Stereospecific formation of optically active 5-alkyl-4-methyl-3-[(trialkylsilyl)oxy]-2-([(trialkylsilyl)oxy]-methyl)tetrahydrofurans via diastereoselective epoxidation and rearrangement of 5-[(trialkylsilyl)oxy]-2-alken-1-ols

A novel method for the synthesis of a series of silyl ethers of 3-(silyloxy)tetrahydrofuran-2-methanols bearing substituents at all four carbon atoms of the ring has been developed. The process involves first non-aldol aldol reaction of the epoxy silyl ether 8 to give the anti aldol product 9, stereoselective olefination and reduction to the (E)- and (Z)-allylic alcohols 10 and 11, diastereoselective epoxidation of these alcohols to give any of the four diastereomeric epoxy alcohols 12-15, silylation of the alcohols to give the epoxy silyl ethers 27-30, and final Lewis acid catalyzed rearrangement of the epoxy silyl ethers to give the desired products 31-33 and 36. In the first three instances, good yields of the desired 3-(silyloxy)-2-((silyloxy)methyl)tetrahydrofurans were obtained. However, rearrangement of the epoxy silyl ether 27 gave a mixture of products, the bis-silyl ether 36 as well as the products of a second non-aldol aldol process. This hydride migration to give the 3,5-bis((trialkylsilyl)oxy)-2,4-dimethylalkanal 35 or its internally protected 1-(silyloxy)pyran 38 can be made to occur in good yield.