Cascade Reactions Directed by Polarity

Significance

A polarity-directed organocatalytic cascade reaction of two different aldehydes with nitromethane in biphasic systems is reported. Since the involved aliphatic aldehydes exhibit similar reactivities, the predominantly formed cross-products of the reaction can be explained by slight differences in polarity. Most likely the proline (1)-catalyzed condensation of the more polar aldehyde with nitromethane succeeds first in the aqueous phase, thus releasing a nitroalkene intermediate. This species enriches in the organic phase consisting of the neat aldehydes, where it undergoes conjugate addition preferred with the less polar aldehyde, accelerated by secondary amine catalyst 2, respectively.