Mechanisms of molecular-oxygen-mediated selective hydroxyalkylation and alkylation of quinoxalin-2(1H)-ones with alkylboronic acid: a DFT investigation

Abstract

The mechanisms of the molecular-oxygen-mediated selective hydroxyalkylation and alkylation of quinoxalin-2(1H)-ones with alkylboronic acids have been investigated using the M06-2X-D3/ma-def2-SVP method and basis set. The SMD (solvation model based on solute electron density) was applied to simulate the solvent effect. In both these reactions, isopropylboronic acid and O₂ first interact with each other to produce an isopropyl radical (M2), which then reacts with protonated 1-methylquinoxalin-2(1H)-one (R2-H⁺) to provide the product derivative. The most favorable path is that in which the product derivative undergoes hydrogen atom transfer (HAT) and proton transfer to yield P1 (or Ps1) in sequence. However, the Gibbs free energy profiles indicate that the R1 + R2 → P1 process releases a great deal of energy in the solvent acetone in the first reaction (i.e., alkylation), yielding a large amount of P1. In the second reaction (i.e., hydroxyalkylation), in which the solvent is acetonitrile rather than acetone, the Rs1 + Rs2 → Ps1 process is also an exothermic reaction. However, only 10.4 kcal mol⁻¹ energy is released, and the reverse reaction (Ps1 → Rs1 + Rs2) with an energy barrier of 31.5 kcal mol⁻¹ could occur at a temperature of 120 °C. Moreover, Ps1 could undergo a further series of reactions (HAT, C–O bonding, homolysis, HAT) to yield the final product P2. Furthermore, the Ps1 → P2 process releases a much greater amount of energy (66.8 kcal mol⁻¹), and the energy barrier of the reverse reaction is sufficiently high to prevent it from occurring. These factors indicate that product P2 can be yielded in large quantities and can exist in the second reaction. The electron spin density maps provide insight into the single-electron transfer process. All calculations agree with the experimental results. We anticipate that these results will be of great benefit to understand similar reactions between quinoxalin-2(1H)-ones and alkylboronic acids.