Study of biocatalysis and fluorous phase labeling for the kinetic and dynamic kinetic resolution of racemates

Abstract

A highly fluorinated ester, 2,2,2-trifluoroethyl 2H,2H,3H,3H-perfluoro undecanoate, was synthesized and used in the lipase-catalysed kinetic resolution of secondary alcohols via fluorous-phase labeling. The fluorous-tagged products were recovered easily, with a high e.e. of 98-99 % towards the R- enantiomer, by partitioning between a fluorous solvent and an organic solvent. The reaction rate with the fluorous ester was somewhat slower than with isopropenyl acetate. However, the enantiopurities of the products were high and comparable to that with the latter. The effect of solvent and lipase employed on the transesterification rate and enantioselectivity was also investigated. Different zirconium-based catalysts were used as racemising agent for the dynamic kinetic resolution (DKR) of 1-phenylethanol via either the Meerwein-Ponndorf-Verley Reduction a?? Oppenauer Oxidation (MPVO) or acid-catalysed pathway. Out of which, aluminium-free Zr-beta catalyst, which showed the least poisoning by isopropenyl acetate, resulted in 64 % of 1-phenyl ethyl acetate with an e.e.of 88 % after 24 h at 80 oC. Preliminary study on the DKR of 1-phenylethanol in a biphasic system of perfluorooctane/water with the fluorous ester, resulted in a conversion of 75 % of (R)-1-phenylethanol with a high e.e. of >99 %.