Azide–Alkyne “Click” Reaction in Water Using Parts-Per-Million Amine-Functionalized Azoaromatic Cu(I) Complex as Catalyst: Effect of the Amine Side Arm

Abstract

A series of Cu(II) complexes, 1−4 and 6, were synthesized through a reaction of amine-functionalized pincer-like ligands, HL 1,2 , L a,b , and a bidentate ligand L 1 with CuCl 2 •2H 2 O. The chemical reduction of complex 1 using 1 equiv of sodium Lascorbate resulted in a dimeric Cu(I) complex 5 in excellent yield. All of the complexes, 1−6, were thoroughly characterized using various physicochemical characterization techniques, single-crystal X-ray structure determination, and density functional theory calculations. Ligands HL 1,2 and L a,b behaved as tridentated donors by the coordination of the amine side arm in their respective Cu(II) complexes, and the amine side arm remained as a pendant in Cu(I) complexes. All of these complexes (1−6) were explored for copper(I)-catalyzed 1,3-dipolar azide−alkyne cycloaddition (CuAAC) reaction at room temperature in water under air. Complex 5 directly served as an active catalyst; however, complexes 1−4 and 6 required 1 equiv of sodium L-ascorbate to generate their corresponding active Cu(I) catalyst. It has been observed that azobased ligand-containing Cu(I)-complexes are air-stable and were highly efficient for the CuAAC reaction. The amine side arm in the ligand backbone has a dramatic role in accelerating the reaction rate. Mechanistic investigations showed that the alkyne C−H deprotonation was the rate-limiting step and the pendant amine side arm intramolecularly served as a base for Cu-coordinated alkyne deprotonation, leading to the azide−alkyne 2 + 3 cycloaddition reaction. Thus, variation of the amine side arm in complexes 1−4 and use of the most basic diisopropyl amine moiety in complex 4 has resulted in an unique amine-functionalized azoaromatic Cu(I) system for CuAAC reaction upon sodium L-ascorbate reduction. The complex 4 has shown excellent catalysis at its low partsper-million level loading in water. The catalytic protocol was versatile and exhibited very good functional group tolerance. It was also employed efficiently to synthesize a number of useful functional triazoles having medicinal, catalytic, and targeting properties.

N‐heterocyclic Thiols based Copper Complexes: Syntheses, Structure and Catalytic Studies for Azide‐Alkyne Cycloaddition Reaction

“…In this reaction, Cu(I) served as an active species, capable of generating from Cu(II) by applying a reducing agent such as sodium ascorbate. [30] The Cu(II) moiety can also be reduced without using a reducing agent, either by alkyne homocoupling or solvent oxidation. [31] However, the use of in-situ generated organic azides in the Click reaction is a good choice and reduces the detonation nature of organic azides.…”

“…Recent Nobel Prizes in Click Chemistry have triggered this field in the science domain. In this reaction, Cu(I) served as an active species, capable of generating from Cu(II) by applying a reducing agent such as sodium ascorbate [30] . The Cu(II) moiety can also be reduced without using a reducing agent, either by alkyne homocoupling or solvent oxidation [31] .…”

Alcohol Dehydrogenation-Triggered Selective C3-Alkylation of Indoles by Homogeneous Azo-aromatic Cobalt Catalysts

“…Taking advantage of redox non-innocent behavior of the azo-aromatic compound, − we designed and synthesized the pincer-like azo-aromatic ligands ( L 1 – 3 , Scheme ) as well as their cobalt­(II) complexes ( 1 – 3 ) (Scheme ). Azo aromatics are known to exist in one-electron reduced azo-anion radicals and two-electron reduced hydrazido forms. ,,, It is also reported that the azo moiety of the ligand can abstract a hydrogen atom efficiently from coordinated deprotonated alcohol, leading to dehydrogenative formation of carbonyl compounds. − Complexes 1–3 have shown facile L/L • and Co­(II)/Co­(I) reductions in a close-lying redox potential, which might be beneficial for chemical transformations that occur through two electron oxidations.…”

Copper(II) Complexes Supported by Bis(imino)pyridine Ligands: Synthesis and Catalysis on Azide‐Alkyne Click Reactions

“…Transition metal complexes supported by pincer ligands have been used as catalysts in azide‐alkyne Click reactions [12] . Samanta and co‐workers synthesized a series of pincer type of copper(II) complexes having new strong π‐acceptor type azo‐aromatic ligands and utilized as catalysts for azide‐alkyne cycloaddition reactions [11c] . Our group reported a series of copper(II) complexes supported by arylselenolate‐based ligands for azide‐alkyne cycloaddition in water [13] .…”