Synthesis of nuevamine and a cyano-chilenine analog via divergent C(sp 3 )-H bond functionalization of isoindolinone derivatives.

Divergent C(sp 3 )-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.