The mechanism of the phosphine-catalyzed oxa-Michael reaction: a DFT investigation

Two possible model reaction mechanisms of trimethylphosphine-catalyzed oxa-Michael addition of phenol and methanol to acrolein, one in which trimethylphosphine acts as a nuclephile and adds to acrolein to generate the enolate anion (mechanism 1) and the other in which trimethylphosphine acts as a base and reacts with the hydroxyl compound to generate PhO⁻ /MeO⁻ anion (mechanism 2), were computed in the gas phase using the B3LYP functional and the ωB97XD functional which incorporates dispersion correction, with the same basis set, 6–31 + G(d). In mechanism 1, the third step involving the attack of PhO⁻ or MeO⁻ on the intermediate, Int.2 accompanied by the loss of Me₃P occurring through TS3 is the rate-determining step. In this case, however, the activation free energy for the attack of PhO⁻ is found to be smaller than for MeO⁻, which is contrary to the experimental results wherein methanol is reported to react faster than phenol. In mechanism 2, the second step involving nucleophilic attack of the PhO⁻ or MeO⁻ anion on C3 of acrolein via TS2’ is the rate-differentiating step vis-à-vis the reactions of phenol and methanol with acrolein. In this case, the activation free energy barrier for PhO⁻ is much higher than for MeO⁻; in fact, the reaction with latter is found to be barrierless. It is in perfect compliance with the experimental results. These results indicate that trimethylphosphine-catalyzed oxa-Michael addition of phenol and methanol with acrolein occurs via the mechanism in which phosphine acts as a base. Acetonitrile is found to lower the activation energies.