Indium-Catalyzed Highly Efficient Three-Component Coupling of Aldehyde, Alkyne, and Amine via C−H Bond Activation

Abstract

In this paper, indium(III) chloride was found to be a highly effective catalyst for the three-component coupling reactions of aldehydes, alkynes, and amines (A(3)-coupling) via C-H activation. The reactions could be applied to both aromatic and aliphatic aldehydes and alkynes. Nearly quantitative yields of the desired products were obtained in most cases. No cocatalyst or activator is required, and water is the only byproduct in the reactions. Furthermore, a tentative mechanism of the InCl(3)-catalyzed one-pot, three-component coupling of aldehyde, alkyne, and amine is proposed.

Efficient Microwave‐Assisted Synthesis of Secondary Alkylpropargylamines by Using A3‐Coupling with Primary Aliphatic Amines

“…Several transition-metal catalysts have been exploited that activate the CÀH bond of the terminal alkyne. Ag I salts, [5] Au I /Au III salts, [6] Au III -salen (salen = N,N'-bis(salicylidene)ethylenediamine) complexes, [7] Cu I salts, [8] Ir I complexes, [9] Hg 2 Cl 2 , [10] Cu/Ru II bimetallic systems, [11] InCl 3 , [12] ZnCl 2 , [13] FeCl 3 [14] and nano CuO compounds [15] have all been used to run this reaction under homogeneous conditions. Moreover, Au I , Ag I and Cu I in ionic liquids and supported Au III , Ag I , Cu I and CuCl were successfully used to catalyse A 3 -coupling reactions under heterogeneous conditions with preservation of the transition-metal catalyst.…”

“…As stated in the literature, the initial reagent ratio was selected as 1.3 equivalents of amine, 1.0 equivalent of aldehyde and 1.6 equivalents of alkyne [8c] with toluene as the solvent. [12,14] Reactions were carried out in the presence of different copper salts under microwave irradiation at various ceiling temperatures (Table 1). Relatively low concentrations of the CuI catalyst resulted in low yields of the propargylamine 4{1} (Table 1, entries 1-5).…”

“…The application of InCl 3 did not yield any trace of the product (Table 1, entry 21). [12] Finally, we tried the recently reported catalyst FeCl 3 , which is described as being very efficient in reactions involving secondary amines. [14] Unfortunately, this catalyst did not work for our reaction with benzylamine (Table 1, entry 22).…”

NiO nanoparticles catalyzed three component coupling reaction of aldehyde, amine and terminal alkynes

“…In recent years, great efforts have been made with the C-H bond activation reaction of terminal alkynes. The C-H bond of alkynes can be activated by employing various homogeneous transition metal catalysts such as Ag I salts [19], Au III salen complexes [20], Au/ CeO 2 [21], Cu I salts [22], Fe III salts [23], Zn salts [24], Hg 2 Cl 2 [25], InCl 3 [26], and InBr 3 [27]. These catalysts are expensive and suffer from one or more drawbacks such as longer reaction time and difficulty in recovery of the catalyst.…”

A general A³: coupling reaction based on functionalized alkynes

“…It is also applicable to various substrates. This transformation can be catalyzed by a large number of transition-metal salts, including copper, 4 iron, 5 cobalt, 6 nickel, 7 zinc, 8 ruthenium, 9 silver, 10 cadmium, 11 indium, 12 ytterbium, 13 iridium, 14 gold, 15 mercury, 16 bimetallic salt combinations, 17 supported metals, 18 and nanostructured materials. 19 It is interesting to note that, although the use of various amines and aldehydes in this method has been described, the number of alkynes used has been limited.…”