Deprotonative Coupling of Pyridines with Aldehydes Catalyzed by an HMDS-Amide Base Generated <i>in Situ</i>

Abstract

Herein, the deprotonative functionalization of pyridine derivatives with aldehydes under ambient conditions has been demonstrated using an amide base generated in situ from a catalytic amount of CsF and a stoichiometric amount of tris(trimethylsilyl)amine (N(TMS) 3). Pyridine substrates bearing two electron-withdrawing substituents (i.e., fluoro, chloro, bromo, and trifluoromethyl moieties) at the 3-and 5-positions efficiently react at the 4-position with various aldehydes including arylaldehydes, pivalaldehyde, and cyclohexanecarboxaldehyde.