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.