ALKYLATION OF 2-LITHIO-N-METHYLPIPERIDINES AND 2-LITHIO-N-METHYLPYRROLIDINES - SCOPE, LIMITATIONS, AND STEREOCHEMISTRY

The scope and limitations of the alkylation of racemic and nonracemic 2-lithiopiperidines and -pyrrolidines, obtained by transmetalation of the corresponding stannanes, is reported. These organolithiums react with a variety of electrophiles to afford 2-substituted pyrrolidines and piperidines in excellent yield. With primary alkyl halides the reaction proceeds with net inversion of configuration at the metal-bearing carbon in the piperidines; in the pyrrolidines there is a mixture of inversion and retention, with the former predominating. With most carbonyl electrophiles (carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, benzaldehyde, and dialkyl ketones), retention is observed in both cases. Electrophiles such as benzophenone, benzyl bromide, and tert-butyl bromoacetate afford racemic coupling products. A mechanistic interpretation is presented.