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Directed functionalization of 1,2-dihydropyridines: stereoselective synthesis of 2,6-disubstituted piperidines
Guillaume Pelletier1, Léa Constantineau-Forget, André B Charette
1FRQNT Centre in Green Chemistry and Catalysis, Faculty of Arts and Sciences, Department of Chemistry, Université de Montréal, PO Box 6128, Station Downtown, Montréal, Québec, Canada H3C 3J7. andre.charette@umontreal.ca.
Abstract:
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.
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