Photocyclization-fragmentation route to di- and triquinanes: Stereocontrolled asymmetric synthesis of (-)-isocomene

Abstract

We recently reported a general approach to the di- and triquinane frameworks. The strategy takes advantage of two powerful reactions to build the molecular complexity, a Diels-Alder reaction to construct a norbornane, and a Paterno-Büchi reaction to form a latent diquinane. The key step in the strategy is a reductive fragmentation reaction which liberates the quinane skeleton. This presentation will focus on the successful implementation of this strategy to the first controlled asymmetric synthesis of (-)-isocomene. The chirality of the natural product is derived from a highly scalemic norbornene ester that is readily available via the Helmchen Diels-Alder reaction. Subsequent elaboration provides a strained ketoalkene. Selective fragmentation of strategic bonds and further transformations afford the natural product in optically pure form, in good overall yield. Recent results aimed at altering the "normal" course of the reductive fragmentation will also be described.