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Mechanistic Study of Cp*CoIII/RhIII-Catalyzed Directed C–H Functionalization with Diazo Compounds

Qu, Shuanglin, Cramer, Christopher J.
Journal of organic chemistry 2017 v.82 no.2 pp. 1195-1204
Lewis bases, acetates, acetonitrile, acidity, carbon-hydrogen bond activation, catalysts, catalytic activity, chemical bonding, chemical reactions, cobalt, diazo compounds, ligands, methanol, methodology, moieties, organic chemistry, pyridines, solvents
Density functional theory calculations have been performed to provide mechanistic insight into a series of Cp*Coᴵᴵᴵ- and Cp*Rhᴵᴵᴵ-catalyzed directed C–H bond functionalizations with diazo-compound substrates. Co-based catalysis proceeds through five steps: C–H bond activation; C–C coupling via a concerted 1,2-aryl transfer; proto-demetalation; nucleophilic addition; and solvent-assisted methanol elimination. C–H bond activation is predicted to be reversible, consistent with deuterium-scrambling experiments. The higher Lewis acidity of Co compared to Rh for two otherwise identical catalysts increases the susceptibility of a coordinated carbonyl group to nucleophilic addition in the former, facilitating the formation of cyclized products not observed for Rh. Methanol elimination is predicted to be the turnover-limiting step for one substrate, and this is facilitated by solvent 2,2,2-trifluoroethanol (TFE) acting as a proton shuttle. Theory suggests that further tuning of acidity may offer opportunities for improving catalysis. We also assess the role of a pyridine group that leads to a different series of final steps in one Rh-based catalytic cycle, thereby enabling access to the otherwise suppressed cyclization product. Our study of an alternative Rh-based system having acetate ligands replaced with MeCN indicates that C–H bond activation is sensitive to those ligands and variation can affect which step is turnover-limiting.