Stereoselective Addition of 2-Phenyloxazol-4-yl Trifluoromethanesulfonate to N-Sulfinyl Imines: Application to the Synthesis of the HCV Protease Inhibitor Boceprevir

The stereoselective addition of 2-phenyloxazol-4-yl trifluoromethanesulfonate to N-sulfinylimines is described. Vinyl anions derived from enol triflate 2 undergo 1,2-addition with a variety of aldimines to afford the corresponding secondary sulfonamides as single diastereomers. The absolute stereochemistry was confirmed by X-ray crystallography which provides support that the reaction proceeds through an open, nonchelate transition state. This methodology has been applied to the synthesis of the ketoamide fragment of the protease inhibitor boceprevir.