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.

WONG Richard Dec

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.



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.