Stereospecific Synthesis of Enantioenriched 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 leads to an alkenylcyclopropanol capable of electrophilic activation by N-bromosuccinimide, triggering a regio- and stereospecific 1,2-migration and affording alkylidenecyclobutanones after elimination. Activation of the intermediate with other electrophiles such as HCl or mCPBA leads to the formation of various chiral cyclobutanones and gamma-lactones via alternative pathways.

Automated summary

Sulfonylcyclopropanols are utilized as efficient cyclopropanone equivalents in a formal vinylidene insertion process, leading to the first general synthetic route to enantioenriched alkylidenecyclobutanones. The reaction of an alkenyl-Grignard reagent with N-bromosuccinimide activates the alkenylcyclopropanol for regio- and stereospecific 1,2-migration, resulting in the formation of alkylidenecyclobutanones after elimination. Activation of the intermediate with other electrophiles such as HCl or mCPBA allows for the formation of various chiral cyclobutanones and gamma-lactones through alternative pathways.