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

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.