Highly enantioselective synthesis of pipecolic acid derivatives via an asymmetric aza-Diels–Alder reaction

Very high asymmetric induction is observed in the aza-Diels–Alder reaction between dienes and the imine (R)-PhMeCH–NCHCO2PhMen*(where PhMen*= 8-phenylmenthyl), which bears matched auxiliaries on nitrogen and on the ester; reactions in trifluoroethanol, in the presence of trifluoroacetic acid (1 equiv.), give substituted pipecolic acid derivatives in ca 50% isolated yield, with only a single regio- and diastereo-isomer of the cycloadduct detectable in all cases (d.e.>95%).