Theoretical Studies On The Cu-Catalyzed C–H Functionalization

Selective C–H functionalization is proved to be the most step-efficient and straightforward methods to construct heterocycles. In contrast, the Cu-catalyzed/mediated annulation reaction through C–H activation has been considered as a green atom-economic, cost-effective and low-toxic coupling reaction. It is important that studying the mechanism of Cu-catalyzed C–H activation. In this thesis, the mechanism of Cu-catalyzed C–H activation reactions has been investigated by the density functional theory(DFT). The main contents of this thesis contain two parts as follows:1. The mechanism of Cu(OAc)2-catalyzed C–H activation has been investigated with the B3LYP/6-311+G(d,p). Four possible reaction paths(path 1: N–H/C–H activation; path2: C–H/Cu–H agostic activation; path 3: C–H/N–H activation by coordination of the imine moiety; path 4: N–H/C–H activation) of the copper-catalyzed C–N coupling reactions have been studied through our DFT calculations. It was found that path 4 is kinetically most favorable and the activation barrier of rate-determining steps is 21.36 kcal/mol. That is, electrophilic Cu(OAc)2 species bind to the imine moiety to form imine-coordinated complex, and afford the final product through the rate-determining step of the aromatic C–H activation.2. A metal(Cu and Ag)-cocatalyzed dehydrogenative coupling of arenes with alcohols has been investigated with the B3LYP/6-311+G(d,p). All possible transition states of C–H activation step on the dehydrogenative coupling of arenes with alcohols have been studied.The activation barriers of orth-C–H activation steps from 2-phenylpyridine with 1-butanol to butoxyarene under Cu(OAc)2/Ag OTf catalysis were calculated. Among all the transition states of orth-C–H activation step investigated, Cu(OAc)2 conjunction with Ag OTf was found to be kinetically most favorable. The activation energy is 21.36 kcal/mol. On the other hand, the selectivety of the reaction involved in the C–H activation step was also explored while 2-benzylpyridine was reacted with HOBu. The activation barriers of aromatic C–H Activation of 2-phenylpyridine is higer than benzylic C–H activation. The computed activation energy difference between these two transition states(C–H activation steps) is 1.37 kcal/mol. That is to say, benzylic C–H activation is kinetically easier than aromatic C–H activation.