Enantioselective Synthesis of 3,3-Disubstituted Piperidine Derivatives by Enolate Dialkylation of Phenylglycinol-Derived Oxazolopiperidone Lactams

The stereochemical outcome of the enolate dialkylation of simple phenylglycinol-derived oxazolopiperidone
lactams is studied. High stereoselectivities in the generation of the quaternary stereocenter are obtained
by the appropriate choice of both the configuration of the starting lactam and the order of introduction
of the substituents. The usefulness of the methodology is illustrated by the conversion of some of the
dialkylated lactams into known synthetic precursors of alkaloids and by the total synthesis of
(−)-quebrachamine.