Method for producing optically active 2-methyl-alkanols

1. A process for preparing optically active 2-methylalkan-1-ol of the general formula (III)

comprising the steps of:

(i) carbonyl-selectively reducing 2-methylalk-2-en-1-al of the general formula (I)

to 2-methylalk-2-en-1-ol of the general formula (II)

(ii) enantioselectively hydrogenating the 2-methylalk-2-en-1-ol of general formula (II) to the optically active 2-methylalkan-1-ol of the general formula (III);

(iii) increasing the optical yield of the optically active 2-methylalkan-1-ol (III) obtained in step (ii) by subjecting it to a lipase-catalyzed acylation reaction;

wherein R is C 1 to C 10 alkyl.

2. The process according to claim 1 , wherein R is methyl.

3. The process according to claim 1 , wherein step (i) is carried out using a main group element hydride.

4. The process according to claim 1 , wherein step (i) is carried out using a heterogeneous hydrogenation catalyst.

5. The process according to claim 1 , wherein step (ii) is carried out using a transition metal complex catalyst.

6. The process according to claim 5 , wherein the transition metal of said transition metal complex catalyst is Ru, Rh, Ir, Pd, or Pt.

7. The process according to claim 5 , wherein said transition metal complex catalyst comprises a phosphorus-containing chiral compound as a ligand.

8. The process according to claim 7 , wherein said ligand is a phosphorus-containing chiral compound according to formulae (IV), (V), and (VI)

wherein:

R1, R2, R3, and R4, identically or differently, are substituted or unsubstituted aryl, heteroaryl, alkyl, or cycloalkyl;

R5, R5′, R6, R6′, R7, R7′, R8, and R8′, identically or differently, are H, halogen, alkyl, aryl, alkoxy, amino, or thio;

X and X′, identically or differently, are S, O, NR9, wherein

R9 is H, alkyl, aryl, acyl, and SO 2 R10, wherein

R10 is aryl, alkyl, fluoroalkyl, and CF 3 ; and

wherein said phosphorus-containing chiral compound possess the ability to develop atropisomerism in relation to two aryl or hetaryl systems.

9. The process according to claim 7 , wherein said ligand is a phosphorus-containing chiral compound according to formulae (IV), (V), and (VI)

wherein:

R1, R2, R3, and R4, identically or differently, are substituted or unsubstituted aryl, heteroaryl, alkyl, or cycloalkyl;

R5, R5′, R8, and R8′ identically or differently, are H, halogen, alkyl, aryl, alkoxy, amino, or thio;

R6, R6′, R7, and R7′ define one or more rings, which optionally further contain 1 or 2 double bonds and/or heteroatoms;

X and X′, identically or differently, are S, O, NR9, wherein

R9 is H, alkyl, aryl, acyl, and SO 2 R10, wherein

R10 is aryl, alkyl, fluoroalkyl, and CF 3 ; and

wherein said phosphorus-containing chiral compound possess the ability to develop atropisomerism in relation to two aryl or hetaryl systems.

10. The process according to claim 7 , wherein said transition metal complex catalyst comprises a ligand selected from the group consisting of (R)-2,2′-bis-diphenylphosphanyl-[1,1]binaphthalenyl; (S)-2,2′-bis-diphenylphosphanyl-[1,1′]binaphthalenyl; (R)-6,6′-bis-diphenylphosphanyl-2,3,2′,3′-tetrahydro-[5,5′]bi[benzo[1,4]dioxinyl]; (S)-6,6′-bis-diphenylphosphanyl-2,3,2′,3′-tetrahydro-[5,5]bi[benzo[1,4]dioxinyl]; (R)-7,7′-bis-diphenylphosphanyl-4,4′-dimethyl-3,4,3′,4′-tetrahydro-2H,2′H-8,8′]bi[benzo[1,4]oxazinyl]; and (S)-7,7′-bis-diphenylphosphanyl-4,4′-dimethyl-3,4,3′,4′-tetrahydro-2H,2′H-[8,8′]bi[benzo[1,4]oxazinyl].

11. The process according to claim 1 , wherein step (iii) is carried out using Amano lipase PS-D1 (CAS No. 9001-62-1), PS-C1 or PS-C2 as a lipase.

12. The process according to claim 1 , wherein step (iii) is carried out using succinic anhydride as an acylating agent.

13. The process according to claim 1 , wherein step (iii) is carried out in the presence of a solvent selected from the group consisting of THF, MTBE, diethyl ether, toluene, 1,4-dioxane, and mixtures thereof.

14. The process according to claim 1 , further comprising a distillation step to purify the 2-methylalk-2-en-1-ol (II) obtained in step (i) and which is carried out after step (i) but before step (ii).