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

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.