Diols Speed Up Guanidine Base Catalyzed Claisen‐Schmidt Condensation to Produce New 15‐Arylidene Steroids

Abstract

AbstractConsiderable acceleration was observed in the guanidine‐base catalysed Claisen‐Schmidt condensation of benzaldehyde and a 17α‐methyl‐18‐nor‐5α,13α‐androstan‐16‐one (1) in the presence of ethylene glycol. Rate‐enhancement effects of various alcohols and diols were compared. In quantum chemical calculations, coordination of the carbonyl group of the substrate was found to reduce the potential barrier to the proton transfer from the α carbon and thus facilitate the formation of the anion that attacks the aldehyde. Both the experiments and the calculations showed that diols enhance the reactivity more efficiently than alcohols. Ethylene glycol/guanidine‐base mixtures were found to be efficient catalysts and solvents in the synthesis of a range of new 17α‐methyl‐18‐nor‐13α‐15‐arylidene steroids. This solvent mixture has a further advantage: the crude products can be isolated by simple extraction after introduction of CO2. It is also shown that by the proper choice of the base, the base/diol mixture can be recycled.