Titanium-catalyzed radical-type deuteriodeboronation of arylboronates

Abstract

Deuterated aromatic compounds have extensive applications in organic synthesis and the pharmaceutical industry. Nevertheless, the development of cost-effective transition metal catalysis remains pressing. In this study, we present an unprecedented titanium-catalyzed deuteriodeboronation of arylboronates, which enables the efficient synthesis of deuterated aromatic rings with excellent functional group compatibility and high yields. Mechanistic studies have shown that arylboronates undergo base-mediated transmetallation with titanium(IV) to produce key aryl titanium intermediates, which undergo homolytic cleavage to release aryl radicals and Ti(III) species, followed by deuterium atom abstraction from CD₃CN resulting in deuterated aromatics. Controlled experiments as well as HRMS provide evidence for the presence of these species. In particular, the gram-scale synthesis experiment and the preparation of the antidepressant drug deuterated N-methyl duloxetine showed its potential application. This methodology establishes a more environmentally friendly approach for deuteriodeboronation and provides a novel pathway for the development of deuterated compounds.