Process of asymmetric hydrogenation of ketals and acetals

Patent metadata

Field	Value
Publication number	US-2016185683-A1
Application number	US-201314652562-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 the asymmetric hydrogenation of a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde by molecular hydrogen in the presence of at least one chiral iridium complex. This process yields chiral compounds in a very efficient way and is very advantageous in that the amount of iridium complex can be remarkably reduced.

First claim

1 . A process of the asymmetric hydrogenation of a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde by molecular hydrogen in the presence of at least one chiral iridium complex to yield a ketal or acetal having at least one stereogenic carbon centre.

2 . The process according to claim 1 wherein the ketal or acetal is obtained from the reaction of the corresponding unsaturated ketone or the corresponding unsaturated aldehyde and an alcohol, particularly a monol or a diol, preferably an alcohol which 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.

3 . The process according to claim 1 wherein the unsaturated ketone or unsaturated aldehyde is a ketone or an aldehyde having a carbon-carbon double bond in the α,β-position to the C═O group.

4 . The process according to claim 1 wherein the unsaturated ketone or unsaturated aldehyde is a ketone or an aldehyde having a carbon-carbon double bond in the γ,δ-position to the C═O group.

5 . The process according to claim 1 wherein the unsaturated ketone or unsaturated aldehyde has the formula (I) or (II)

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) and (II) represent either a single carbon-carbon bond or a double carbon-carbon bond;
and wherein represents a stereogenic centre.

6 . The process according to claim 1 wherein the chiral iridium complex is an iridium complex having ligands bound to the iridium central atom and that exactly one of the ligands is an organic ligand bearing a stereogenic centre, particularly a chelating ligand bearing a stereogenic centre.

7 . The process according to claim 5 wherein the chiral iridium complex is a chiral iridium complex of formula (III-0)

wherein
P-Q-N stands for a chelating organic ligand comprising a stereogenic centre or has planar or axial chirality and has a nitrogen and phosphorous atom as binding site to the iridium centre of the complex;
Y 1 , Y 2 , Y 3 and Y 4 are independently from each other are hydrogen atoms, C 1-12 -alkyl, C 5-10 -cycloalkyl, or aromatic group; or at least two of them form together at least a two-valent bridged group of at least 2 carbon atoms; and
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 − .

8 . The process according to claim 1 wherein the chiral iridium complex has the formula (III)

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).

9 . The process according to claim 1 wherein 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 0.001 to about 1 mol-%, most preferably from 0.001 to 0.1 mol-%, based on the amount of the acetal or ketal.

10 . The process according to claim 1 wherein the hydrogenation is performed in the presence of an additive which is selected from the group consisting of organic sulfonic acids, transition metal salts of organic sulfonic acids, metal alkoxides, aluminoxanes, alkyl aluminoxanes and B(R) (3-v) (OZ) v ;
wherein v stands for 0, 1, 2 or 3 and
R stands for F, a C 1-6 -alkyl, a halogenated C 1-6 -alkyl, an aryl or halogenated aryl group; and
Z stands a C 1-6 -alkyl, a halogenated C 1-6 -alkyl, an aryl or halogenated aryl group.

11 . The process according to claim 10 , wherein the additive is selected from the group consisting of triflic acid, alkyl aluminoxanes, particularly methyl aluminoxane, ethyl aluminoxane, tetra alkoxy titanates, B(R) (3-v) (OZ) v ; particularly tri-isopropylborate and triethylborane and BF 3 , preferably in the form of a BF 3 etherate.

12 . The process according to claim 1 wherein the hydrogenation is done further in the presence of a halogenated alcohol, particularly of 2,2,2-trifluoroethanol.

13 . A process of manufacturing aldehydes or ketones having at least one stereogenic carbon centre comprising the steps
α) forming a ketal from an unsaturated ketone or an acetal of an unsaturated aldehyde and an alc

Assignees

• Dsm Ip Assets Bv

Inventors

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

Classifications

• C07B53/00 Primary

  Asymmetric syntheses · CPC title

• C07D311/72

  3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols · CPC title

• B01J2231/34

  Other additions, e.g. Monsanto-type carbonylations, addition to 1,2-C=X or 1,2-C-X triplebonds, additions to 1,4-C=C-C=X or 1,4-C=-C-X triple bonds with X, e.g. O, S, NH/N · CPC title

• C07D317/12 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to ring carbon atoms · CPC title

• C07D319/06

  not condensed with other rings · CPC title