Synthesis of 3,5-disubstituted cyclohex-2-en-1-one via a five-step domino reaction catalyzed by secondary amines: Formation of (e)-α,β-unsaturated methyl ketones

A simple strategy for the synthesis of 5-substituted-3-methylcyclohex-2-en-1-ones by proline-catalyzed five-step domino reactions of acetone and aromatic aldehydes is reported. The starting materials are stirred in the presence of L-proline for 24h then heated to 45°C for a further 4-6h. The method can also be changed to exclusively form α,β-unsaturated methyl ketones with >99% E-selectivity by heating the mixture to 80°C in the second stage.