Efficient synthesis of an α-trifluoromethyl-α-tosyloxymethyl epoxide enabling stepwise double functionalisation to afford CF3-substituted tertiary alcohols

The efficient synthesis of an alpha-trifluoromethyl-alpha-tosyloxymethyl epoxide is reported. This highly versatile building block may be reacted sequentially with two different nucleophiles to furnish alpha-trifluoromethyl tertiary alcohols. Furthermore, the two enantiomers of this key intermediate have been separated using chiral HPLC and the stereochemistry shown to be conserved during subsequent chemical manipulations. Finally, an enzyme-driven desymmetrisation approach has been successfully employed to confer chirality on an intermediate in the sequence. (c) 2008 Elsevier Ltd. All rights reserved.