Highly Chemoselective Synthesis of α, α‑Dideuterio Amines by the Reductive Deuteration of Thioamides Using Mild SmI2–D2O

An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI2 and D2O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from...

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Veröffentlicht in:	Organic letters 2024-10, Vol.26 (42), p.9120-9125
Hauptverfasser:	Li, Hengzhao, Wang, Kemeng, Zhao, Wangyu, Li, Xinxin, Fu, Yijing, Do, Hainam, An, Jie, Hu, Zhaonong
Format:	Artikel
Sprache:	eng
Schlagworte:	alcohols chemoselectivity deuterium heterocyclic nitrogen compounds ligands thioamides
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container_issue	42
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container_title	Organic letters
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creator	Li, Hengzhao Wang, Kemeng Zhao, Wangyu Li, Xinxin Fu, Yijing Do, Hainam An, Jie Hu, Zhaonong
description	An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI2 and D2O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like Et3N to improve the reducing power of SmI2, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups. This protocol tolerates both primary and secondary aliphatic and aromatic thioamides, leading to the synthesis of 27 α,α-dideuterio amines and valuable deuterated nitrogen heterocycles with >95% deuterium incorporations.
doi_str_mv	10.1021/acs.orglett.4c03434
format	Article
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Lett</addtitle><date>2024-10-25</date><risdate>2024</risdate><volume>26</volume><issue>42</issue><spage>9120</spage><epage>9125</epage><pages>9120-9125</pages><issn>1523-7060</issn><issn>1523-7052</issn><eissn>1523-7052</eissn><abstract>An efficient and chemoselective protocol for the single-electron-transfer (SET) reductive deuteration of thioamides using SmI2 and D2O is reported. This method uniquely produces α,α-dideuterio amines via a thio-ketyl radical intermediate without generating alcohol byproducts, distinguishing it from the SET reduction of amides. The inherent high reactivity of thioamides obviates the need for ligands like Et3N to improve the reducing power of SmI2, thereby enabling milder reaction conditions that are compatible with a broad range of sensitive functional groups. 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source	ACS Publications
subjects	alcohols chemoselectivity deuterium heterocyclic nitrogen compounds ligands thioamides
title	Highly Chemoselective Synthesis of α, α‑Dideuterio Amines by the Reductive Deuteration of Thioamides Using Mild SmI2–D2O
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