Microwave-Assisted Proline-Catalyzed Direct Asymmetric Mannich Reaction

Significance

The authors describe a screening of conditions leading to an optimized micro­wave-assisted protocol for the direct asymmetric (S)-proline-catalyzed Mannich reaction employing cyclohexanone (1), formaldehyde (2) and substituted anilines 3 as substrates. Catalyst loadings of less than 1% have been realized under optimized conditions. The reaction time could be decreased from 30 hours to a maximum of 4 hours, still yielding 44-96% of amines 4 after a reduction step, and the enantioselectivity (94-98% ee) is not diminished under these conditions.