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

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1195-1204
Number of pages10
JournalJournal of Organic Chemistry
Volume82
Issue number2
DOIs
StatePublished - Jan 20 2017

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Chemical activation
Acidity
Catalysis
Methanol
Trifluoroethanol
Ligands
Deuterium
Cyclization
Substrates
Density functional theory
Protons
Acetates
Tuning
Catalysts
Experiments
pyridine

Cite this

Mechanistic Study of Cp∗CoIII/RhIII-Catalyzed Directed C-H Functionalization with Diazo Compounds. / Qu, Shuanglin; Cramer, Chris.

In: Journal of Organic Chemistry, Vol. 82, No. 2, 20.01.2017, p. 1195-1204.

Research output: Contribution to journalArticle

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AB - 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.

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