Diastereoselective electrophilic substitution of α-amino-substituted benzylic organometallics

Reductive metallation of a diastereoisomeric bicyclic 2-phenyloxazolidine derived from 2-hydroxymethylpiperidine occurs with racemization at the benzylic carbon atom. Reaction of intermediate organometallics with alkyl halides affords substituted amino alcohols in a highly syn-selective fashion. Observed diastereoselectivities are rationalized in terms of rapidly equilibrating epimeric intermediate organometallics, one of which reacts preferentially under appropriate reaction conditions. Deuteration of the same intermediates usually leads to deuterated amino alcohols with low diasteroselectivities, unless lithium is employed as the reducing agent and the resulting mixture is allowed to equilibrate before deuteration.