Reductive Cross-coupling For The Construction Of Sulfones

Sulfones play a prominent role in organic and medicinal chemistry.Not only are they wide range of applications in pharmaceutical and agrochemical are known,but they are versatile intermediates in organic synthesis.Therefore,it is of great significance to develop efficient and green methods to construct sulfones.Our group has been developing the application of inorganic sulfur dioxide source to construct sulfones,and we will continue to follow this strategy and combine the method of reductive cross-coupling to straightforward construction of diversely functionalized sulfones.Part Ⅰ:Construction of Aryl Alkyl SulfonesAn efficient and practical multicomponent reductive cross-coupling involving an inorganic salt（sodium metabisulfite）for the synthesis of sulfones through a simple combination of aryl iodide and alkyl bromide have been developed.Both the intermolecular and intramolecular（five-to twelve-membered cyclic sulfones）reductive cross-couplings were fully explored and provided facile access to a wide range of sulfones from the corresponding alkyl and aryl halides.Naturally occurring biomolecules,such as steroids,saccharides,and amino acids,were highly compatible with this multicomponent reductive cross-coupling.Four drug molecules were efficiently prepared via late-stage SO₂ insertion.Mechanistic studies demonstrated that alkyl radicals and sulfonyl radicals were involved in this transformation.Part Ⅱ:Construction of Alkyl Alkyl SulfonesAn efficient and practical multicomponent reductive cross-coupling involving an inorganic salt（sodium metabisulfite）,green and cheap potassium formate as reducing agent for the synthesis of sulfones through a simple combination of alkyl tosylates and alkyl iodides have been developed.There was no metal involed in the whole transformation and a multicomponent reductive cross-coupling for the straightforward construction of sulfones.The cross-coupling was found to proceed under mild conditions and was able to tolerate a diverse set of functional groups.