Cu -catalyzed azide-alkyne cycloaddition

M. Meldal and C. W. Tomqe, Cu-catalyzed azide-alkyne cycloaddition, Chem. Rev., 108 (2008) 2952-3015. 

Apart from the utilization of aryl- and vinyl-diazoacetates that can achieve the moderate to high chemo-, regio-, and enantioselectivity in intermolecular asymmetric C—H bond insertion reactions, Af-sulfonyl-l,2,3-triazole 11 was found to be able to function as an alternative carbene precursor for diverse transformations (Scheme 1.4). One advantage for using the N-sulfonyl-1,2,3-triazole is that it could be easily prepared by the Cu -catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and in some cases, delicately designed reactions can be conducted in a one-pot procedure starting from alkynes and sulfonyl azides. Moreover, since there exists an inherent equilibrium... 

Recent studies on the reaction mechanism provided the experimental evidence for a dinuclear Cu intermediate complex involved within the reaction steps [28]. Although the Huisgen s original reaction mechanism is considered to be concerted, where the old bonds break at the same time as the new bonds form, the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) is a stepwise process. Ever since the initial report, this reaction has found extensive applications in biotechnology [29-31], material sciences [32-34] and drug discovery [35, 36]. 

Presolski SI, Hong V, Cho S-H, Finn MG (2010) Tailored ligand acceleration of the cu-catalyzed azide-alkyne cycloaddition reaction practical and mechanistic implications. J Am Chem Soc 132 14570-14576... 

Rodionov VO, Presoldd SI, Dfaz Diaz D, Fokin VV, Finn MG (2007) Ligand-accelerated Cu-catalyzed azide-alkyne cycloaddition a mechanistic repOTt J Am Chem Soc 129 12705-12712... 

CuAAC Cu-catalyzed azide-alkyne cycloaddition DA Diels-Alder... 

The introduction of functional groups on canonical nucleobases can be restrained, because these modified nucleobases need to be compatible with the enzymatic steps required in the SELEX process. A novel approach termed click-SELEX uses a modular strategy based on Cu -catalyzed azide-alkyne cycloaddition to generate modified nucleic acid libraries (Fig. 5) [175]. 

Binder and Kluger [41, 42] utilized the Hamilton wedge and THY as molecular recognition handles in the construction of side-chain-functionalized poly(oxanorbornene dicarboximides) using a ROMP/click methodology. Monomers functionalized with azido or alkynyl side chains were polymerized to either homopolymers or block copolymers and subsequently subjected to Cu-catalyzed azide-alkyne cycloaddition [72] to install the desired H-bonding motifs. 

The Huisgen azide-alkyne 1,3-dipolar cycloaddition (AAC) [75] and later developed Cu-catalyzed azide-alkyne cycloadditions (CuAAC) [76-80], which are the most commonly utilized methods for the synthesis of N-substituted 1,2,3-triazoles, will not covered here. Very recently, Bi and co-workers [81] developed an elegant silver-catalyzed tandem hydroazidation/alkyne-azide cycloaddition of diynes with TMSN3 providing an easy access to 1,5-fused 1,2,3-triazole frameworks [82, 83]. 

Meldal M, Tompe CW (2008) Cu-catalyzed azide — alkyne cycloaddition. Chem Rev 108 2952-3015... 

Applications of the Cu-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) in Peptides... 

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