TY - JOUR
T1 - Difluorocarbene Generation from TMSCF3: Kinetics and Mechanism of NaI-Mediated and Si-Induced Anionic Chain Reactions
AU - García-Domínguez, Andrés
AU - West, Thomas H.
AU - Primozic, Johann J.
AU - Grant, Katie M.
AU - Johnston, Craig P.
AU - Cumming, Grant G.
AU - Leach, Andrew G.
AU - Lloyd-Jones, Guy C.
N1 - Funding Information:
A.G.-D. thanks the SNSF for a postdoctoral fellowship (P2ZHP2_181497). C.P.J. thanks the EC for an International Outgoing Fellowship (PIOF-GA-2013–627695). J.J.P. thanks the Bayer Science & Education Foundation, the Deutschlandstipendium, and the Erasmus+ Traineeships Program. The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013)/ERC grant agreements nos. [340163] and [838616].
Publisher Copyright:
© 2020 American Chemical Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/8/13
Y1 - 2020/8/13
N2 - 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.
AB - 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.
U2 - 10.1021/jacs.0c06751
DO - 10.1021/jacs.0c06751
M3 - Article
SN - 0002-7863
VL - 142
SP - 14649
EP - 14663
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 34
ER -