biostudies-literatureMeng XCollege of Pharmacy, University of ArizonaNational Institute of General Medical SciencesNIGMS NIH HHS8961-8966https://www.ebi.ac.uk/biostudies/studies/S-EPMC11527481biostudies-literatureUnknown26(41)We report a general approach for efficient deuteration of the metabolically labile α-C-H bonds of widespread amides and amines. Temporarily masking the secondary amine group as a carbamate allows an unprecedented photoredox hydrogen atom transfer-promoted α-carbamyl radical formation for efficient H/D exchange with D₂O. The mild protocol delivers structurally diverse α-deuterated secondary amines including "privileged" piperidine and piperazine structures highly regioselectively with excellent levels of deuterium incorporation (≤100%). Furthermore, we successfully implemented the strategy for α-deuteration of amides, lactams, and ureas with high regioselectivity and high levels of D incorporation. Finally, the observed efficient deuteration of secondary alcohol moieties in late-Organic lettersOrganophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C-H Bonds via H/D Exchange with D<sub>2</sub>O.PMC115274815R01GM125920R01 GM125920Che CDong YLiu QWang WMeng XfalseOrganophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C-H Bonds via H/D Exchange with D<sub>2</sub>O.We report a general approach for efficient deuteration of the metabolically labile α-C-H bonds of widespread amides and amines. Temporarily masking the secondary amine group as a carbamate allows an unprecedented photoredox hydrogen atom transfer-promoted α-carbamyl radical formation for efficient H/D exchange with D₂O. The mild protocol delivers structurally diverse α-deuterated secondary amines including "privileged" piperidine and piperazine structures highly regioselectively with excellent levels of deuterium incorporation (≤100%). Furthermore, we successfully implemented the strategy for α-deuteration of amides, lactams, and ureas with high regioselectivity and high levels of D incorporation. Finally, the observed efficient deuteration of secondary alcohol moieties in late-2024-01-01T00:00:00Z2024 Oct2025-04-19T09:56:59.226Z2025-04-19T09:56:59.226ZS-EPMC115274813937441610.1021/acs.orglett.4c03493