Direct C4 Halogenation of Isoquinolines via a Boc2O-Mediated Dearomatization Strategy

J Org Chem. 2025 Jun 27;90(25):8570-8577. doi: 10.1021/acs.joc.5c00535. Epub 2025 Jun 15.

Abstract

A cost-effective method for directly halogenating isoquinolines at the C4 position has been developed through a one-pot sequence involving Boc2O-mediated dearomatization, electrophilic halogenation (X = Cl, Br, I), and acid-promoted rearomatization. This reaction exhibited high C4 site selectivity, efficiently affording 4-halogenated isoquinolines, and demonstrated good functional group tolerance at C5-C8. In addition, the C-X bond-containing products could serve as versatile synthetic intermediates for further modification of isoquinolines, including Suzuki coupling, Sonogashira coupling, and Stille coupling.