DFT Studies on Double Hydrogen Bond Catalysis of Reactions of Distinct Polarity

The Diels–Alder cycloaddition and the enamine‐aldol reactions catalyzed by double‐site hydrogen‐bond donors were computationally studied at the B3LYP and MP2/6‐311++G** levels. The comparison of bifurcated and cooperative H‐bonding activation of the electrophile in both reactions with 1,3‐propanediol, 1,4‐butanediol, glycolic acid and two molecules of methanol strongly suggests that the activation mode depends on the electronic features of the carbonyl oxygen atom in the H‐bond acceptor. The bifurcated arrangement of the hydrogen‐bond donors is predicted to be favoured as the polarity of the reaction increases. Consequently, the transition states of the Diels–Alder reaction are better stabilized by a cooperative interaction with the diols and those of the more polar enamine‐aldol reaction by a bifurcated interaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)