen several times;
(2c) warming up to 10-100° C.;
(2d) increasing hydrogen pressure to 5-40 atm;
(2e) after hydrogen is no longer absorbed in the reaction, cooling;
(2f) filtering;
and
(2g) removing the solvent under vacuum, thereby obtaining hydrogenated H8-BINOL(VI);
(3) converting (R)-VI to (R)-VII as follows in sub-steps (3a) through (3e)
(3a) based on molar ratio of the hydrogenated H8-BINOL(VI) obtained in step (2):
PCl3:2-methylpyrrolidone=1:5-10:0.001-0.01, charging hydrogenated H8-BINOL(VI) and PCl3 into a reaction flask;
(3b) adding 2-methylpyrrolidone;
(3c) heating under reflux to react until hydrogenated H8-BINOL(VI) is fully dissolved;
(3d) removing the solvent under vacuum leaving a residue;
and
(3e) recrystallizing the residue with n-hexane to obtain the hydrogenated phosphine-containing chloro-H8-BINOL(VII);
and
(4) converting (R)-VII to (R,R)-I as follows in sub-steps (4a) through (4f)
(4a) based on molar ratio of compound (R)-IV obtained in step (1h):
compound (R)-VII obtained in step (3e):Et3N (triethylamine)=1:1-2:3-5, dissolving compound (R)-VII in toluene;
(4b) adding a solution of compound (R)-IV and NEt3 in toluene at 0-50° C.;
(4c) warming the reaction mixture to 0-95° C.;
(4d) reacting for 1-30 h with stirring;
(4e) filtering;
and
(4f) removing the solvent, thereby obtaining the chiral hydrogenated H8-BINOL bisphosphine compound (R,R)-I.

40 more elements

Dependencies are inferred from the claim text.

Facts

Application

14/001,756Filed 2 Mar 2011

Priority

CN 2011 1 004824028 Feb 2011

Published

US 2014/0018548 A116 Jan 2014

Granted

7 Jun 2016

Term ends

Not estimatedThe source records don’t support an estimate.

Classification18 codes

B01J 31/2466
And phosphine-P atoms as ring members in the condensed ring system or in a further ring: comprising aliphatic or saturated rings
B01J 31/186
Phosphites , their isomeric phosphonates and RO-substitution derivatives thereof: mono- or diamide derivatives thereof
C07C 213/02
Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same…: by…
C07C 231/02
Preparation of carboxylic acid amides: from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines

Catalyst for asymmetric hydrogenation of imine, synthesis method and application thereof

Life of this patent

Catalyst for asymmetric hydrogenation of imine, synthesis method and application thereof

Life of this patent

Abstract

Claims16