2022 journal article

One-Pot Synthesis of Strain-Release Reagents from Methyl Sulfones

Journal of the American Chemical Society, 144(11), 4764–4769.

By: M. Jung  n & V. Lindsay n 

MeSH headings : Butanes; Dimethyl Sulfoxide; Epichlorohydrin; Indicators and Reagents; Sulfones
UN Sustainable Development Goal Categories
Source: ORCID
Added: March 15, 2022

Sulfone-substituted bicyclo[1.1.0]butanes and housanes have found widespread application in organic synthesis due to their bench stability and high reactivity in strain-releasing processes in the presence of nucleophiles or radical species. Despite their increasing utility, their preparation typically requires multiple steps in low overall yield. In this work, we report an expedient and general one-pot procedure for the synthesis of 1-sulfonylbicyclo[1.1.0]butanes from readily available methyl sulfones and inexpensive epichlorohydrin via the dialkylmagnesium-mediated formation of 3-sulfonylcyclobutanol intermediates. Furthermore, the process was extended to the formation of 1-sulfonylbicyclo[2.1.0]pentane (housane) analogues when 4-chloro-1,2-epoxybutane was used as the electrophile instead of epichlorohydrin. Both procedures could be applied on a gram scale with similar efficiency and are shown to be fully stereospecific in the case of housanes when an enantiopure epoxide was employed, leading to a streamlined access to highly valuable optically active strain-release reagents.