Synthesis of γ-butyrolactams by photoinduced PhSe group transfer radical cyclization and formal synthesis of (±)-isocynometrine with diphenyldiselenide as promoter

Abstract

(Chemical Equation Presented) We have developed a strategy for constructing nitrogen heterocycles by photoinduced PhSe group transfer radical cyclization. trans-α,β-Disubstituted γ-butyrolactams (2-pyrrolidinones) were prepared in good yields (38-73%) with high regioselectivity and stereoselectivity from N-alkenyl α-PhSe β-keto amides. Reaction outcomes were modulated by the steric effect of the substituents on the nitrogen atom of the cyclization precursors and the stereoelectronic effect of the substrates. Diphenyldiselenide, as an additive, was found to promote ring closure. The advantage of this strategy in natural product synthesis is demonstrated by a formal synthesis of (±)-isocynometrine. © 2009 American Chemical Society.