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One-Pot Sequential Azide–Alkyne [3+2] Cycloaddition and Atom Transfer Radical Addition (ATRA): Expanding the Scope of In Situ Copper(I) Regeneration in the Presence of Environmentally Benign Reducing Agent



One-pot sequential reactions involving azide–alkyne [3+2] cycloaddition and atom transfer radical addition (ATRA) catalyzed by [CuII(TPMA)X][X] {X = Br or Cl, TPMA = tris(2-pyridylmethyl)amine} in the presence of ascorbic acid as a reducing agent are reported. Reactions with azidopropyl methacrylate and 1-(azidomethyl)-4-vinylbenzene in the presence of a variety of alkynes [phenylacetylene, (3,4-difluorophenyl)acetylene, propargyl alcohol, 2-methyl-3-butyn-2-ol, methyl propiolate and ethyl propiolate] and alkyl halides (carbon tetrachloride, carbon tetrabromide, ethyl trichloroacetate, methyl trichloroacetate, ethyl dichloroacetate, methyl dichloroacetate, dichloroacetonitrile and 2-bromopropionitrile) proceeded efficiently to yield highly functionalized (poly)halogenated esters and aryl compounds containing a triazolyl group in the presence of as low as 0.5 mol-% of the catalyst. It is envisioned that the presented methodology could have further implications in the organic synthesis of functionalized triazoles, which have recently been identified as the lead targets for the screening of potential pharmaceutical drugs.