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

Abstract

Numerous studies have demonstrated that Brønsted 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∼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 Pd3(OAc)6 reacts with the substrate DG∼C-H to generate the chelated complex [Pd(OAc)2(DG∼C-H)], from which C-H activation occurs via a concerted metalation-deprotonation mechanism. Because the substrate DG∼C-H binds relatively weak to palladium, the corresponding chelated complex lies much higher in energy than the reference structure Pd3(OAc)6, resulting in a very high energy barrier for C-H activation. The Brønsted acid HA is capable of undergoing ligand-exchange reactions with both Pd3(OAc)6 and [Pd(OAc)2(DG∼C-H)] to form Pd3(OAc)6-x(A)x and [Pd(OAc)(A)(DG∼C-H)], respectively. Our calculations demonstrate that while the formation of [Pd(OAc)(A)(DG∼C-H)] from [Pd(OAc)2(DG∼C-H)] is highly exergonic, that of Pd3(OAc)6-x(A)x from Pd3(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∼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. Show more