Enantioselective Synthesis of Dihydropyridines Containing Quaternary Stereocenters Through Dearomatization of Pyridinium Salts

Abstract

Enantioselective synthesis of nonaromatic heterocycles containing a fully substituted stereogenic center is a challenging synthetic problem. We describe a strategy toward this problem involving dearomatization of N-alkylpyridinium salts using boronic acid nucleophiles. This dearomatization reaction is catalyzed by a rhodium(I)/BINAP catalytic system and delivers dihydropyridines that contain a fully substituted stereogenic center alpha to the ring nitrogen atom in high yields and enantioselectivities. The reaction is compatible with a wide range of functional groups such as halide, ester, amide, olefin, and free alcohol. Derivatization of dehydropyridine products allows synthesis of the functionalized tetrahydropyridines and piperidines.