Synthesis of nuevamine and a cyano-chilenine analog via divergent C(sp3)–H bond functionalization of isoindolinone derivatives

Abstract

Divergent C(sp³)–H bond functionalizations of isoindolinone derivatives were developed to synthesize nuevamine, a cyano-chilenine derivative, and two related analogs. A copper-catalyzed C–H cross-dehydrogenative coupling (via cation formation) allowed the formation of a new C–C bond leading to the direct assembly of the isoindolo[1,2-a]isoquinolinone tetracyclic system of the nuevamine. The syntheses of the cyano-chilenine derivatives were carried out by installing two nitrile groups under basic conditions (via anion formation). Then, the isoindolobenzazepinic system of the chilenine skeleton was constructed by a Houben–Hoesch cyclization process. The present methodology has the advantage of not requiring the use of pre-functionalized substrates.