Transition-Metal-Free Total Synthesis and Revision of the Absolute Configuration of Pipermethystine

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 sp3 carbons. The completion of the total synthesis revealed that the natural levo-isomer possesses the R absolute configuration, not S.