Os(II)-catalyzed y-C(sp3)-H amidation and meta-C(sp2)-H alkylation by fine-tuning the characteristics of in-situ-generated C-Os a bonds

Transition metal-catalyzed C-H functionalization has recently emerged as a powerful synthetic tool for accessing various value-added structural motifs. However, addressing the remote C-H acti-vation including y-C(sp3)-H and meta-C(sp2)-H versions is far less investigated and more challenging than that of ortho-C(sp2)-H acti-vation. By fine-tuning the characteristics of the C-osmium (Os) a bond in situ generated by the phenylpyridine scaffold-mediated ortho-C-H activation/C,N-bidentate coordination, either Os(II)-catalyzed intramolecular y-C(sp3)-H amidation or intermolecular meta-C(sp2)-H alkylation has been realized in a highly efficient and chemo-/site-/region-selective manner. Through integrated experi-mental and computational mechanistic studies, the principle of the observed selectivity and two distinct reaction pathways, involving the Os(IV)-nitrenoid-mediated Os(II)-Os(IV)-Os(II) catalytic cycle and the Os(III)-radical-enabled Os(II)-Os(III)-Os(II) SET process, respectively, have been also clarified. Taken together, it provides an insightful reference benchmark for the future development of more wonderful C-H functionalizations mediated by transition metals, especially by less-explored Os.

Automated summary

Transition metal-catalyzed C-H functionalization is a powerful synthetic tool for accessing valuable structural motifs. However, remote C-H activation, such as y-C(sp3)-H and meta-C(sp2)-H versions, is less explored and more challenging than ortho-C(sp2)-H activation. In this study, by fine-tuning the characteristics of osmium bond generated through phenylpyridine scaffold-mediated ortho-C-H activation/C,N-bidentate coordination, highly efficient and selective intramolecular y-C(sp3)-H amidation and intermolecular meta-C(sp2)-H alkylation were achieved. The observed selectivity and reaction pathways were clarified through experimental and computational mechanistic studies. This work provides valuable insights for the future development of C-H functionalizations mediated by transition metals, especially osmium.