Racemization of secondary alcohols catalyzed by ruthenium: application to chemoenzymatic dynamic resolution

In this paper, we have shown that the [RuCl2(p-cymene)]2 complex associated with simple hemisalen ligands is able to racemize (S)-1-phenylethanol. The influence on the racemization process of the ligand’s structure as well as the nature of a co-catalyst have been evaluated and optimized. This [RuCl2(p-cymene)]2/Ligand/TEMPO racemization system was then associated with the Candida Antarctica B lipase in order to carry out dynamic kinetic resolution experiments on rac-phenylethanol. This led us to identify the best conditions for effective DKR, which was then applied to various secondary benzylic and aliphatic alcohols. It was thus possible to obtain (R)-1-cyclohexylethyl acetate from rac-1-cyclohexylethanol in quantitative conversion and with high enantioselectivity (98%).

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(R)-(+)-1-Phenylethyl acetateC10H12O2Ee >99%. By GC on CHIRALSIL-DEX CB column[α]D20=+136 (c 0.77, MeOH)Source of chirality: asymmetric catalysisAbsolute configuration: (R)

(R)-(+)-1-CyclohexylethylacetateC10H18O2Ee = 98%. By GC on CHIRALSIL-DEX CB column[α]D20=+9.3 (c 1.6, CHCl3)Source of chirality: asymmetric catalysisAbsolute configuration: (R)