Using mixtures of e/z isomers to obtain quantitatively specific products by combining asymmetric hydrogenation and isomerization

Patent metadata

Field	Value
Publication number	US-2016185702-A1
Application number	US-201314652362-A
Country	US
Kind code	A1
Filing date	Dec 18, 2013
Priority date	Dec 18, 2012
Publication date	Jun 30, 2016
Grant date	—

Abstract

The present invention relates to a process of manufacturing compound having stereogenic centres from a mixture of E/Z isomers of unsaturated compounds having prochiral double bonds. The hydrogenation product has a specific desired configuration at the stereogenic centres. The process involves an asymmetric hydrogenation and an isomerization step. The process is very advantageous in that it forms the desired chiral product from a mixture of stereoisomers of the starting product in an efficient way.

First claim

1 . A process of manufacturing compound of formula (I-A) or (I-B) or an acetal or a ketal thereof from a mixture of E/Z isomers of compound of formula (I) or (II) or an acetal or a ketal thereof

wherein Q stands for H or CH 3 and m and p stand independently from each other for a value of 0 to 3 with the proviso that the sum of m and p is 0 to 3, and where a wavy line represents a carbon-carbon bond which is linked to the adjacent carbon-carbon double bond so as to have said carbon-carbon double bond either in the Z or in the E-configuration and where the substructures in formula (I) and (II) represented by s1 and s2 can be in any sequence;
and wherein the double bond having dotted lines ( ) in formula (I) or (II) represent either a single carbon-carbon bond or a double carbon-carbon bond;

comprising the steps
either
a1) separating an isomer having E-configuration from the mixture of E/Z isomers of compound of formula (I) or (II) or the acetal or ketal thereof;
and
b1) submitting the isomers having the Z-configuration of compound of formula (I) or (II) or the acetal or ketal thereof to cis/trans isomerisation and adding the isomerization product to the mixture of isomers of compound of formula (I) or (II) or the acetal or ketal thereof;
and
c1) submitting the separated isomer having the E-configuration of compound of formula (I) or (II) or the acetal or ketal thereof to hydrogenation by molecular hydrogen in the presence of a chiral iridium complex of formula (III) having the S-configuration at the stereogenic centre indicated by *;

or
a2) separating an isomer having Z-configuration from the mixture of E/Z isomers of compound of formula (I) or (II) or the acetal or ketal thereof;
and
b2) submitting the isomers having the E-configuration of compound of formula (I) or (II) or the acetal or ketal thereof to cis/trans isomerisation and adding the isomerization product to the mixture of isomers of compound of formula (I) or (II) or the acetal or ketal thereof;
and
c2) submitting the separated isomer having the Z-configuration of compound of formula (I) or (II) or the acetal or ketal thereof to hydrogenation by molecular hydrogen in the presence of a chiral iridium complex of formula (III) having the R-configuration at the stereogenic centre indicated by *;

wherein
n is 1 or 2 or 3, preferred 1 or 2;
X 1 and X 2 are independently from each other hydrogen atoms, C 1-4 -alkyl, C 5-7 -cycloalkyl, adamantyl, phenyl (optionally substituted with one to three C 1-5 -alkyl, C 1-4 -alkoxy, C 1-4 -perfluoroalkyl groups and/or one to five halogen atoms)), benzyl, 1-naphthyl, 2-naphthyl, 2-furyl or ferrocenyl;
Z 1 and Z 2 are independently from each other hydrogen atoms, C 1-5 -alkyl or C 1-5 -alkoxy groups;
or Z 1 and Z 2 stand together for a bridging group forming a 5 to 6 membered ring;
Y ⊖ is an anion, particularly selected from the group consisting of halide, PF 6 − , SbF 6 − , tetra(3,5-bis(trifluoromethyl)phenyl)borate(BAr F − ), BF 4 − , perfluorinated sulfonates, preferably F 3 C—SO 3 − or F 9 C 4 —SO 3 − ; ClO 4 − , Al(OC 6 F 5 ) 4 − , Al(OC(CF 3 ) 3 ) 4 − , N(SO 2 CF 3 ) 2 − N(SO 2 C 4 F 9 ) 2 − and B(C 6 F 5 ) 4 − ;
R 1 represents either phenyl or o-tolyl or m-tolyl or p-tolyl or a group of formula (IVa) or (IVb) or (IVc)

wherein R 2 and R 3 represent either both H or a C 1 -C 4 -alkyl group or a halogenated C 1 -C 4 -alkyl group or represent a divalent group forming together a 6-membered cycloaliphatic or an aromatic ring which optionally is substituted by halogens atoms or by C 1 -C 4 -alkyl groups or by C 1 -C 4 -alkoxy groups
R 4 and R 5 represent either both H or a C 1 -C 4 -alkyl group or a halogenated C 1 -C 4 -alkyl group or a divalent group forming together a 6-membered cycloaliphatic or an aromatic ring which optionally is substituted by halogens atoms or by C 1 -C 4 -alkyl groups or by C 1 -C 4 -alkoxy groups;
R 6 and R 7 and R 8 represent each a C 1 -C 4 -alkyl group or a halogenated C 1 -C 4 -alkyl group;
R 9 and R 10 represent either both H or a C 1 -C 4 -alkyl group or a halogenated C 1 -C 4 -alkyl group or a divalent group forming together a 6-membered cycloaliphatic or an aromatic ring which optionally is substituted by halogens atoms or by C 1 -C 4 -alkyl groups or by C 1 -C 4 -alkoxy groups;

and wherein * represents a stereogenic centre of the complex of formula (III).

2 . The process according to claim 1 characterized in that the compound of formula (I) or (II) are selected from the group consisting of 3,7-dimethyloct-6-enal, 3,7-dimethylocta-2,6-dienal, 3,7-dimethyloct-2-enal, 6,10-dimethylundeca-3,5,9-trien-2-one, 6,10-dimethylundeca-5,9-dien-2-one, 6,10-dimethylundec-5-en-2-one, 6,10-dimethylundec-3-en-2-one, 6,10-dimethylundec-3,5-diene-2-one, 6,10,14-trimethylpentadeca-5,9,13-trien-2-one, 6,10,14-trimethylpentadeca-5,9-dien-2-one, 6,10,14-trimethylpentadec-5-en-2-one and (R)-6,10,14-trimethylpentadec-5-en-2-one as well as all their possible E/Z-isomers.

3 . The process according to claim 1 characterized in that the compound of formula (I) or (II) is of formula (II) and particularly is selected from the group consisting of 6,10-dimethylundeca-3,5,9-trien-2-one, 6,10-dimethylundeca-5,9-dien-2-one, 6,10-dimethylundec-5-en-2-one, 6,10-dimethylundec-3-en-2-one, 6,10-dimethylundec-3,5-diene-2-one, 6,10,14-trimethylpentadeca-5,9,13-trien-2-one, 6,10,14-trimethylpentadeca-5,9-dien-2-one, 6,10,14-trimethylpentadec-5-en-2-one and (R)-6,10,14-trimethylpentadec-5-en-2-one as well as all their possible E/Z-isomers.

4 . The process according to any one of the preceding claims characterized in that the acetal or ketal of the compound of formula (I) or (II) is obtained by the reaction of the compound of formula (I) or (II) with an alcohol, particularly a monol or a diol, preferably an alcohol selected from the group consisting of is halogenated C 1 -C 8 -alkyl alcohol or which is selected from the group consisting of ethane-1,2-diol, propane-1,2-diol, propane-1,3-diol, butane-1,4-diol, butane-1,3-diol, butane-1,2-diol, butane-2,3-diol, 2-methylpropane-1,2-diol, 2-methylpropane-1,3-diol, 2,2-dimethylpropane-1,3-diol, 1,2-dimethylpropane-1,3-diol, 3-methylpentane-2,4-diol and 2-(hydroxymethyl)cyclohexanol, benzene-1,2-diol and cyclohexane-1,2-diols.

5 . The process according to any one of the preceding claims characterized in that R 1 in formula (III) of the chiral iridium complex of formula is selected from the group consisting of

6 . The process according to any one of the preceding claims characterized in that the chiral iridium complex is present during the hydrogenation in an amount in the range from 0.0001 to 5 mol %, preferably from about 0.001 to about 2 mol %, more preferably from about 0.01 to about 1 mol-%, based on the amount of the compound of formula (I) or (II) or the acetal or ketal thereof.

7 . The process according to any one of the preceding claims characterized in that the separation of isomers in step a1) or a2) is done by distillation.

8 . The process according to any one of the preceding claims characterized in that the cis/trans isomerisation in step b1) or b2) is done in the presence of a cis/trans isomerizati

Assignees

• Dsm Ip Assets Bv

Inventors

• Bonrath Werner
• Netscher Thomas
• Medlock Jonathan Alan
• Stemmler René Tobias
• Verzijl Gerardus Karel Maria
• De Vries Andreas Hendrikus Maria

Classifications

• C07C41/60

  Preparation of compounds having [IMAGE cpc-sch-C07C-0959.gif] groups or[IMAGE cpc-sch-C07C-0960.gif] groups · CPC title

• C07C45/62 Primary

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

• C07B2200/07

  Optical isomers · CPC title

• C07C41/20

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

• C07C45/67 Primary

  by isomerisation; by change of size of the carbon skeleton · CPC title