Synlett 2021; 32(12): 1241-1245
DOI: 10.1055/a-1523-3336
letter

Synthesis of α-Deuterioalcohols by Single-Electron Umpolung Reductive Deuteration of Carbonyls Using D2O as Deuterium Source

a   Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China
,
Yuxia Hou
a   Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China
,
Zemin Lai
a   Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China
,
Lei Ning
a   Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China
,
Ailing Li
a   Department of Chemistry and Innovation Center of Pesticide Research, China Agricultural University, Beijing 100193, P. R. of China
,
Yixuan Li
b   Department of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China
,
Jie An
b   Department of Nutrition and Health, China Agricultural University, Beijing 100193, P. R. of China
› Author Affiliations
We thank National Key R&D Plan (Grant Number 2017YFD0201900), the National Natural Science Foundation of China (NSFC, Grant Number 21602248) and the Natural Science Foundation of Beijing Municipality (Grant Number 2192026) for financial support.


Abstract

Deuterium incorporation can effectively stabilize the chiral centers of drug and agrochemical candidates that hampered by rapid in vivo racemization. In this work, the synthetically challenging chiral-center deuteration of alcohols has been achieved via a single-electron umpolung reductive-deuteration protocol using benign D2O as deuterium source and mild SmI2 as electron donor. The broad scope and excellent functional group tolerance of this method has been showcased by the synthesis of 43 respective α-deuterioalcohols in high yields and ≥98% deuterium incorporations. The potential application of this versatile method has been exemplified in the synthesis of 6 deuterated drug derivatives, 1 deuterated human hormone, and 3 deuterated natural products. This method using D2O is greener and more efficient compared to traditional pyrophoric-metal-deuteride-mediated reductive deuterations.

Supporting Information



Publication History

Received: 09 May 2021

Accepted after revision: 05 June 2021

Accepted Manuscript online:
05 June 2021

Article published online:
23 June 2021

© 2021. Thieme. All rights reserved

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