Abstract
A palladium-catalysed aminosulfonylation process is used as the key-step in a one-pot, three-component sulfone synthesis. The process combines aryl-, heteroaryl- and alkenyl iodides with a sulfonyl unit and an electrophilic coupling fragment. The sulfonyl unit is delivered in the form of an aminosulfonamide, which then serves as a masked sulfinate. The sulfinate is combined, in situ, with an electrophilic coupling partner, such as a benzylic, allylic or alkyl halide, an electron-poor arene, or a cyclic epoxide, to provide the corresponding sulfone products in good to excellent yields. The mild reaction conditions and use of commercially available reaction components allows the easy preparation of a broad range of sulfones featuring a variety of functional groups. The process obviates the need to employ thiol starting materials, and oxidative operations.
Highlights
The distinctive structural and electronic features present in sulfones have resulted in these unique functional groups being imbedded in a number of important pharmaceutical and agrochemical molecules
Despite the limitations presented above, sulfone synthesis based on the combination of a sul nate anion with a carboncentered electrophile remains a potentially attractive route to these valuable molecules, due in particular to the wide range of electrophiles that can be employed successfully.[4,7]
We were aware of a number of reports that had demonstrated the effective formation of metal sul nates from a variety of N-aminosulfonamide derivatives; for example, Dornow and Bartsch had shown that N,N0,N0-trialkyl aminosulfonamides could be converted into sodium sul nates under the action of sodium isopropoxide at ambient temperature (3 / 4, Scheme 2).[8]
Summary
The distinctive structural and electronic features present in sulfones have resulted in these unique functional groups being imbedded in a number of important pharmaceutical and agrochemical molecules. Molecules used against medical indications as diverse as migraine and prostate cancer, or as the herbicides mesotrione and cafenstrole, all feature aryl sulfone units (Scheme 1).[1] The variety of chemical reactivity possible with a sulfone group means that they serve as versatile intermediates. Despite the limitations presented above, sulfone synthesis based on the combination of a sul nate anion with a carboncentered electrophile (for example, 1 / 2, Scheme 2) remains a potentially attractive route to these valuable molecules, due in particular to the wide range of electrophiles that can be employed successfully.[4,7] We believed the main challenge in delivering a more useful variant of these transformations was to develop a sul nate based route that avoids the necessity of a sulfonyl chloride intermediate, and the use of harsh reaction conditions.
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