A Combined Microwave/Continuous Flow Approach for the Iodination of Anilines and Consecutive Mizoroki-Heck Cross-Coupling

Abstract

Within this work, we report a modular, microwave-assisted continuous-flow approach for the selective iodination of unprotected anilines, achieving control of regioselectivity, over-halogenation, and the need for a protecting group. Microwaves (MW) irradiation enables rapid and localised energy transfer to accelerate kinetics and suppress by-product formation, while the use of a recoverable reaction medium as acetonitrile-water azeotrope (MeCN/H2Oaz) led to substantial improvements in both reaction mass efficiency (RME) and E-factor. Moreover, it has been demonstrated that the protocol can be telescoped by combining MW/Flow iodination and the representative Mizoroki-Heck reaction in continuous flow.The protocol eliminates the need for intermediate isolation and solvent switching. This integrated process delivers functionalized products rapidly, with high selectivity and reduced waste compared to conventional protocols.