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.