Process of asymmetric hydrogenation of ketals and acetals

Patent metadata

Field	Value
Publication number	US-9561989-B2
Application number	US-201314652562-A
Country	US
Kind code	B2
Filing date	Dec 18, 2013
Priority date	Dec 18, 2012
Publication date	Feb 7, 2017
Grant date	Feb 7, 2017

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

The invention claimed is:

1. A process for the asymmetric hydrogenation of a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde which comprises subjecting a ketal of an unsaturated ketone or an acetal of an unsaturated aldehyde to hydrogenation conditions with 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, 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.

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

3. The process according to claim 1 , wherein the unsaturated ketone or unsaturated aldehyde is an unsaturated ketone or unsaturated aldehyde according to formula (I) or formula (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
wherein 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 formula (II) represented by S1 and s2 can be in any sequence; and
wherein the double bond having dotted lines ( ) in formula (I) and formula (II) represent either a single carbon-carbon bond or a double carbon-carbon bond; and
wherein represents a stereogenic centre.

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

5. The process according to claim 3 , 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 Y 1 , Y 2 , Y 3 and Y 4 form together at least a two-valent bridged group of at least 2 carbon atoms; and
Y ⊖ is an anion selected from the group consisting of halide, PF 6 − , SbF 6 − , tetra(3,5-bis(trifluoromethyl)phenyl)borate (BAr F − ), BF 4 − , perfluorinated sulfonate, 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 − .

6. 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 selected from the group consisting of halide, PF 6 − , SbF 6 − , tetra(3,5-bis(trifluoromethyl)phenyl)borate(BAr F − ), BF 4 − , perfluorinated sulfonate, 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), formula (IVb) or formula (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;
each of R 6 , R 7 and R 8 represents C 1 -C 4 -alkyl group or a halogenated C 1 -C 4 -alkyl group;
R 9 and R 19 represent either both H, 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).

7. The process according to claim 1 , wherein the chiral iridium complex is present during the hydrogenation in an amount from 0.0001 to 5 mol-%, based on the amount of the acetal or ketal.

8. The process according to claim 1 , wherein the process comprises performing hydrogenation in the presence of an additive 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;
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.

9. The process according to claim 8 , wherein the additive is selected from the group consisting of triflic acid, alkyl aluminoxanes, tetra alkoxy titanates, tri-isopropylborate, triethylborane and BF 3 .

10. The process according to claim 1 , wherein the process comprises conducting hydrogenation in the presence of a halogenated alcohol.

11. The process according to claim 2 , wherein the alcohol is a monol or a diol.

12. The process according to claim 2 , wherein the alcohol is a halogenated C 1 -C 8 -alkyl alcohol.

13. The process according to claim 2 , wherein the alcohol 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-diol.

14. The process according to claim 4 , wherein organic ligand bearing a stereogenic centre is a chelating ligand bearing a stereogenic centre.

15. The process according to claim 5 , wherein Y ⊖ is F 3 C—SO 3 − or F 9 C 4 —SO 3 − .

16. The process according to claim 6 , wherein Y ⊖ is F 3 C—SO 3 − or F 9 C 4 —SO 3 − .

17. The process according to claim 7 , wherein the chiral iridium complex is present during the hydrogenati

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

• C07B2200/09

  Geometrical isomers · 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

• C07C41/56

  by condensation of aldehydes, paraformaldehyde, or ketones · CPC title

• C07B35/02 Primary

  Reduction · CPC title