Diastereoselective Synthesis of 2-Phenyl-3-(trifluoromethyl)piperazines as Building Blocks for Drug Discovery

The synthesis of enantiomerically pure cis- and trans-2-phenyl-3-(trifluoromethyl)piperazines is described. It involved, as the key step, a diastereoselective nucleophilic addition of the Ruppert–Prakash reagent (TMSCF3) to α-amino sulfinylimines bearing Ellman’s auxiliary. This methodology allows an entry into hitherto unknown trifluoromethylated and stereochemically defined piperazines, key scaffold components in medicinal chemistry.