An enantio- and diastereoselective chemoenzymatic synthesis of α-fluoro β-hydroxy carboxylic esters

The trans-o-hydroxybenzylidene pyruvate aldolase-catalysed reactions between fluoropyruvate and many (het)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.