Transition-metal-free total synthesis and revision of the absolute configuration of pipermethystine

Abstract

Starting from 3-hydroxy piperidines, a novel transition-metal-free strategy to 5-hydroxy-5,6-dihydro-2(1H)pyridones is reported. This unprecedented approach, which provides a practical, economical, and ecofriendly alternative to either the classical ring-closing metathesis of N-homoallyl-unsaturated amides or the dehydrogenation of amides, occurs by means of a triple C-H functionalization of three unreactive piperidine sp(3) carbons. The completion of the total synthesis revealed that the natural levoisomer possesses the R absolute configuration, not S.