Synthesis of Benzoxazoles Using Electrochemically Generated Hypervalent Iodine

Area of Science:

• Organic Electrochemistry
• Synthetic Organic Chemistry
• Medicinal Chemistry

Background:

• Electrochemical synthesis offers a sustainable alternative to traditional organic synthesis.
• Developing efficient and reusable mediators is crucial for practical electrochemical applications.
• Benzoxazoles are important heterocyclic compounds with diverse biological activities.

Purpose of the Study:

• To report an indirect ("ex-cell") electrochemical synthesis of benzoxazoles.
• To utilize a novel iodine(I)/iodine(III) redox mediator system for this transformation.
• To investigate the mechanism of benzoxazole formation and the compatibility with functional groups.

Main Methods:

• Indirect electrochemical synthesis using an "ex-cell" setup.
• Employing a tethered iodophenyl-tetra-alkylammonium salt as a redox mediator.
• Performing anodic oxidation without supporting electrolyte.
• Utilizing control experiments and Density Functional Theory (DFT) calculations for mechanistic studies.

Main Results:

• Successful synthesis of benzoxazoles from imines via an electrochemical route.
• Demonstration of a reusable iodine-based redox mediator, eliminating the need for supporting electrolytes.
• The method exhibits compatibility with various redox-sensitive functional groups.
• Proposal of a novel concerted reductive elimination mechanism for benzoxazole formation.

Conclusions:

• The developed "ex-cell" electrochemical method provides an efficient and sustainable pathway for benzoxazole synthesis.
• The reusable iodine mediator and electrolyte-free conditions highlight the practical applicability of this approach.
• The proposed mechanism offers new insights into heterocyclic compound formation via electrochemistry.