Proton or Metal? The H/D Exchange of Arenes in Acidic Solvents

Abstract

The H/D exchange of arenes in acidic media by transition-metal and main-group-metal complexes and common inorganic salts was studied. The influence of Lewis acidity, anions, charge, and ligands was evaluated. The results indicate that the determination of H/D exchange activity in acidic media is not related to the formation of metal−carbon bonds (i.e., C−H activation). The combined experimental data (regioselectivity, activation energy, kinetics, isotope effects, solvent effects) and DFT calculations point toward a proton catalysis mechanism. Thus, highly Lewis acidic metal compounds, such as aluminum(III) triflate, were extraordinarily active for the H/D exchange reactions. Indeed, the degree of H/D exchange reactivity allows for a comparative measurement of Lewis acidities.

New Trends in Oxidative Functionalization of Carbon–Hydrogen Bonds: A Review

“…Finally, the term "C´H activation" refers to a metal-mediated pathway involving the formation of metal-carbon bonds [19].…”

Electrophilic RhI catalysts for arene H/D exchange in acidic media: Evidence for an electrophilic aromatic substitution mechanism

“…We propose three possible rationalizations for increased efficacy for benzene/trifluoroacetic acid-d 1 H/D exchange using Rh complexes with electron-withdrawing substituents on the DAB ligand: 1) The C-H activation occurs at the Rh I oxidation state, and less donating ligands stabilize Rh I in the presence of oxidizing trifluoroacetic acid whereas more donating ligands result in oxidation to Rh III ; 2) the C-H activation occurs by an electrophilic substitution process (regardless of the exact mechanism, which could be "classic" electrophilic substitution, see Scheme 1, or concerted-metalation deprotonation) [81] and is enhanced by less electron-rich Rh catalysts; 3) the C-H "activation" occurs by an electrophilic aromatic substitution pathway, as we have previously demonstrated for other metals in acidic media [64], and more electrophilic Rh complexes enhance reactivity. We have no evidence that the DAB-Rh I complexes are oxidized in the presence of trifluoroacetic acid.…”

“…The recent report that Lewis acids can facilitate H/D exchange between arenes and acidic media complicates analysis of transition metal-mediated C-H activation [64]. Thus, we sought a method to generate active catalysts in situ without the use of an additive Lewis acid, such as AgX.…”

“…The regioselectivity of the reactions was determined using 1 H NMR spectroscopy (eq 2). For reactions with toluene, electrophilic aromatic protonation mechanisms favor the ortho and para positions whereas organometallic complexes often favor activation of the meta and para positions [64,82]. The Rh complexes (0.5 mol % relative to toluene-d 8 ) were heated (120 °C, 150 °C, or 180 °C) in trifluoroacetic acid with toluene-d 8 .…”

Trifluoromethanesulfonic Acid as Acylation Catalyst: Special Feature for C- and/or O-Acylation Reactions

“…A study that used a D2O/D2SO4 system found that conditions will lead to either partial or complete racemization of phenylalanine H/D exchange, which is indicated by the exchange of α-protons [79]. Deuterated TFA (TFA-d) is appropriate for slow H/D exchange [80], TfOD catalysis of the direct C-acylation of toluene 118 and glutamic acid derivatives 66b has been previously established (Scheme 16) [74]. The deuterium incorporation was observed only on the aromatic protons (68%-75% deuterium incorporation) at a fine yield (94%) of the acylated product 119.…”