Work

Organophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C–H Bonds via H/D Exchange with D2O

Year: 2024

Type: article

Abstract: 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 D 2 O. 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-stage modification of complex amine-containing pharmaceuticals allows for the development of a viable method for efficient α-deuteration of the important functionality.

Source: Organic Letters

DOI: 10.1021/acs.orglett.4c03493

Authors: Xiang Meng, Chao Che, Yue Dong, Qiangqiang Liu, Wei Wang

Institution: University of Arizona

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: G4960367858, G5156933358