Sulfones represent privileged structural motifs in pharmaceuticals and bioactive molecules. Despite advances in constructing C(sp3)-SO2 bonds via sulfonyl anions or radicals, enantiocontrol remains a formidable challenge. Herein, we disclose a novel asymmetric radical α-sulfonylation strategy utilizing a TBPB/NaI oxidative system catalyzed by chiral N,N'-dioxide-Mg(II) or -Fe(II) complexes. This method enables efficient asymmetric α-sulfonylation of not only β-ketoamides but also dearomative sulfonylation of 2-naphthols with sodium sulfinates under mild conditions for the first time, delivering chiral α-sulfonyl carbonyl compounds in good yields with excellent enantioselectivities and broad substrate scope. Mechanistic studies support a sulfonyl radical addition pathway, wherein the use of TBPB/NaI under basic conditions leverages the oxidative process by the formation of sulfonyl iodide in situ as a radical reservoir, effectively suppressing background reactions and byproduct formation. Meanwhile, the chiral Lewis acid catalyst facilitates the enantioselective radical addition to enol intermediates and the SET process in the case of the iron-involved process. This work offers a new paradigm for achieving enantiocontrol in radical sulfonylation reactions.
Li et al. (Thu,) studied this question.