Trifluoromethanesulfonyl azide as a bifunctional reagent for metal-free azidotrifluoromethylation of unactivated alkenes |
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Authors: | Hong-Gui Huang Weishuang Li Dayou Zhong Hu-Chong Wang Jing Zhao Wen-Bo Liu |
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Institution: | Sauvage Center for Molecular Sciences, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), College of Chemistry and Molecular Sciences, Wuhan University, 299 Bayi Road, Wuhan 430072 Hubei China, |
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Abstract: | 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 (N3SO2CF3). This unprecedented two-component reaction employs readily available N3SO2CF3 as a bifunctional reagent to concurrently incorporate both CF3 and N3 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 CF3-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 (N3SO2CF3) as a bifunctional reagent for both CF3 and N3 groups. |
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