Mechanisms of Molecular Oxygen-mediated Selective Hydroxyalkylation and Alkylation of Quinoxalin-2(1H)-ones with Alkylboronic acid: A DFT Investigation

Abstract

The mechanisms for the molecular oxygen-mediated selective hydroxyalkylation and alkylation of quinoxalin-2(1H)-ones with alkylboronic acids have been investigated with the M06-2X-D3/ma-def2-SVP method and basis set. The SMD (solvation model based on solute electron density) model was applied to simulate the solvent effect. In the first and second reactions, isopropylboronic acid and O 2 would primarily interact with each other to get isopropyl radical (M2); then it reacts with protonated 1-methylquinoxalin-2(1H)-one (R2-H + ) to get the product derivative. And the favorable path is that the product derivative goes through hydrogen atom transfer (HAT) and proton transfer to yield P1 (or Ps1) in sequence. However, the Gibbs free energy profiles conclude that the R1+R2→P1 process releases much energy in the solvent of acetone in the first reaction and P1 can be yielded in large amount; while in the second reaction, when the solvent becomes acetone from acetonitrile, the Rs1+Rs2→Ps1 process is also an exothermic reaction. But only 10.4 kcal/mol energy would be released and the reverse reaction (Ps1→Rs1+Rs2) with the energy barrier of 31.5 kcal/mol could happen in the temperature of 120 ℃. Moreover, Ps1 could continue to go through a series of reactions (HAT, C-O bonding, homolysis, HAT) to yield the final product P2. Furthermore, the Ps1→P2 process release much more energy (66.8 kcal/mol) and the energy barrier of reverse reaction is so higher that it cannot happen. These factors told us that product P2 can be yielded with large amount an can be existed in the second reaction. The electron spin density maps can help us to understand the single electron transfer process. All the calculations agree with the experimental results. We hope that these results are of great benefit to understand similar reactions between quinoxalin-2(1H)-ones and alkylboronic acids.