Directed functionalization of 1,2-dihydropyridines: stereoselective synthesis of 2,6-disubstituted piperidines.

Guillaume Pelletier, Léa Constantineau-Forget, André B Charette

Chemical communications (Cambridge, England) 2014 Jul 4

filter terms:

A practical and highly stereoselective approach to access 2,6-disubstituted piperidines using an amidine auxiliary is reported. Following the diastereoselective addition of Grignard reagents at the 2-position of an activated pyridinium salt, the amidine group directs a regioselective metalation at the 6-position, enabling further functionalization. A subsequent electrophilic quench or a Negishi cross-coupling could be performed, resulting in 2,6-disubstituted dihydropyridines. These were reduced to the saturated piperidine rings with high diastereoselectivity.

Citation

Guillaume Pelletier, Léa Constantineau-Forget, André B Charette. Directed functionalization of 1,2-dihydropyridines: stereoselective synthesis of 2,6-disubstituted piperidines. Chemical communications (Cambridge, England). 2014 Jul 4;50(52):6883-5