Aldehyde-alkyne-amine

REACTIONS CATALYZED BY COPPER, SILVER, OR GOLD 12.2.1 Aldehyde-Alkyne-Amine Coupling... 

Wei C, Li Z, Li CJ (2004) The development of A -coupling (aldehyde-alkyne-amine) and AA -coupling (asymmetric aldehyde-alkyne-amine). Synlett 1472-1483 Bariwal JB, Ermolat ev DS, Van der Eycken EV (2010) Efficient microwave-assisted... 

X. Yao, C.-J. Li, Org. Lett. 2005, 7, 4395-4398. Phosphine-triggered complete chemo-switch from efficient aldehyde-alkyne-amine coupling to efficient aldehyde-alkyne coupling in water. 

P. Li, L. Wang, Y. Zhang, M. Wang, Tetrahedron Lett. 2008, 49, 6650-6654. Highly efficient three-component (aldehyde-alkyne-amine) coupling reactions catalyzed by a reusable PS-supported NHC-Ag(I) under solvent-free reaction conditions. 

M. Wang, P. Li, L. Wang, Eur. J. Org. Chem. 2008, 2255-2261. Silica-immobilized NHC-Cu(I) eomplex an efficient and reusable catalyst for A3-coupling (aldehydes-alkyne-amine) under solventless reaction conditions. 

Finally, two reports describing the use of polymer-supported NHC-Ag compounds in three-component aldehyde-alkyne-amine reaction and Suzuki coupling have been published. " ... 

The A (aldehyde-alkyne-amine) coupling reaction represents a benchmark transformation to evaluate the catalytic activity of new NHC-Ag complexes. A variety of propargyl amines were efficiently synthesized by this method in the presence of diverse NHC-Ag complexes. In some cases, supported catalysts allowing recycling could also be used without loss of efficiency. ... 

Examples of the protection of alkynes, carboxylic acids, alcohols, phenols, aldehydes, amides, amines, esters, ketones, and alkenes are also indexed on p. xvii. Section (designated with an A 15A, 30A, etc.) with protecting group reactions are located at the end of pertinent chapters. 

The coupling reactions of alkynes and aldehydes catalyzed by iron(III) salts have been discussed above (Scheme 10, routes B and C). The three-component coupling of aldehydes, alkynes, and amines is equivalent to the coupling reaction between alkynes and imines. Wang et al. reported such a three-component coupling catalyzed by FeCls in the absence of any ligand (Scheme 17) [33]. 

Scheme 19 Synthesis of quinolines by iron(III)-catalyzed three-component coupling/hydroaryla-tion of aldehydes, alkynes, and amines...

Catalytic coupling reaction of aldehydes, alkynes, and secondary amines promoted by less than 3 mol.% of Ag(l) salt was reported by Li et al,517 In this reaction, pure water was used as solvent and Agl was found to be the best catalyst without need of any additives or co-catalysts (Table 9). The reaction mechanism has been proposed as shown in Scheme 110. 

CuOTf/PyBox System The first direct asymmetric addition of alkynes to imines, generated from aldehydes and amines in situ, was reported by using copper salts in the presence of chiral PyBox ligand (Scheme 5.2). The products were obtained in good yields and excellent enantioselectivities in most cases. When toluene was used as solvent, up to 93% yield and 99% ee were obtained. Up to 99.5% ee was obtained when the reaction was carried out in 1,2-dichloroethane. The reaction can also be performed in water smoothly, and good enantioselectivities (78-91% ee) were obtained. 

Scheme 5.2. Asymmetric addition of alkynes to imines generated from aldehydes and amines.

Gold has even shown its ability as a nucleophile activator in three-component reactions of terminal alkynes, aldehydes and amines [186]. In the case of chiral amines, excellent diastereoselectivities were obtained [187] (Scheme 8.29). ... 

Solvent-Free Three-Component Coupling of Aldehyde, Alkyne and Amine 213... 

Li and coworkers have reported a novel silver-catalyzed, three-component coupling of an aldehyde, an amine, and an alkyne, and the first example of a direct addition of a silver acetylide to an aldehyde to produce propargylic alcohols (Scheme 1.41).103-105 Treatment of an aldehyde with a silver halide and secondary amine gave propargylic amines in good yields in organic solvent, water, or ionic liquids. The proposed mechanism suggests addition of a silver acetylide to the iminium ion formed in situ. 

In a closely related reaction, Li et al.101 devised a silver-catalyzed three-component coupling between aldehydes, alkynes, and amines. This transformation was really efficient in water and in an ionic liquid, although both required overnight heating at 100°C (Table 10.6). In this reaction, a silver acetylide that was sufficiently nucleophilic to add to the iminium ion that formed by condensation of the amine on the aldehyde was certainly produced.8... 

The coupling of the three components -aldehyde, alkyne and amine- has been called A3 coupling. 7 It delivers propargyl amines, which are important synthetic intermediates and, in contrast to previously used routes, avoids the use of strong-base reagents such as BuLi, ethylmagnesium bromide or LDA, and the need for the kinds of solvents necessary for these reagents. 

Halides are second only to carboxylic acids in their versatility in organic synthesis. Functional group transformations into alkenes, alkynes, amines, aldehydes, alcohols, ethers, hydrocarbons, ketones and other groups may be performed with ease in high yield. However, the major synthetic importance of halides arises from the ease by which compounds that contain this functionality may be used in carbon-carbon bond-forming reactions and in the preparation of heterocyclic compounds. 

Li and co-workers374,374a reported the three-component coupling reaction of an aldehyde, an amine, and a terminal alkyne catalyzed by a silver salt in water. Of various precatalysts examined, water-insoluble silver iodide gave the highest yields of the propargyl amines 452 (Scheme 137). The reaction probably proceeds via attack of a silver acetylide, generated in situ from the silver salt and the alkyne, to the iminium ion derived from the aldehyde and the... 

Various aliphatic aldehydes, alkynes and dialkyl amines have been coupled using silver(I) iodide as catalyst in [C4Ciim][BF4] with moderate to excellent yield, as illustrated in Scheme 9.8.[34] The nature of the aldehyde has a much greater influence on the outcome of the reaction in the ionic liquid than in water. With aliphatic aldehydes, the reaction proceeded cleanly with hardly any trimer formation whereas aromatic aldehydes afforded complex product mixtures. 

A Grignard type of addition of alkynes to in situ generated imines from aldehyde and amines, catalyzed by CuBr, provides an efficient solvent-free approach for the synthesis of substituted N-heterocycles such as propargyla-mines in excellent yields (Scheme 8.17). ... 

Propargylic amines. To assemble 1-alkynes, aldehydes, and amines into propargylic amines the heating with a AgNOs/zeohte catalyst is a convenient method. ... 

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