Catalytic Regioselective γ-Methylenation of α,β-Unsaturated Aldehydes Using Formaldehyde via Vinylogous Aldol Condensation.

The first vinylogous aldol condensation of α,β-unsaturated aldehydes using aqueous formaldehyde is developed under mild reaction conditions to form the γ-methylenated products with excellent regioselectivity. Using this methodology, a short synthesis of α-triticene, an antifungal compound, is achieved in two steps. The practicality of this methodology is demonstrated by the gram-scale synthesis. Formation of the unusual double γ-functionalized products from crotonaldehyde and a direct asymmetric vinylogous aldol product from phenylglyoxal is also described.