Organophotocatalytic Selective Deuteration of Metabolically Labile Heteroatom Adjacent C-H Bonds Via H/D Exchange with DO

Overview

Journal Org Lett

Publisher American Chemical Society

Specialties Biochemistry
Chemistry

Date 2024 Oct 7

PMID 39374416

Authors

Xiang Meng

Chao Che

Yue Dong

Qiangqiang Liu

Wei Wang

Affiliations

Soon will be listed here.

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 DO. 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.

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