Synlett 2021; 32(12): 1241-1245
Synthesis of α-Deuterioalcohols by Single-Electron Umpolung Reductive Deuteration of Carbonyls Using D2 O 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
,
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 D2 O 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 D2 O is greener and more efficient compared to traditional pyrophoric-metal-deuteride-mediated reductive deuterations.
Key words
reductive deuteration -
ketones -
aldehydes -
α-deuterioalcohols -
deuterating chiral centers -
D
2 O
Supporting Information
Supporting information for this article is available online at https://doi.org/10.1055/a-1523-3336.
Supporting Information
Publication History
Received: 09 May 2021
© 2021. Thieme. All rights reserved
Georg Thieme Verlag KG
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