Mechanism of Rhodium-Catalyzed C–H Functionalization: Advances in Theoretical Investigation

Abstract

Transition-metal-catalyzed cross-coupling has emerged as an effective strategy for chemical synthesis. Within this area, direct C-H bond transformation is one of the most efficient and environmentally friendly processes for the construction of new C-C or C-heteroatom bonds. Over the past decades, rhodium-catalyzed C-H functionalization has attracted considerable attention because of the versatility and wide use of rhodium catalysts in chemistry. A series of C-X (X = C, N, or O) bond formation reactions could be realized from corresponding C-H bonds using rhodium catalysts. Various experimental studies on rhodium-catalyzed C-H functionalization reactions have been reported, and in tandem, mechanistic and computational studies have also progressed significantly. Since 2012, our group has performed theoretical studies to reveal the mechanism of rhodium-catalyzed C-H functionalization reactions. We have studied the changes in the oxidation state of rhodium and compared the Rh(I)/Rh(III) catalytic cycle to the Rh(III)/Rh(V) catalytic cycle using density functional theory calculation. The development of advanced computational methods and improvements in computing power make theoretical calculation a powerful tool for the mechanistic study of rhodium chemistry. Computational study is able to not only provide mechanistic insights but also explain the origin of regioselectivity, enantioselectivity, and stereoselectivity in rhodium-catalyzed C-H functionalization reactions. This Account summarizes our computational work on rhodium-catalyzed C-H functionalization reactions. The mechanistic study under discussion is divided into three main parts: C-H bond cleavage step, transformation of the C-Rh bond, and regeneration of the active catalyst. In the C-H bond cleavage step, computational results of four possible mechanisms, including concerted metalation-deprotonation (CMD), oxidative addition (OA), Friedel-Crafts-type electrophilic aromatic substitution (SAr), and σ-complex assisted metathesis (σ-CAM) are discussed. Subsequent transformation of the C-Rh bond, for example, via insertion of CO, olefin, alkyne, carbene, or nitrene, constructs new C-C or C-heteroatom bonds. For the regeneration of the active catalyst, reductive elimination of a high-valent rhodium complex and protonation of the C-Rh bond are emphasized as potential mechanism candidates. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of rhodium-catalyzed C-H functionalization reactions are also commented upon in this Account. The origin of the selectivity is clarified through theoretical analysis. Furthermore, we summarize and compare the changes in the oxidation state of rhodium along the complete reaction pathway. The work described in this Account demonstrates that rhodium catalysis might proceed via Rh(I)/Rh(III), Rh(II)/Rh(IV), Rh(III)/Rh(V), or non-redox-Rh(III) catalytic cycles.

Rhodium‐Catalyzed C(sp2)‐ or C(sp3)−H Bond Functionalization Assisted by Removable Directing Groups

“…[10,11] On the other hand, the functionalization of C(sp 3 )ÀHb onds is still underdeveloped. [39][40][41] Furthermore,atransient directing group directed C À H functionalization related to this Review was also reviewed by several research groups. Themajor progress made and the clearer understanding of the mechanistic aspects of C À Ha ctivation have also been reviewed.…”

Catalytic Isofunctional Reactions—Expanding the Repertoire of Shuttle and Metathesis Reactions

“…[1] Ther emoval of one of the byproducts through evaporation, precipitation, or even irreversible conversion into asecondary product, is another example of this strategy.F or example,ethylene extrusion is acommon driving force in alkene metathesis reactions (Scheme 2C). As rearrangements, [12,13] isomerizations, [16] transfer hydrogenation, [1] alkene metathesis, [2] and alkyne [3] metathesis are beyond the scope of this Review,i nterested readers are encouraged to consult several other recently published reviews on these topics.A dditionally,o nly examples using homogeneous catalysis will be included. As rearrangements, [12,13] isomerizations, [16] transfer hydrogenation, [1] alkene metathesis, [2] and alkyne [3] metathesis are beyond the scope of this Review,i nterested readers are encouraged to consult several other recently published reviews on these topics.A dditionally,o nly examples using homogeneous catalysis will be included.…”

Katalytische, isofunktionelle Reaktionen – Erweiterung des Repertoires an Shuttle‐ und Metathesereaktionen

“…Am einfachsten ist dies zu erreichen, indem ein Reaktionspartner in hohem Überschuss eingesetzt wird, eine geläufige Strategie in der Tr ansferhydrierung (Schema 2B). Da Umlagerungen, [12,13] Isomerisierungen, [16] Tr ansferhydrierungen [1] und Metathesereaktionen von Alkenen [2] und Alkinen [3] nicht im Rahmen dieses Aufsatzes liegen, werden dem interessierten Leser mehrere kürzlich erschienene Übersichtsartikel nahegelegt. Beispielsweise ist die Freisetzung von Ethen eine übliche Tr iebkraft in Metathesereaktionen von Alkenen (Schema 2C).…”