Abnormal Michael Reaction: Condition-Dependent Product Distributions in the Michael Reaction of Monoalkyl-Substituted Malonates

The abnormal Michael reaction reported by Thorpe and Michael in 1900, which involves the transfer of an activating group from a nucleophilic species to an α-carbon of the Michael acceptor in reaction with monosubstituted malonates, was revisited using prototypical substrates for both intramolecular and intermolecular reactions. In both reactions, condition-dependent product distributions were observed. Thus, under the conditions using NaHMDS or NaH in THF or Et2O, no formation of the abnormal Michael product was observed, and the major product was an apparent retrograde Michael reaction in the abnormal Michael product resulting from an elimination of a malonate anion with the migrated acyl group as a part of it. The use of a base capable of generating a proton source such as NaOEt resulted in formation of the abnormal Michael product in the intermolecular reaction, although the retrograde Michael product was still a major product. On the other hand, in the intramolecular reaction, the abnormal product was not detected under any conditions used. A plausible reaction mechanism in which the lower kinetic acidity of the malonate proton compared to the thermodynamic acidity plays a significant role has been proposed.