Biginelli-like reaction with dialkyl acetone-1,3-dicarboxylates: a remarkable case of steric control

A Biginelli-type condensation is described using dialkyl acetone-1,3-dicarboxylates as active methylene compounds for the preparation of monastrol analogues. Unexpectedly, the reaction with salicylaldehyde formed two different products depending on the ester alkyl group. This product dichotomy was found to be caused by the steric effects exerted by the alcohol terminus of the ester group in the active methylene component. Previous controversial results as to the structure of the Biginelli product 3 are also discussed.