Many biologically interesting natural products contain linear polyol chains with complex substitution patterns. Construction of these compounds requires diastereoselective reactions which can create the desired polyol products from acyclic starting material. The Leighton group has been exploring methods for polyol synthesis which rely on stereoselective hydro- and silylformylation reactions in the hopes that flexible and rapid routes to polyols can be developed. They recently reported an innovative stereoselective tandem intramolecular silylformylation allylsilyation reaction which creates 1,3,5 triol products. However, the reaction only allows for substitution at the 2 position, and products are restricted to a syn, syn triol system. This proposal aims to expand the synthetic utility of the silylformylation allylsilyation reaction in the context of a total synthesis of the anti- cancer compound Dolabelide D. Building on recent preliminary results from the Leighton group, the proposed synthesis expands the possibilities for substitution at the 2,3,4, and 6 position of 1,3,5 triols and 1,5 diols and aims to bring diversity to the stereochemical relationship of the alcohols. This would greatly improve the potential for rapid synthesis of diverse polyol systems, such as those found in Dolabelide D and other biologically important natural products, using silylformylation allylsilyation.
