Promoting Catalytic C-Selective Sulfonylation of Cyclopropanols against Conventional O-Sulfonylation Using Readily Available Sulfonyl Chlorides

Abstract

Against the backdrop of the well-known O-sulfonylation of cyclopropyl alcohols with sulfonyl chlorides, we examined the feasibility of conducting regioselective C-sulfonylation. By emulating an umpolung strategy-guided design, we report for the first time the Cu(II)-catalyzed β-sulfonylation of cyclopropanols by a mechanism that potentially involves an oxidative addition of a sulfonyl radical to a metal homoenolate. Unlike reported methods, this protocol allows a practical synthetic route to γ-keto sulfone building blocks from cyclopropanols by leveraging commercially available aryl- and alkyl-sulfonyl chlorides, common reagents in organic chemistry laboratories. Using operationally simple open-flask conditions, the preparative scope of starting materials was demonstrated using an array of aryl- and alkyl-substituted sulfonyl chlorides and cyclopropanols (43 examples, up to 96% yield).

Sequential Ring Opening/In Situ SO2-Capture/Alkynylation of Cyclopropanols with Alkynyl Triflones Initiated by Energy Transfer

“…Afterward, a route to γ-keto sulfones via a metal-free reaction of cyclopropanols, DABCO·(SO 2 ) 2 , with alkyl halides or electron-deficient olefins was also described by the same group . Besides that, Subbaiah and co-workers recently presented a Cu­(II)-catalyzed C -selective sulfonylation of cyclopropanols with sulfonyl chlorides . Although the excellent results were documented, developing simple, general, and ecofriendly protocols for the assembly of γ-keto sulfones with versatile functionalities, which should be of great value for organic synthesis and medicinal chemistry, is still in high demand.…”

Copper-Catalyzed 1,2-Sulfonyletherification of 1,3-Dienes

“…For example, dapsone (4,4′-diaminodiphenyl sulfone) is used to kill Mycobacterium leprae ; apremilast is an antipsoriatic drug, and bicalutamide is an anti-prostate cancer drug . Therefore, the development of straightforward, mild, and efficient strategies for the synthesis of sulfone-containing compounds has been a focus and hot topic in organic synthesis . Direct sulfonylation functionalizations of structurally versatile 1,3-dienes would be a viable strategy for accessing highly functionalized sulfones .…”