Transition-Metal-Free Reductive Cross-Coupling Employing Metabisulfite as a Connector: General Construction of Alkyl-Alkyl Sulfones

A multicomponent reductive cross-coupling of unactivated alkyl halides and alkyl tosylates connected via sodium metabisulfite was established for the general construction of alkyl-alkyl sulfones. Neither a metal catalyst nor a metal reductant is required in this "green" reductive cross-coupling. Inorganic sodium metabisulfite served as both the sulfur dioxide source and the robust connector. Safe formate was used as a highly efficient single-electron reductant. Both intramolecular and intermolecular reductive cross-couplings were achieved with broad substrate scopes. Diverse biologically important molecules were efficiently cross-linked with steroids, saccharides, amino acids, peptides, and pharmaceuticals with sensitive functional groups, affording sulfone-bridged hybrid molecules. Mechanistic studies demonstrated that alkyl radicals were involved in the singly occupied molecular orbital (SOMO) of the metabisulfite salt, initiating the transformation. [GRAPHICS] .