Hetero-Diels-Alder reactions continue to be a key reaction for organic chemists. In order to improve the rates, three are the traditional approaches: 1) Danishefsky's diene has been used to increase reactivity towards very non-reactive dienophiles; 2) Lewis acids, like boron trifluoride, have been extensively employed; and 3) synthetic pockets can be used to accelerate these reactions through non-covalent interactions. Baba and coworkers (Angew. Chem. Int. Ed., 2012, 51, 3867) recently reported the synthesis of the cage-shaped borate 2, which combines the reactivity of a Lewis acid and the structural features of clathrates. In addition, the aromatic-lined cavity of 2 allows selective discrimination between aliphatic and aromatic aldehydes through molecular recognition. Here, we quantify the contribution of the non-covalent interactions to the molecular recognition process of catalysts 2 towards aromatic aldehydes. B97D/TZV(2d,2p) computations indicate that the pre-reactive complex is stabilized to a greater extent if the cavity is built with bigger aromatic moieties. These results suggest p-stacking interactions are operative in determining the aromatic selectivity of this catalyst. 

Origin of aromatic recognition in a Lewis acid catalyzed hetero-Diels-Alder reaction

245th National Meeting (2013)

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