An Enantio- and Diastereoselective Chemoenzymatic Synthesis of α-Fluoro β-Hydroxy Carboxylic Esters

Abstract

The trans-o-hydroxybenzylidene pyruvate aldolase-catalysed reactions between fluoropyruvate and many (hetero)aromatic aldehydes yield aldol adducts without subsequent dehydration. Treatment of the reaction products with hydrogen peroxide yields the corresponding syn-configured α-fluoro β-hydroxy carboxylic acids which have >98 % ee. The overall chemoenzymatic approach, in which fluoropyruvate serves as a fluoroacetate equivalent, may be exploited in the synthesis of polar building blocks and fragments with potential value in drug discovery.

Keywords: aldolase; asymmetric catalysis; chemoenzymatic synthesis; organofluorine compounds.