Density functional study of noncovalent catalysis of the Diels-Alder reaction by the neutral hydrogen bond donors thiourea and urea

The Diels-Alder reaction between cyclopentadiene and methyl vinyl ketone has been investigated by density functional calculations at the B3LYP/6-31+G* level, both in the absence and presence of the hydrogen-bonding catalysts thiourea and urea. The computed transition structures are concerted, but highly asynchronous in all cases. The addition of thiourea or urea accelerates the reaction and slightly changes the endo/exo selectivity. The activation barriers are lowered by 2-3 kcal/mol, while the activation free energies show smaller reductions due to unfavorable entropic effects. The addition of BF3 causes a more pronounced decrease in the computed barriers by 8-11 kcal/mol. Despite their lower efficiency, hydrogen-bonding catalysts such as thiourea and urea may still offer an attractive alternative to Lewis acids because they do not suffer from product inhibition and can be used in aqueous solution.