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Difluorocarbene Generation from TMSCF<sub>3</sub>: Kinetics and Mechanism of NaI-Mediated and Si-Induced Anionic Chain Reactions

Andrés García‐Domínguez, Thomas H. West, Johann J. Primozic, Katie M. Grant, Craig P. Johnston, Grant G. Cumming, Andrew G. Leach, Guy C. Lloyd‐Jones

2020Journal of the American Chemical Society73 citationsDOIOpen Access PDF

Abstract

The mechanism of CF2 transfer from TMSCF3 (1), mediated by TBAT (2–12 mol %) or by NaI (5–20 mol %), has been investigated by in situ/stopped-flow 19F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation and competing TFE/c-C3F6/homologous perfluoroanion generation, 13C/2H KIEs, LFERs, CF2 transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3 anionoid to TMSCF3 (1) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 (1) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted.

Topics & Concepts

ChemistryKineticsDifluorocarbeneAlkeneReactive intermediateChemical kineticsReaction mechanismComputational chemistryPhotochemistryMedicinal chemistryOrganic chemistryCatalysisQuantum mechanicsPhysicsFluorine in Organic ChemistryInorganic Fluorides and Related CompoundsCyclopropane Reaction Mechanisms
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