Photocatalyzed Reductive Amination for Multiple Deuteration of Amines

The practical utility of deuterated amines as absorption, distribution, metabolism, excretion (ADME) internal standards, or drug candidates requires significant mass differentiation from nondeuterated analogs. Traditional methods for synthesizing poly deuterated pharmaceutical amines rely on multistep syntheses with costly deuterated precursors (aldehydes/amines). Here, we present a synergistic photocatalytic system integrating CO2•–-driven deuterated reductive amination (D-RA) with thiol-mediated hydrogen–deuterium exchange (HDE). This tandem system enables α-/β-amino C–H deuteration via inexpensive D2O utilization as both the reductant and deuteration source, achieving efficient mass-differentiated amine synthesis. Furthermore, through thermo-photo relay catalysis, the substrate of this photocatalyzed reductive amination scope extends to inert amides and esters with practical relevance.