Rh^III‐Catalyzed C(sp³)H Bond Activation by an External Base Metalation/Deprotonation Mechanism: A Theoretical Study

Abstract

The C(sp(3) )H bond activation of 8-methylquinoline followed by alkyne insertion catalyzed by a Rh(III) complex has been studied by using density functional theory (DFT) calculations. Contrary to common belief, the CH bond activation of methylquinoline does not occur by the traditional intramolecular concerted metalation/deprotonation (CMD) mechanism but by an external base CMD mechanism. The use of free acetate or copper(II) acetate as base permits the CH activation step, as observed experimentally. However, the following insertion is possible only if copper(II) acetate is used. The insertion followed by metathesis occurs via a cationic Rh(III) complex and is irreversible, which ensures the efficiency of the entire process. Therefore the use of copper is crucial for completing the catalytic cycle. The present work should help to rationalize the origins of the experimental results described in the literature.

Theoretical Investigation of Regioselectivity in the Rh‐Catalyzed Coupling Reaction of 3‐Phenylthiophene with Styrene

“…Enthalpies were calculated using the unscaled vibrational frequencies. Several authors have pointed out issues with the entropy contribution to the change in the Gibbs energy of the reaction by the PCM solvation model . Therefore, in this study, enthalpy was preferred as the primary tool for describing reactions in solution.…”

Thioamide‐Directed Cobalt(III)‐Catalyzed Selective Amidation of C(sp3)−H Bonds

“…This result supports the observed selective C−H amidation at the primary methyl group of the thioamide. The cyclometalation in complex C then leads to intermediate D , potentially by an external carboxylate‐assisted concerted metalation/deprotonation (CMD‐ext) mechanism . The activation barrier for CMD‐ext was determined to be lower (Δ G ≠ 298 =4.5 kJ mol −1 ) than the traditional intramolecular concerted metalation/deprotonation (CMD‐int) (Δ G ≠ 298 =40.9 kJ mol −1 ) thus favoring the former.…”

Computational Characterization of the Mechanism for the Oxidative Coupling of Benzoic Acid and Alkynes by Rhodium/Copper and Rhodium/Silver Systems

“…Despite the many experimental advances, the theoretical background of oxidative couplings is still in the early stages, as substantial advances in catalytic cycles for cross‐coupling catalytic cycles and in metal‐catalyzed C−H activation have not yet found full translation. The computational study of oxidative coupling has focused mainly on the influence of acetate ligands in the C−H activation step (via a CMD transition state) . Some catalytic cycles have only been reported for rhodium‐catalyzed oxidative couplings, such as internal oxidant‐controlled reactions, an intramolecular version of alkyne coupling to a benzamide, and a comprehensive study of heterocycle synthesis in which selectivity issues were also addressed .…”

“…The computational study of oxidative coupling has focusedm ainly on the influence of acetate ligandsi nt he CÀHa ctivation step (via aC MD transition state). [18] Some catalytic cycles have only been reported for rhodium-catalyzed oxidative couplings, such as internal oxi-dant-controlled reactions, [19] an intramolecular version of alkyne coupling to ab enzamide, [20] and ac omprehensive study of heterocycle synthesis in which selectivity issues were also addressed. [21] In these previous works, [CpRh(OAc) 2 ]w as assumed to be the active species, which is not clear in the presence of coppera cetate as the oxidant.…”