Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes

Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks fr...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2021-03, Vol.12 (9), p.321-3215
Main Authors: Huang, Hong-Gui, Li, Weishuang, Zhong, Dayou, Wang, Hu-Chong, Zhao, Jing, Liu, Wen-Bo
Format: Article
Language:English
Subjects:
Alkenes
Amino acids
Azides (organic)
Chemical reactions
Chemistry
Functional groups
Natural products
Reagents
Transition metals
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Summary:Vicinal trifluoromethyl azides have widespread applications in organic synthesis and drug development. However, their preparation is generally limited to transition-metal-catalyzed three-component reactions. We report here a simple and metal-free method that rapidly provides these building blocks from abundant alkenes and trifluoromethanesulfonyl azide (N 3 SO 2 CF 3 ). This unprecedented two-component reaction employs readily available N 3 SO 2 CF 3 as a bifunctional reagent to concurrently incorporate both CF 3 and N 3 groups, which avoids the use of their expensive and low atom economic precursors. A wide range of functional groups, including bio-relevant heterocycles and amino acids, were tolerated. Application of this method was further demonstrated by scale-up synthesis (5 mmol), product derivatization to CF 3 -containing medicinal chemistry motifs, as well as late-stage modification of natural product and drug derivatives. A two-component and metal-free azidotrifluoromethylation of alkenes is realized using readily synthesized trifluoromethanesulfonyl azide (N 3 SO 2 CF 3 ) as a bifunctional reagent for both CF 3 and N 3 groups.
ISSN:2041-6520
2041-6539
DOI:10.1039/d0sc06473d