Method for synthesizing optically active carbonyl compounds

Patent metadata

Field	Value
Publication number	US-9975837-B2
Application number	US-201515536524-A
Country	US
Kind code	B2
Filing date	Dec 18, 2015
Priority date	Dec 19, 2014
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The present invention relates to a process for the preparation of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α,β-unsaturated carbonyl compound with hydrogen in the presence of at least one optically active transition metal catalyst that is soluble in the reaction mixture and which has rhodium as catalytically active transition metal and a chiral, bidentate bisphosphine ligand, wherein the reaction mixture during the hydrogenation of the prochiral α,β-unsaturated carbonyl compound additionally comprises at least one compound of the general formula (I):

in which
R 1 , R 2 : are identical or different and are C 6 - to C 10 -aryl which is unsubstituted or carries one or more, e.g. 1, 2, 3, 4 or 5, substituents which are selected from C 1 - to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C 6 - to C 10 -aryl, C 1 - to C 6 -alkoxy and amino; Z is a group CHR 3 R 4 or aryl which is unsubstituted or carries one or more, e.g. 1, 2, 3, 4 or 5, substituents which are selected from C 1 - to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C 6 - to C 10 -aryl, C 1 - to C 6 -alkoxy and amino, wherein R 3 and R 4 are as defined in the claims and the description.

First claim

The invention claimed is:

1. A process for the preparation of an optically active carbonyl compound by asymmetric hydrogenation of a prochiral α,β-unsaturated carbonyl compound with hydrogen in the presence of at least one optically active transition metal catalyst that is soluble in the reaction mixture and which has rhodium as catalytically active transition metal and a chiral, bidentate bisphosphine ligand, wherein the reaction mixture during the hydrogenation of the prochiral α,β-unsaturated carbonyl compound additionally comprises at least one compound of the general formula (I):

in which
R 1 , R 2 : are identical or different and are C 6 - to C 10 -aryl which is unsubstituted or carries one or more substituents which are selected from C 1 - to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C 6 - to C 10 -aryl, C 1 - to C 6 -alkoxy and amino;
Z is a group CHR 3 R 4 or aryl which is unsubstituted or carries one or more substituents which are selected from C 1 - to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C 6 - to C 10 -aryl, C 1 - to C 6 -alkoxy and amino, in which
R 3 is C 1 - to C 4 -alkyl, C 1 - to C 4 -alkoxy-C 1 - to C 4 -alkyl, C 3 - to C 6 -cycloalkyl or C 6 - to C 10 -aryl, where one or two nonadjacent CH 2 groups in C 3 - to C 6 -cycloalkyl can also be replaced by an oxygen atom;
R 4 is C 1 - to C 4 -alkyl which is unsubstituted or carries a group P(═O)R 4a R 4b , C 1 - to C 4 -alkoxy, C 1 - to C 4 -alkoxy-C 1 - to C 4 -alkyl, C 3 - to C 6 -cycloalkyl or C 6 - to C 10 -aryl, where one or two nonadjacent CH 2 groups in C 3 - to C 6 -cycloalkyl can also be replaced by an oxygen atom, and where C 3 - to C 6 -cycloalkyl and C 6 - to C 10 -aryl are unsubstituted or carry one or more substituents which are selected from C 1 - to C 4 -alkyl, C 1 - to C 4 -alkoxy and amino;
or
R 3 , R 4 : together with the carbon atom to which they are bonded, are C 4 - to C 8 -cycloalkyl, in which one or two nonadjacent CH 2 groups in C 3 - to C 6 -cycloalkyl can also be replaced by an oxygen atom and where C 3 - to C 6 -cycloalkyl is unsubstituted or carries one or more substituents which are selected from C 1 - to C 4 -alkyl, C 1 - to C 4 -alkoxy and A-P(═O)R 4a R 4b , where A is a chemical bond or a C 1 - to C 4 -alkylene;
and
R 4a , R 4b : are identical or different and are phenyl which is unsubstituted or carries one or more substituents which are selected from C 1 - to C 6 -alkyl, C 3 - to C 6 -cycloalkyl, C 6 - to C 10 -aryl, C 1 - to C 6 -alkoxy and amino.

2. The process according to claim 1 , wherein Z in formula (I) is a group CHR 3 R 4 .

3. The process according to claim 2 , wherein the variables R 1 , R 2 , Z in formula (I) have the following meanings:
R 1 , R 2 : are identical or different and are phenyl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy;
Z is a group CHR 3 R 4 , in which
R 3 is C 1 - to C 4 -alkyl;
R 4 is C 1 - to C 4 -alkyl which is unsubstituted or carries a group P(═O)R 4a R 4b ;
or
R 3 , R 4 : together with the carbon atom to which they are bonded, is C 3 - to C 8 -cycloalkyl in which one or two CH 2 groups can be replaced by one or two oxygen atoms and where C 3 - to C 6 -cycloalkyl is unsubstituted or carries a group A-P(═O)R 4a R 4b and/or has 1, 2, 3 or 4 methyl groups as substituents;
where A is a chemical bond, CH 2 or CH(CH 3 ); and
R 4a , R 4b : are identical or different and are C 6 - to C 10 -aryl which is unsubstituted or carries 1, 2 or 3 substituents which are selected from methyl and methoxy.

4. The process according to claim 2 , in which
R 1 , R 2 : are unsubstituted phenyl;
R 3 is methyl;
R 4 is a group CH(CH 3 )—P(═O)R 4a R 4b in which R 4a and R 4b are in each case unsubstituted phenyl.

5. The process according to claim 1 , wherein the compound of the formula (I) is used in an amount of from 0.001 mol to 1 mol per mole of rhodium.

6. The process according to claim 1 , wherein the prochiral α,β-unsaturated carbonyl compound is a prochiral, α,β-unsaturated ketone or a prochiral, α,β-unsaturated aldehyde.

7. The process according to claim 1 , wherein the prochiral α,β-unsaturated carbonyl compound is selected from compounds of the general formula (II)

in which
R 5 , R 6 are different from one another and is in each case an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more, nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more identical or different substituents which are selected from OR 8 , NR 9a R 9b , halogen, C 6 - to C 10 -aryl and C 3 - to C 9 -hetaryl;
R 7 is hydrogen or an unbranched, branched or cyclic hydrocarbon radical having 1 to 25 carbon atoms which is saturated or has one or more nonconjugated ethylenic double bonds, and which is unsubstituted or carries one or more identical or different substituents which are selected from OR 8 , NR 9a R 9b , halogen, C 6 - to C 10 -aryl and C 3 - to C 9 -hetaryl;
or
R 7 together with one of the radicals R 5 or R 6 , can also be a 3- to 25-membered alkylene group, in which 1, 2, 3 or 4 nonadjacent CH 2 groups can be replaced by O or N—R 9c , where the alkylene group is saturated or has one or more nonconjugated ethylenic double bonds, and where the alkylene group is unsubstituted or carries or one or more identical or different substituents which are selected from OR 8 , NR 9a R 9b , halogen, C 1 - to C 4 -alkyl, C 6 - to C 10 -aryl and C 3 - to C 9 -hetaryl, where two substituents also together can be a 2- to 10-membered alkylene group, where the 2- to 10-membered alkylene group is saturated or has one or more nonconjugated ethylenic double bonds, and where the 2- to 10-membered alkylene group is unsubstituted or carries one or more identical or different substituents which are selected from OR 8 , NR 9a R 9b , halogen, C 6 - to C 10 -aryl and C 3 - to C 9 -hetaryl;
where
R 8 is hydrogen, C 1 - to C 6 -alkyl, C 6 - to C 10 -aryl, C 7 - to C 12 -aralkyl or C 7 - to C 12 -alkylaryl;
R 9a , R 9b are in each case independently of one another hydrogen, C 1 - to C 6 -alkyl, C 6 - to C 10 -aryl, C 7 - to C 12 -aralkyl or C 7 - to C 12 -alkylaryl or
R 9a and R 9b together can also be an alkylene chain having 2 to 5 carbon atoms, which can be interrupted by N or O; and
R 9c is hydrogen, C 1 - to C 6 -alkyl, C 6 - to C 10 -aryl, C 7 - to C 12 -aralkyl or C 7 - to C 12 -alkylaryl.

8. The process according to claim 1 , wherein the prochiral α,β-unsaturated carbonyl compound is selected from compounds of the general formula (IIa) and (IIb)

in which
R 5 , R 6 is in each case an unbranched or branched hydrocarbon radical having 2 to 25 carbon atoms which is saturated or has 1, 2, 3, 4 or 5 nonconjugated ethylenic double bonds.

9. The process according to claim 8 for the preparation of optically active citronellal of the formula (IV)

in which * designates the asymmetry center;
by asymmetric hydrogenation of geranial of the formula (IIa-1) or of neral of the formula (IIb-1)

10. The process according

Assignees

• Basf Se

Inventors

• Schelwies Mathias
• Paciello Rocco
• Heydrich Gunnar
• Wegner Günter
• Tebben Gerd-Dieter
• Haubner Martin
• Keller Andreas
• Bey Oliver
• Renz Stephanie
• Seeber Georg

Classifications

• C07C29/56

  by isomerisation · CPC title

• C07C29/172 Primary

  with the obtention of a fully saturated alcohol · CPC title

• C07C45/62 Primary

  by hydrogenation of carbon-to-carbon double or triple bonds · CPC title

• C07B2200/07

  Optical isomers · CPC title

• C07C2601/14

  The ring being saturated · CPC title