Nucleophilic displacements of non-racemic α-trifluoromethyl benzylic triflates

Effective protocols for the introduction of chiral zeta-trifluoromethyl benzyl moieties by nucleophilic displacement of enantiomerically enriched alpha-trifluoromethyl benzylic triflates are presented. The effects of Substrate electronics, solvent polarity, temperature, and base are Studied by measuring the diastereomeric or enantiomeric excesses of the displacement products formed by coupling a variety of alpha-trifluoromethyl benzylic triflates with a range Of nucleophiles including amines, carboxylates, thiols, and malonates. Preliminary investigations to elucidate the mechanism(s) involved in the loss Df stereochemical integrity at the benzylic center in the nucleophilic displacement reactions are also reported. (C) 2008 Published by Elsevier Ltd.