Mechanism and Origin of Stereoselectivity in Lewis Acid Catalyzed [2+2] Cycloadditions of Ketenes with Aldehydes

Divergent rate-limiting steps for the formation of diastereomeric products! Evidence for this unexpected finding comes from experimental and theoretical studies of the title reaction. The predicted differing rate-determining steps (rds) in the formation of cis- and trans-β-lactones (see scheme; cy=cyclohexyl, TBS=tert-butyldimethylsilyl) are used to explain the stereoselectivity of these reactions and suggest that a broader range of mechanistic possibilities should sometimes be considered in reactions leading to diastereomeric products.