Halogen bond catalysis: In silico design

15 Dec 2015 NUS computational chemists designed halogen bonding based organocatalysts for important organic reactions.

Halogen bond, a non-covalent interaction involving a halogen atom as an acceptor of electron density, has emerged in recent years as an important element of molecular recognition and has numerous applications such as molecular self-assembly of functional materials and protein-drug interaction (see Figure). Due to its bond strength and directionality, halogen bonding has great potential to become a complementary molecular tool to hydrogen bonding in rational catalyst design.

Using density functional calculations, a team led by Prof WONG Ming Wah Richard from the Department of Chemistry in NUS has shown the use of halogen-bond donors as non-covalent activators in Lewis acid catalysis. In particular, they have proposed a new type of triaryl benzene organocatalysts via multiple halogen bond donors (e.g. perfluoro-iodophenyl  group). This “in silico” designed halogen bonding (XB) based catalyst was applied to several important types of organic reaction, namely Diels-Alder reaction, Claisen rearrangement and cope-type hydroamination. The calculated catalytic mechanisms and activation barriers of these reactions readily demonstrate that the designed system is a promising Lewis acid catalyst via halogen bond mode of activation.

Figure shows (1) halogen bond interaction halobenzene and formaldehyde, (2) multiple halogen bonds between the “in silico” designed catalyst and a carbonyl group, and (3) halogen bond catalysis applied to Diels-Alder reaction.

Reference

Kee CW, Wong MW, “In Silico Design of Halogen Bond Based Catalyst for Diels-Alder Reaction, Claisen Rearrangement and Cope-Type Hydroamination”, ACS Catalysis, submitted.