Iodination of Arenes Driven by Hypervalent Iodine-Based Halogen Bonding: Compatible with Electron-Deficient Arenes

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Medicinal Chemistry

Background:

• Iodoarenes are vital synthetic building blocks for pharmaceuticals, agrochemicals, and materials.
• Efficient synthesis of iodoarenes is crucial for various chemical industries.
• Developing new methods for iodoarene synthesis is an ongoing research area.

Purpose of the Study:

• To develop a mild and efficient method for electrophilic iodination of arenes.
• To introduce a novel reagent system for the synthesis of iodoarenes.
• To demonstrate the utility of the new method in late-stage functionalization of complex molecules.

Main Methods:

• Utilized a two-coordinate hypervalent iodine reagent, (phenyliodonio)sulfamate (PISA), in combination with molecular iodine (I2).
• Optimized reaction conditions by modulating solvent and reagent stoichiometry.
• Employed Density Functional Theory (DFT) calculations to elucidate the reaction mechanism.

Main Results:

• Achieved mild electrophilic iodination of arenes with diverse electronic properties.
• Demonstrated excellent functional group compatibility, enabling late-stage iodination of pharmaceuticals and natural products.
• DFT calculations revealed PISA's role as a halogen bond donor, facilitating I-I bond cleavage and stabilizing intermediates.

Conclusions:

• The PISA/I2 system provides a unique and effective approach for electrophilic iodination.
• This method offers a valuable tool for the synthesis of complex iodoarene-containing molecules.
• The study highlights the importance of hypervalent iodine reagents and halogen bonding in synthetic chemistry.