Penetrating the Elusive Mechanism of Copper-Mediated Fluoromethylation in the Presence of Oxygen through the Gas-Phase Reactivity of Well-Defined [LCuO]+ Complexes with Fluoromethanes (CH(4–n)Fn, n = 1–3)

Nicole J. Rijs^*†, Patricio González-Navarrete^‡, Maria Schlangen^‡, and Helmut Schwarz^*‡

^‡ Institut für Chemie, Technische Universität Berlin, Straße des 17. Juni 115, 10623 Berlin, Germany

^† Institute of Nanotechnology, Karlsruhe Institute of Technology, Hermann-von-Helmholtz Platz 1, 76344 Eggenstein-Leopoldshafen, Germany

J. Am. Chem. Soc., Article ASAP

DOI: 10.1021/jacs.5b12972

http://pubs.acs.org/doi/abs/10.1021/jacs.5b12972

http://pubs.acs.org/doi/pdf/10.1021/jacs.5b12972

Abstract

Traveling wave ion mobility spectrometry (TWIMS) isomer separation was exploited to react the particularly well-defined ionic species [LCuO]⁺ (L = 1,10-phenanthroline) with the neutral fluoromethane substrates CH_(4–n)F_n (n = 1–3) in the gas phase. Experimentally, the monofluoromethane substrate (n = 1) undergoes both hydrogen-atom transfer, forming the copper hydroxide complex [LCuOH]^•+ and concomitantly a CH₂F^• radical, and oxygen-atom transfer, yielding the observable ionic product [LCu]⁺ plus the neutral oxidized substrate [C,H_3,O,F]. DFT calculations reveal that the mechanism for both product channels relies on the initial C–H bond activation of the substrate. Compared to nonfluorinated methane, the addition of fluorine to the substrate assists the reactivity through a lowering of the C–H bond energy and reaction preorganization (through noncovalent interaction in the encounter complex). A two-state reactivity scenario is mandatory for the oxidation, which competitively results in the unusual fluoromethanol product, CH₂FOH, or the decomposed products, CH₂O and HF, with the latter channel being kinetically disfavored. Difluoromethane (n = 2) is predicted to undergo the analogous reactions at room temperature, although the reactions are less favored than those of monofluoromethane. The reaction of trifluoromethane (n = 3, fluoroform) through C–H activation is kinetically hindered under ambient conditions but might be expected to occur in the condensed phase upon heating or with further lowering of reaction barriers through templation with counterions, such as potassium. Overall, formation of CH_(3–n)F_n^• and CH_(3–n)F_nOH occurs under relatively gentle energetic conditions, which sheds light on their potential as reactive intermediates in fluoromethylation reactions mediated by copper in the presence of oxygen.