Effect of sulfide structure on enantioselectivity in catalytic asymmetric epoxidation of aldehydes: Mechanistic insights and implications

Bridged bicyclic sulfide 1 was originally found to provide high levels of asymmetric induction in sulfur ylide-mediated epoxidations. This sulfide possesses chirality in the [2.2.1] thioether moiety and the [2.2.1] camphor-derived carbocyclic moiety. To determine whether the optimal sulfide had been used, a diastereomer of sulfide 1 in which the stereochemistry of the [2.2.1] carbocycle was reversed (sulfide 5) was prepared and studied as an epoxidation catalyst. This diastereomer gave considerably lower levels of asymmetric induction than the original sulfide 1. From computational and x-ray studies it was found that sulfide 5 gave rise to a more hindered ylide, which reacted more reversibly with aldehydes leading to lower enantioselectivity. Conditions that reduced reversibility were also tested and high enantioselectivities were returned for sulfide 5 (similar to sulfide 1). The implications for the synthesis of chiral sulfides for asymmetric epoxidations are discussed.