Highly enantioselective formal aza-Diels–Alder reactions with acylhydrazones and Danishefskyʹs diene promoted by a silicon Lewis acid

Silicon Lewis acid 3 is effective for the promotion of highly enantioselective cycloaddition reactions of acylhydrazones with Danishefskyʹs diene (formal aza-Diels–Alder reactions). The reactions are conducted at ambient temperature for 15 min, and produce the products in good yield and with high levels of enantioselectivity. A remarkable solvent-dependent reversal in the sense of absolute stereochemical induction has been observed. The method has been applied to an efficient and stereoselective synthesis of the neurokinin 1 receptor antagonist casopitant.