ChemInform Abstract: Diastereoselective Synthesis of α,α,α′‐Trisubstituted Pyrrolidines and Piperidines by Directed Sequential Lithiation/Alkylation.

Abstract

The stereocontrolled synthesis of α,α,α′-trisubstituted pyrrolidines and piperidines has been accomplished through α′-lithiation/trapping of the corresponding α,α-disubstituted Boc-protected azaheterocycle with various electrophiles. The relative configuration of the major diastereomer has the α′-substituent trans to the α-aryl group in the pyrrolidines but cis to the α-aryl group in the piperidines. The diastereoselectivity of the lithiation/alkylation of pyrrolidines is unaffected by TMEDA but decreases in the presence of (−)-sparteine in diethyl ether.