A DFT study on the base-catalyzed allylic rearrangement reaction of enol phosphate

Enol phosphates are important intermediates for synthesizing bioactive molecules with neighboring C[double bond, length as m-dash]C and C[double bond, length as m-dash]O motifs, and their synthesis via the Perkow reaction is a highly attractive approach. The allyl rearrangement process involved in the Perkow reaction plays a key role in regulating the Z/E configuration of enol phosphate products. Herein, the mechanism of the base-catalyzed allylic rearrangement reaction of enol phosphates was investigated using density functional theory (DFT) methods. The calculated results of the NEt₃-catalyzed rearrangement reaction show that it undergoes two proton transfer steps and that the rate-determining step is the first proton transfer step with a free energy barrier of 20.7 kcal mol^-1. The modulation effect of different organic base catalysts (NEt₃, Py, (i-Pr)₂NEt, TBD, DBU, and MTBD) on this rearrangement is also discussed. It is found that it is difficult for weak bases such as pyridine to accept a proton from the substrate in the first proton transfer step and that strong bases such as t-BuOK do not perform well in the second proton transfer step. 1,8-Diazabicyclo[5.4.0]undecane-7-ene (DBU) is proposed as the optimum base to catalyze the allylic rearrangement reaction of enol phosphates, with a calculated energy barrier of 19.1 kcal mol^-1 for the first proton transfer step. This study provides valuable guidance for screening efficient base catalysts for the synthesis of enol phosphates, and the approach could be applied to other base-catalyzed organic reactions.