Enantioselective Synthesis of Alkylidenecyclobutanones via Formal Vinylidene Insertion into Cyclopropanone Equivalents

29 June 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


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.


ring expansion


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.