Sulfoximine-Directed Arene ortho-Lithiation

Sulfoximines are an interesting class of compounds, which exhibit Bronsted and Lewis basicity, nucleophilicity, C-H acidity, N-H acidity, hydrogen-bond acceptor capability and chirality. Sulfoximines have received renewed interest in recent times, since incorporation of a sulfoximine group can provide drug candidates with favorable properties. The synthesis and N-H, alpha-C-H and o-C-H functionalization of sulfoximines are currently topics of considerable interest. This Minireview describes the sulfoximine-directed arene ortho-lithiation and the synthesis of ortho-substituted S-aryl sulfoximines. Comparison between the sulfoximine and sulfone group shows that both are equally potent directors in arene ortho-lithiation. Double ortho-lithiation of S-phenyl sulfoximines affords o,o'-dilithiosulfoximines, which undergo a stereoretentive rearrangement to o-sulfinylanilines. S-Phenyl sulfoximines, carrying a alpha-hydrogen atom, are amendable to a selective ortho-lithiation to give o-lithiosulfoximines, which suffer transmetalation to the alpha-lithiosulfoximines at ambient temperatures. Double lithiation of S-phenyl N-H sulfoximines gives access to o,N-dilithiosulfoximines, the reaction of which with biselectrophiles yields bicyclic sulfoximines.

Automated summary

Sulfoximines are a class of compounds with interesting properties such as Bronsted and Lewis basicity, nucleophilicity, C-H acidity, N-H acidity, hydrogen-bond acceptor capability and chirality, which have attracted renewed interest recently for their potential in drug candidates. The synthesis and functionalization of sulfoximines, including arene ortho-lithiation and synthesis of ortho-substituted S-aryl sulfoximines, are currently popular research topics. Comparison with sulfone group shows both groups are equally effective in directing arene ortho-lithiation, with the ability to produce various compounds with different rearrangements and reactions.