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 w ith a variety of electrophiles to afford 2-substituted pyrrolidines an d piperidines in excellent yield. With primary alkyl halides the react ion proceeds with net inversion of configuration at the metal-bearing carbon in the piperidines; in the pyrrolidines there is a mixture of i nversion and retention, with the former predominating. With most carbo nyl electrophiles (carbon dioxide, dimethyl carbonate, methyl chlorofo rmate, pivaloyl chloride, benzaldehyde, and dialkyl ketones), retentio n is observed in both cases. Electrophiles such as benzophenone, benzy l bromide, and tert-butyl bromoacetate afford racemic coupling product s. A mechanistic interpretation is presented.