1621256-23-2Relevant articles and documents
Mechanistic Origins of Regioselectivity in Cobalt-Catalyzed C(sp2)-H Borylation of Benzoate Esters and Arylboronate Esters
Chirik, Paul J.,MacMillan, Kaitlyn T.,Pabst, Tyler P.,Quach, Linda
, (2021)
Carbon–hydrogen (C–H) bonds are ubiquitous in organic molecules, and methods for their selective functionalization to more reactive functional groups is a long-standing goal in catalysis, as applied to organic synthesis. Of the established methods involving transition metal catalysts, many employ carefully engineered substrate-catalyst interactions, placing the targeted C–H bond proximal to the metal catalyst, resulting in activation and subsequent functionalization. Here, we report mechanistic investigations describing a conceptual alternative to this approach whereby a cobalt-based borylation catalyst differentiates between subtle electronic differences in C(sp2)-H bonds of benzoate esters and arylboronate esters. These advances motivate studies of catalysts that rely on inherent differences in C–H bond electronics to distinguish chemically inequivalent sites, providing a new tool for organic synthesis. Synthetic and mechanistic investigations into the C(sp2)-H borylation of various electronically diverse arenes catalyzed by bis(phosphine)pyridine (iPrPNP) cobalt complexes are reported. Borylation of various benzoate esters and arylboronate esters gave remarkably high selectivities for the position para to the functional group; in both cases, this regioselectivity was found to override the ortho-to-fluorine regioselectivity, previously reported for (iPrPNP)Co borylation catalysts, which arises from thermodynamic control of C(sp2)-H oxidative addition. Mechanistic studies support pathways that result in para-to-ester and para-to-boronate ester selectivity by kinetic control of B-H and C(sp2-H) oxidative addition, respectively. Borylation of a particularly electron-deficient fluorinated arylboronate ester resulted in acceleration of C(sp2)-H oxidative addition and concomitant inversion of regioselectivity, demonstrating that subtle changes in the relative rates of individual steps of the catalytic cycle can enable unique and switchable site selectivities. Most strategies to selectively activate and functionalize a specific C–H bond in an organic molecule rely upon carefully engineered spatial interactions between a substrate and a transition metal catalyst. Here, we report a conceptually distinct alternative strategy, whereby a cobalt catalyst distinguishes between subtly different C(sp2)-H sites of an arene based on electronics rather than sterics. Mechanistic studies elucidated the origins of substrate-controlled regioselectivity in the C(sp2)-H borylation of benzoate esters and arylboronate esters.
