Direct catalytic asymmetric synthesis of disubstituted 4-oxocyclohexanecarbaldehydes from acetone and cinnamaldehyde derivatives

Abstract

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.