Simple Diastereoselectivity of the BF₃·OEt₂-Catalyzed Vinylogous Mukaiyama Aldol Reaction of 2-(Trimethylsiloxy)furans with Aldehydes

A comprehensive scan of the transition state space for the reaction of 2-(trimethylsiloxy)furan and methacrolein (24 combinations) offered a satisfactory explanation of the high like diastereoselectivity obtained experimentally in the Mukaiyama vinylogous aldol reaction of these and related partners. It was determined that the syn-γ-hydroxyalkylbutenolides are formed preferentially following a g+ orientation of the two reactants with the aldehyde in the s-trans conformation. Diastereoselectivity is shown to be caused by a combination of subtle effects favoring the formation of the like product.