Wednesday, November 8, 2017

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

Mechanism of Rhodium-Catalyzed CH Functionalization: Advances in Theoretical Investigation

Xiaotian Qi,§ Yingzi Li,§ Ruopeng Bai, and Yu Lan*

Acc. Chem. Res. ASAP


Transition-metal-catalyzed cross-coupling has emerged as an effec- tive strategy for chemical synthesis. Within this area, direct CH bond transformation is one of the most efficient and environmentally friendly processes for the construction of new CC or Cheteroatom bonds. Over the past decades, rhodium-catalyzed CH functionalization has attracted considerable attention because of the versatility and wide use of rhodium catalysts in chemistry. A series of CX (X = C, N, or O) bond formation reactions could be realized from corresponding CH bonds using rhodium catalysts. Various experimental studies on rhodium-catalyzed CH function- alization 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 CH 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 CH functionalization reactions.
This Account summarizes our computational work on rhodium-catalyzed CH functionalization reactions. The mechanistic study under discussion is divided into three main parts: CH bond cleavage step, transformation of the CRh bond, and regeneration of the active catalyst. In the CH bond cleavage step, computational results of four possible mechanisms, including concerted metalationdeprotonation (CMD), oxidative addition (OA), FriedelCrafts-type electrophilic aromatic substitution (SEAr), and σ-complex assisted metathesis (σ-CAM) are discussed. Subsequent transformation of the CRh bond, for example, via insertion of CO, olefin, alkyne, carbene, or nitrene, constructs new CC or Cheteroatom bonds. For the regeneration of the active catalyst, reductive elimination of a high-valent rhodium complex and protonation of the CRh bond are emphasized as potential mechanism candidates. In addition to detailing the reaction pathway, the regioselectivity and diastereoselectivity of rhodium-catalyzed CH 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.