Computational exploration of a redox neutral organocatalytic Mitsunobu reaction.
The mechanism of the redox neutral organocatalytic Mitsunobu reac tion, catalyzed by (2 hydroxybenzyl)diphenylphosphine oxide, re ported by Denton et al. has been studied computationally with oB97X D density functional theory. We discovered that the nucleo philic substitution reaction between carboxylate and alkoxyphospho nium ions, to reform the phosphine oxide catalyst, is the rate determining step of the overall process and is significantly accelerated compared with a general acid catalyzed SN2 reaction. The (2 hydroxybenzyl)diphenylphosphine oxide is regenerated and activated in every catalytic cycle via intramolecular dehydration/cyclization. We also designed several phosphine oxide catalysts that we predict to be more effective catalysts.
Journal of the American Chemical Society