Observing the Agostic Hydrogen in Pd(II)-Catalyzed Aromatic C–H Activation

Abstract

Direct C−H activation and functionalization offer a convenient protocol for pharmaceutical and material syntheses. Although versatile mechanisms have been proposed to depict transition-metal-catalyzed C−H activation, to date, the shared key agostic hydrogen intermediate in several major mechanisms has not been observed yet, which apparently puzzles the mechanism-based catalyst design. This work reports the direct observations of this intermediate in Pd(II)/Sc(III)-catalyzed C−H activation of acetanilides, and its stability and reactivity in C−H activation are investigated. Remarkably, this intermediate is only observed in electron-rich acetanilides, and the metasubstituent with increased σ m constant generally accelerates C−H activation, a characteristic of the base-assisted C−H activation mechanism. This study has unveiled the masks of this intermediate with an understanding of its first-hand physicochemical properties, shedding new light on mechanism-based catalyst design.

Pd(II)/Lewis Acid Catalyzed Intramolecular Oxidative C−H Amination to Construct Carbazoles with Dioxygen

“…Remarkably, the H/D exchange also resulted in 44 % deuterium incorporation at the ortho position of the aniline ring, which can be attributed to the carbonyl moiety of the − N Ac group serving as the directing group in C−H activation as well as those in literature [22] . As evidence, a carbonyl moiety of the − N Ac group ligated palladacycle compound was even isolated with X‐ray characterizations in Pd(II)/Sc(III)‐catalyzed C−H activation of acetanilides in our previous studies [9] . Unexpectedly, the H/D exchange was also observed at the meta position of this aniline ring, giving a 4 % deuteration ratio, which may be attributed to the remote C−H activation of the aniline ring [6f,23] .…”

“…[22] As evidence, a carbonyl moiety of the À NAc group ligated palladacycle compound was even isolated with Xray characterizations in Pd(II)/Sc(III)-catalyzed CÀ H activation of acetanilides in our previous studies. [9] Unexpectedly, the H/D exchange was also observed at the meta position of this aniline ring, giving a 4 % deuteration ratio, which may be attributed to the remote CÀ H activation of the aniline ring. [6f,23] This phenomenon was much clearer by using 1 w as the substrate, which gave a 64 % deuteration ratio at the ortho position with a 36 % deuteration ratio at the meta position of the aniline ring (Scheme S1).…”

“…So far, this catalysis has been applied in a list of organic syntheses, [6] including one most recent work on oxidative C−H olefination/annulation to construct dihydrophenanthridines, [7] and expanded to Ni(II)/LA catalyzed S−P bond formation [8] . Particularly, in these Pd(II)/LA catalysis, versatile intermediates from different reactions, including the long‐missing agostic hydrogen intermediate in aromatic C−H activation, were identified through in situ NMR characterizations which provided multiple mechanistic information for Pd(II) catalysis [6i,j,9] . Remarkably, dioxygen was generally employed as the sole oxidant in those oxidation‐involved syntheses which makes them more applicable.…”

Nickel(ii)/Lewis acid catalysed olefin hydroamination and hydroarylation under mild conditions

“…Due to the paramagnetic effect of the Ni 2+ Table 3 Substrate scope for Ni(II)/Sc(III)-catalysed hydroamination reaction of electron-deficient olefins with anilines a cation, the 1 H-NMR studies of the Ni(OAc) 2 /Sc(OTf ) 3 catalyst were not able to be carried out, which was different from the Pd(II)/LA catalysts. [27][28][29]31,32 However, in our previous studies on a Ni(OAc) 2 /Y(OTf ) 3 catalysed oxidative S-P bond formation reaction, 36 a heterobimetallic [Ni(OAc) 2 /Y(OTf ) 2 (DMF) 2 ] + cluster in DMF was identified by HRMS, which led us to propose a diacetate bridged Ni(II)/Y(III) core as the key active species for catalysis 36 as well as the similar diacetate bridged heterobimetallic core for the Pd(II)/LA catalysis. Herein, a slight but not ignorable blue-shift of the Ni(OAc) 2 band in TFE was also observed by adding 1 equiv.…”

“…Inspired by the finding of the LA promoted Wacker-type oxidations by Pd(OAc) 2 in our previous studies, which were even more efficient than Pd(II)/Cu(II) oxidation, 26 we outlined the Pd (II)/LA catalysis pathway for use in organic synthesis. This Pd (II)/LA catalysis could not only be applied in versatile Pd(II)-catalysed syntheses by aromatic C-H activation with dioxygen as the sole oxidant, [27][28][29][30][31][32][33] it could also be applied in nitrile hydration with water and alkyne oxidation with DMSO, in which Pd(II)/LA functioned as the Lewis acid catalyst. 34,35 In this Pd(II)/LA catalysis, the linkage of the LA to the Pd(II) species by a diacetate bridge sharply improved its catalytic efficiency.…”