Recent Advances in Theoretical Studies on Transition-Metal-Catalyzed Carbene Transformations

-heterocyclic carbenes as ligands, metal carbene insertion into σ bonds, cyclopropanations, ylide formation, and so forth. The remarkable progress achieved in synthetic chemistry, in turn, has increased the demand for mechanistic studies of carbene chemistry. A thorough understanding of reaction mechanisms can extend the application scope of metal carbene compounds and inspire the rational design of new carbene transformation reactions.Density functional theory (DFT) calculations have been performed in our group to gain more mechanistic insights into metal carbene-related reactions. This account focuses on computational studies of transition-metal-catalyzed carbene transformation reactions with nucleophiles. The generation of metal carbene or metal-ligated free carbene and subsequent carbene transformation pathways is discussed. According to our mechanistic studies of carbene transformation with nucleophiles, three generalized reaction models are summarized, including the intramolecular migratory insertion of metal carbene, intermolecular nucleophilic addition toward metal carbene, and outer-sphere nucleophilic addition to the metal-ligated free carbene.In general, the intermolecular nucleophilic addition mechanism is commonly proposed since metal carbene has an electrophilic carbene carbon. From a mechanistic point of view, the intramolecular migratory insertion mechanism is also widely used because metal carbene insertion into σ bonds formally occurs through this mechanism. An outer-sphere nucleophilic addition mechanism is proposed for reactions that form a metal-ligated free carbene complex instead of the commonly proposed metal carbene. The metal-ligated free carbene complex contains a naked carbene carbon that is not coordinated with the metal center. In this case, a transition-metal catalyst is used only as a Lewis acid, and nucleophilic addition occurs directly at the free carbene carbon. Our computational results suggested that outer-sphere nucleophilic addition is a facile step because metal ligation could stabilize the transition state as well as the generated intermediate. The intramolecular migratory insertion mechanism also has a low energy barrier due to the lack of an entropy penalty. Carbene formation from carbene precursors is usually the rate-determining step, except in intermolecular nucleophilic addition, and the reactivity of nucleophiles has a significant influence on the overall reaction rate. We can also envision that the weak nucleophilicity of nucleophiles would suppress outer-sphere nucleophilic addition. These computational studies showcase the characteristics of three carbene transformation models, and we hope that it will spur the development of mechanistic studies of carbene chemistry.