Alkylation of phenylglycinol-derived oxazolopiperidone lactams. Enantioselective synthesis of beta-substituted piperidines

The stereochemical outcome of the alkylation of a variety of phenylglycinol-derived oxazolopiperidone lactams is studied. The influence of the configuration of the C-8a stereocenter and the effect of the substituents at the C-8 and C-8a positions on the stereoselectivity of the reaction are discussed. The synthetic utility of these alkylation reactions is illustrated with the synthesis of cis and trans 3,5-disubstituted, 2,5-disubstituted, and 2,3,5-trisubstituted enantiopure piperidines, and the indole alkaloids 20R- and 20S-dihydrocleavamine.