Directed functionalization of 1,2-dihydropyridines: stereoselective synthesis of 2,6-disubstituted piperidines.
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.
FRQNT 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.
Guillaume
G
Pelletier
Léa
L
Constantineau-Forget
André B
AB
Charette
D000578:Amidines / Q000737:chemistry*; D004095:Dihydropyridines / Q000737:chemistry*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000578:Amidines; D004095:Dihydropyridines; D010880:Piperidines; C032727:piperidine