Ketone homologation to produce α-methoxyketones: application to conduritol synthesis

The scope of Trost’s sulfone homologation procedure for the conversion of ketones into their α-methoxylated higher homologues has been dramatically expanded. The use of zirconium (or hafnium) tetrachloride in the hydroxy sulfone rearrangement step gives good yields with the adducts of aryl alkyl ketones, dialkyl ketones and cycloalkanones, and the rearrangement occurs with total regioselectivity. Mechanistic observations are presented which account for the formation of α-hydroxy aldehydes as by-products and which indicate an efficient method for their preparation. Application of the homologation methodology to the stereoselective synthesis of dihydroconduritols is described.