Bronsted acid catalyzed regioselective aza-Ferrier reaction: a novel synthetic method for α-(N-Boc-2-pyrrolidinyl) aldehydes

摘要

The 1,4-elimination reaction of (Z)-N-Boc-2-(4-inethoxy-2-alkenyloxy)pyrrolidines (1) is shown to proceed with high (1E,3E)-stereoselectivity to afford N-Boc-2-(1,3-dienyloxy)pyr-rolidines (2); the Bronsted acid catalyzed aza-Ferrier reaction of the N-Boc-2-(1,3-dtenyloxy)pyrrolidines (2) provides α-(N-Boc-2-pyrrolidinyl) aldehydes (3) in excellent yields with high α-regioselectivities.rnThe Ferrier reaction of O-alkenyl acetals is a unique and powerful synthetic transformation since it can easily convert an O-C bond into a new C-C bond; hence, it has found wide application in the synthesis of oxygen-containing heterocycles such as tetrahydropyranyl derivatives and C-glycosides. The reaction proceeds via Lewis acid catalyzed cleavage of an O-C bond of an O,O-alkenyl acetal to generate the oxocarbenium ion and an enolate. Their recombination then affords the corresponding P-alkoxy carbonyl compound, but the reaction via an N-acyliminium ion intermediate (aza-Ferrier reaction) generated from N,O-alkenyl acetals has been quite limited.