title: Structural Determinants of Alkyne Reactivity in Copper-Catalyzed Azide-Alkyne Cycloadditions.
abstract: This work represents our initial effort in identifying azide/alkyne pairs for optimal reactivity in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions. In previous works, we have identified chelating azides, in particular 2-picolyl azide, as "privileged" azide substrates with high CuAAC reactivity. In the current work, two types of alkynes are shown to undergo rapid CuAAC reactions under both copper(II)- (via an induction period) and copper(I)-catalyzed conditions. The first type of the alkynes bears relatively acidic ethynyl C-H bonds, while the second type contains anN-(triazolylmethyl)propargylic moiety that produces a self-accelerating effect. The rankings of reactivity under both copper(II)- and copper(I)-catalyzed conditions are provided. The observations on how other reaction parameters such as accelerating ligand, reducing agent, or identity of azide alter the relative reactivity of alkynes are described and, to the best of our ability, explained.
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306-4390, USA. xizhang@chem.fsu.edu.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306-4390, USA. peiyeliu@chem.fsu.edu.
authors.forename: Peiye
authors.initials: P
authors.lastname: Liu
authors.affiliation: Department of Chemistry and Biochemistry, Florida State University, 95 Chieftan Way, Tallahassee, FL 32306-4390, USA. lzhu@chem.fsu.edu.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001386:Azides / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008956:Models, Chemical
chemical_list: D000480:Alkynes; D001386:Azides; D003300:Copper
keywords: CuAAC; alkyne; click chemistry; copper; reactivity