Role of Bronsted Acids in Promoting Pd(OAc)2-Catalyzed Chlorination of Phenol Carbamates Using N-Chlorosuccinimide

Numerous studies have demonstrated that Bronsted acids (HAs), such as HOTf and HOTs, can promote Pd(OAc)(2)-catalyzed functionalization of C-H bonds. However, the rationale for using these acids as a promoter is not yet completely obvious. The purpose of this work is to provide a detailed explanation for this observation with the aid of density functional theory calculations. This is accomplished by investigating the chlorination mechanism of phenol carbamates (DG similar to C-H) with N-chlorosuccinimide (NCS) using HOTf as a promoter and Pd(OAc)(2) as a catalyst. Typically, in order for Pd(OAc)(2) to activate the C-H bond, it is believed that the trinuclear precatalyst Pd-3(OAc)(6) reacts with the substrate DG similar to C-H to generate the chelated complex [Pd(OAc)(2)(DG similar to C-H)], from which C-H activation occurs via a concerted metalation-deprotonation mechanism. Because the substrate DG similar to C-H binds relatively weak to palladium, the corresponding chelated complex lies much higher in energy than the reference structure Pd-3(OAc)(6), resulting in a very high energy barrier for C-H activation. The Bronsted acid HA is capable of undergoing ligand-exchange reactions with both Pd-3(OAc)(6) and [Pd(OAc)(2)(DG similar to C-H)] to form Pd-3(OAc)(6-x)(A) x and [Pd(OAc)(A)(DG similar to C-H)], respectively. Our calculations demonstrate that while the formation of [Pd(OAc)(A)(DG similar to C-H)] from [Pd(OAc)2(DG similar to C-H)] is highly exergonic, that of Pd-3(OAc)(6-x)(A)(x) from Pd-3(OAc)(6) is either nearly thermoneutral or endergonic. This feature significantly reduces the energy difference between the reference structure and the chelated complex, resulting in a significant decreased energy barrier for C-H activation. We also found that the acidity of the employed HA influences the energy difference between the trinuclear reference structure and the chelated complex [Pd(OAc)(A)(DG similar to C-H)]; the more acidic the HA, the smaller the energy difference, and the lower the activation energy of C-H activation. In addition, our calculations show that the presence of HA not only lowers the overall energy barrier for C-H activation but also accelerates the chlorination step by protonating one of the oxygen atoms in NCS rather than the N atom.

Automated summary

This study provides a detailed explanation for the observation that Bronsted acids can promote Pd-catalyzed functionalization of C-H bonds. Density functional theory calculations show that the presence of Bronsted acid reduces the energy barrier for C-H activation, leading to accelerated reactions.