Abstract
Two of the most prominent factors greatly improving the rate and selectivities of Diels-Alder reactions, the aqueous solution and Lewis acids, have been investigated in detail. The stereospecific transition structures of the butadiene and acrolein Diels-Alder reaction in vacuum, with explicit and continuum solvent models, and with Lewis acid catalysts have been studied using the Becke three parameter density functional theory with the 6--31 G(d) basis set. The molecular origins of the solvent and Lewis acid catalysis have been analyzed.The effect of solvent on the activation energies and endo/exo selectivity have been approximated by the polarizable continuum model (PCM), explicit definition of one, two and three waters, and the combined strategy of the discrete-continuum model. The fall aqueous acceleration and enhanced endo/exo selectivity observed by experiment is computed only when solvation forces are approximated by the discrete-continuum model. Two explicit waters are used to satisfy localized hydrogen bonding of acrolein and induce a charge polarization of the endo cis transition structure. Significant bulk phase effects beyond hydrogen bonding and enforced hydrophobic interactions are computed for the first time. The catalytic and endo/exo selectivity results are consistent with the hypothesis of maximum accumulation of unsaturation, and support the importance of antihydrophobic cosolvents in stabilizing hydrophobic regions of transition structures.The effect of Lewis acid catalysis has been analyzed using BF2OCH 3 as the Lewis acid catalyst. A novel combination of two specific intermolecular interactions between the Lewis acid and the transition structure is found to lower the activation energy and amplify endo/exo selectivities. The Lewis acid B-X (X = F, O) bond is computed to have a coplanar conformational preference with the formyl group of acrolein. The interaction between the formyl hydrogen atom and the Lewis acid is referred as nontraditional (O=C-H &cdots; X) hydrogen bonding. Simultaneously, an electrostatic interaction between the Lewis acid and the diene has also been found to be important, where the fluorine substituent interact with the diene proton in the transition structure. To probe the strength of the two interactions, the fluorine substituents on the Lewis acid have been changed to hydrogen one at a time. The newly discovered unusual hydrogen bond interactions has been found to affect both the rate and endo selectivity of the reaction. These results provide further insight into how Lewis acids influence chemical reactions, and should establish opportunities in the design of future catalytic systems.