Enantioselective Synthesis of Alkylidenecyclobutanones via Formal Vinylidene Insertion into Cyclopropanone Equivalents


1-Sulfonylcyclopropanols are employed here as efficient cyclopropanone equivalents in a formal vinylidene insertion process, providing the first general synthetic route to enantioenriched alkylidenecyclobutanones. The addition of an alkenyl-Grignard reagent to the cyclo-propanone leads to an alkenylcyclopropanol capable of electrophilic activation by NBS, triggering a regio- and stereospecific 1,2-migration and the formation of a brominated cyclobutanone intermediate prone to elimination. The parent β-amino ketone can also be accessed by one-pot aza-Michael addition to the resulting product, and activation of the alkenylcyclopropanol intermediate with other electrophiles such as HCl or mCPBA led to the controlled formation of a variety of chiral cyclobutanones and γ-lactones via alternative pathways.