Direct Catalytic Asymmetric Synthesis of Disubstituted 4-Oxocyclohexanecarbaldehydes from Acetone and Cinnamaldehyde Derivatives.

A first catalytic asymmetric reaction of acetone with cinnamaldehyde for the synthesis of disubstituted 4-oxocyclohexanecarbaldehyde is developed. A variety of substituted cinnamaldehydes are successfully tested under the optimized reaction conditions. Both the enantiomers of the same diastereomeric products are achieved in good yield and diastereoselectivity with an excellent enantioselectivity by changing the enantiomer of one of the two chiral catalysts. The practicality of this methodology is demonstrated by the gram-scale synthesis.

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

The first vinylogous aldol condensation of α,ß-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.