Nickel-Catalyzed Azide–Alkyne Cycloaddition To Access 1,5-Disubstituted 1,2,3-Triazoles in Air and Water

Abstract

Transition-metal-catalyzed or metal-free azide-alkyne cycloadditions are methods to access 1,4- or 1,5-disubstituted 1,2,3-triazoles. Although the copper-catalyzed cycloaddition to access 1,4-disubstituted products has been applied to biomolecular reaction systems, the azide-alkyne cycloaddition to access the complementary 1,5-regioisomers under aqueous and ambient conditions remains a challenge due to limited substrate scope or moisture-/air-sensitive catalysts. Herein, we report a method to access 1,5-disubstituted 1,2,3-triazoles using a CpNi/Xantphos catalytic system. The reaction proceeds both in water and organic solvents at room temperature. This protocol is simple and scalable with a broad substrate scope including both aliphatic and aromatic substrates. Moreover, triazoles attached with carbohydrates or amino acids are prepared via this cycloaddition.

Recent Developments in Metal‐Catalyzed Bio‐orthogonal Reactions for Biomolecule Tagging

“…A) Generalschemeo f the Huisgen reaction and CuAAC. [28] Initial investigationsi nto the NiAAC were performed by treating benzyl azide and phenylacetylene with a nickel catalysta tr oom temperature withoutadegassing step. C) Synthesis of the 1,5-disubstituted 1,2,3-triazole ring by using ar uthenium catalyst.…”

“…In 2017, Hong et al reported nickel-catalyzed azide-alkyne cycloaddition (NiAAC; Scheme 8D). [28] Initial investigationsi nto the NiAAC were performed by treating benzyl azide and phenylacetylene with a nickel catalysta tr oom temperature withoutadegassing step. Interestingly,i nt he absence of the nickelocene (Cp 2 Ni)o rb identate Xantphos ligand, the reaction for the formation of 1,2,3-triazole was not successful.…”

Alkyl Propiolates Participated [3+2] Annulation for the Switchable Synthesis of 1,5‐ and 1,4‐Disubstituted 1,2,3‐Triazoles Containing Ester Side Chain

“…To develop applicable approaches allowing the selective synthesis of 1,5‐disubstituted 1,2,3‐triazoles, huge endeavors have been devoted. In this regard, the synthesis employing the catalysis of transition metal species such as iridium, ruthenium, nickel have been disclosed. The rare earth samarium has also been found as practical catalyst in catalyzing the synthesis of 1,5‐disubstituted 1,2,3‐triazoles .…”

Iridium‐Catalyzed Hydroxyl‐Enabled Cycloaddition of Azides and Alkynes

“…Thus the ideal CuAAC is considered as click reaction and widely used in organic chemistry, medicinal chemistry, material chemistry and chemical biology. [5] For internal alkynes, Fokin found that the CuAAC is applicable for 1-iodoalkynes, and Micouin revealed that aluminum acetylide is also compatible in this process (Scheme 1C). [4] Recently, Hong and coworkers established a similar reaction using Cp 2 Ni/Xantphos as catalyst, and this process is compatible with water and air.…”

“…[4] Recently, Hong and coworkers established a similar reaction using Cp 2 Ni/Xantphos as catalyst, and this process is compatible with water and air. [5] For internal alkynes, Fokin found that the CuAAC is applicable for 1-iodoalkynes, and Micouin revealed that aluminum acetylide is also compatible in this process (Scheme 1C). [6,7] In 2014, Jia and Sun developed an iridium-catalyzed regioselective cycloaddition of azides and internal thioalkynes.…”