In Silico Design of Halogen-Bonding-Based Organocatalyst for Diels–Alder Reaction, Claisen Rearrangement, and Cope-Type Hydroamination

Using DFT calculations, we investigated the use of halogen bonding (XB) interactions to accelerate and control organic reactions, namely Diels–Alder reaction, Claisen rearrangement, and Cope-type hydroamination. Our designed triarylbenzene tripodal organocatalyst is characterized by three halogen bond donors, perfluoro-iodophenyl groups. The calculated transition states unravel multiple halogen bonds between the iodine atoms and various types of halogen bond acceptors (lone pair, π and σ bonds). These cooperative noncovalent interactions provide efficient binding between the catalyst and substrate (∼15 kcal/mol binding energy) and are the key factors for transition-state stabilization and molecular recognition. On the basis of our DFT calculations and calculated turnover frequencies, the XB-catalyzed reactions are found to be competitive with the corresponding hydrogen bonding catalysis reported in literature.