Oxidative Carbocation Formation in Macrocycles: Synthesis of the Neopeltolide Macrocycle

Abstract

Macrocyclic oxocarbenium ions can be formed from macrolactones that contain benzylic or allylic ether groups through oxidative carbon-hydrogen-bond activation mediated by 2,3-dichloro-4,5-dicyanoquinone (DDQ). The applicability of this efficient reaction to complex-molecule synthesis was demonstrated by its use in a brief formal synthesis of neopeltolide (see retrosynthetic scheme) to form the tetrahydropyrone ring.