A pH-Switchable Electrostatic Catalyst for the Diels-Alder Reaction: Progress Towards Synthetically-Viable Electrostatic Catalysis.

Density functional theory calculations at the SMD/M06-2X/6-31+G(d,p)//M06-2X/6-31G(d) level of theory have been used to computationally design and test a pH-switchable electrostatic organocatalyst for Diels-Alder reactions. The successful cata-lyst design, bis(3-(3-phenylureido)benzyl)ammonium, was studied for the reaction of p-quinone with range of cyclic, hetero-cyclic and acyclc dienes and also the reaction of cyclopentadiene with maleimide and N-phenylmaleimide. All reactions showed significant enhancements in catalysis (10-32 kJ mol-1 in barrier lowering) when the catalyst was protonated, con-sistent with electrostatic stabilization of the transition state. Electrostatic effects were found to diminish in polar solvents but were predicted to remain significant in non-polar solvents.