Photocyclization-fragmentation route to di- and triquinanes: Stereocontrolled asymmetric synthesis of (-)-isocomene
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-Buchi 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 (-1-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. The interesting structural features and the challenge posed by triquinane natural products has stimulated considerable interest in their synthesis. We recently reported a new, general approach to the di- and triquinane frameworks that is well suited for the synthesis of some of these natural products.' Our strategy takes advantage of two powerful reactions to build molecular complexity-a Diels-Alder reaction to construct a norbornane, and a Paterno-Biichi reaction to form a latent diquinane (Scheme 1). The resulting highly-strained structures (e.g., 2) are fragmented with complete selectivity under reductive conditions to reveal quinane skeletons. The fragmentation can follow two different paths, depending on the electronic properties of the substituent (R) on 2. With alkyl substituted systems, the fragmentation follows only path A and yields diquinane-enones. On the other hand, the alternate fragmentation path takes place when R is a radical stabilizing group (RSG), such as an ester or a phenyl? Scheme 1