Aldehyde-alkyne-amine coupling reactions

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. 

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. ... 

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

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 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 17 Iron-catalyzed three-component coupling reactions of aldehydes, terminal alkynes, and amines...

To check the scope of this coupling reaction, a study with different combinations of aldehydes, amines, and terminal alkynes was performed. Aromatic alkynes turned out to be more reactive than aliphatic ones. This study included aliphatic... 

Interestingly, the alkenylation of sp3 C-H bond is observed in the iridium-catalyzed coupling reaction of aldehydes, amines, and alkynes (Equation (56)).62... 

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. 

Indium-Catalyzed, Three-Component Coupling Reactions of Aldehydes, Amines and Alkynes 253... 

When the secondary amine 33 was used instead of a primary amine, a different type of three-component coupling reaction took place with aldehyde 34 and 1-alkynes 35 to afford the corresponding allylamines (36 and 37) [22]. In this reaction, Ir-hydride generated by amine (33) with Ir, would be a key intermediate. The reaction may proceed by addition of the Ir-hydride to the enamine derived from amine 33 and alkyne 34, followed by insertion of aldehyde and dehydration to give the coupling product (36 and 37). 

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... 

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. 

Highly functionalized olefins are easily accessible via silyformylation of alkynes. When coupled to other reaction systems, silylformylation reactions become even more powerful. Eilbracht et al. demonstrated that stabilized phosphorous ylides 74 could be trapped by P-silylated a-P-unsaturated aldehydes formed via silylformylation of alkynes in a one-pot synthesis. The tandem reaction proceeds with high yields for both alipathic and aromatic terminal alkynes. Protected propargyl alcohols also showed good reactivity however, propargyl amines react with low selectivity. The reaction shown below is the best-afforded result for this process. ... 

S.4.2.4 Modifications of A -CoupUng Related coupling reactions in which one of the A -coupling substrates (aldehyde, amine, or alkyne) is replaced by other molecule affording mechanistically similar processes have recently appeared. Thus, as mentioned earlier (Scheme 3.41), the aldehyde component can be replaced by a ketone to give propargylamines bearing a quaternary carbon center [91, 136]. 

A -Coupling and Related Reactions Three-component coupling of aldehydes, alkynes, and amines (A -coupling) is a powerful methodology for the synthesis of propargylamines [88], which has been widely explored using Cu-, Ag-, or Au-based catalysts (see Section 3.4.2). 

M. Kidwai, V. Bansal, A. Kumar, S. Mozumdar, Green Chem. 2007, 9, 742-745. The first Au-nanoparticles catalyzed green synthesis of propargylamines via a three-component coupling reaction of aldehyde, alkyne and amine. 

P. Li, Y Zhang, L. Wang, Chem.-Eur. J. 2009, 15, 2045-2049. Iron-catalyzed ligand-free three-component coupling reactions of aldehydes, terminal alkynes and amines. 

In a related reaction, a 3-components coupling of alkyne, amine and aldehyde proved to be best catalyzedby Agl while AgOTf was less efficient (80% versus 40%) (eq 56). ... 

---