Lactamization of sp(2) C-H bonds with CO2 under transition-metal-free and redox-neutral conditions: a computational mechanistic study

摘要

The detailed mechanism for the lactamization of sp(2) C-H bonds in aniline with CO2 to 2-quinoline under transition-metal-free and redox-neutral conditions was studied by density functional theory (DFT) calculations. Among all the examined reaction pathways over the base, we found that the minimum energy reaction pathway (MERP) consists of three stages: (i) the reaction of aniline and CO2 to generate the sodium salt of carbamate (NaCA), (ii) the deoxygenation of the NaCA species to form the isocyanate intermediate, and (iii) the intramolecular cyclization of the isocyanate group to the sp(2) C-H bond. Overall, the deoxygenation of the NaCA species in stage (ii) is rate-determining for the entire reaction. The base plays a significant role in reducing the energy barriers for the formation of the NaCA species and the intramolecular cyclization of the isocyanate group to the sp(2) C-H bond. The free CO2 serves as the atomic oxidant [O] acceptor in the concept of CO2 = CO + O' proposed for the carbonylation reaction. In addition, the calculations disclose that the intermolecular addition of the tert-butanol ((HOBu)-Bu-t) intermediate or substrate aniline to the isocyanate intermediate is kinetically competitive with the intramolecular electrophilic cyclization of the isocyanate group to the sp(2) C-H bond, which successfully accounts for the experimental detection of the tert-butyloxy carbonyl (Boc) protected amide (Boc-amide) and urea intermediates in the reaction mixture. As the base cannot be regenerated along with the formation of the final product, it is predicted that weak basic species like Na2CO3 or NaHCO3 in the reaction system might be effective in promoting the reaction as well. This finding provides a rational interpretation of the experimental observation that the excess of base and high temperature are necessary for the high efficiency of the reaction.