Propargylamines, three component

Several new methods for the synthesis of the oxazole nucleus were published. A new consecutive three-component oxazole synthesis by an amidation-coupling-cycloisomerisation sequence was developed. The synthesis started from propargylamine 92 and acyl chlorides. To extend this process, a four component sequence involving a carbonylative arylation by substitution of one acyl chloride with an aryl iodide and a CO atmosphere was also performed <06CC4817>. 

A copper-catalyzed one-pot three-component atom-economical C-H functionalization process was used to form enantioenriched propargylamines. This protocol was also employed for the synthesis of the alkaloid (A)-(+)-coniine (Equation (196)).159 159a... 

Li and Wei have extended their Grignard-type methodology in water to the use of in. (////-generated imines from the corresponding aldehydes and arylamines, thus furnishing the corresponding propargylamines in a three-component one-pot procedure. 

Scheme 9.27. Enantioselective three-component reaction for the synthesis of propargylamines.

Knochel and co-workers [39] reported a related three-component reaction between various alkynes, aldehydes, and secondary amines in the presence of CuBr and (R)-quinap 149 to give the corresponding propargylamines in excellent yields and good enantioselectivities (Scheme 9.27). 

The scope of the Cu-catalyzed cycloaddition between propargylamines and electron-deficient olefins in the presence of catalytic amounts of a copper salt was subsequently expanded to a one-pot, three-component coupling strategy involving phenols as third components [65]. In this case, reactive Michael acceptors such as ethyl 2-aryl- or alkylsulfonyl cinnamates 57 are involved in the process. This sequence leading to 3(4)-phenoxymethyl pyrrolidines 60 and their isomeric pyrrolidines 61 comprises of the relay process of... 

Other nucleophiles that have been used in this context are acetylides (alkynes). The addition of those to iminium cations generated in situ from aldehydes and secondary amines accomplishes a gold(III)-catalyzed three-component coupling for the synthesis of propargylamines, as can be observed in equation (124). The reactions are performed in water or in tetrahydrofuran (THF) when supported catalysts are employed.Chiral prolinol derivatives as... 

A variety of propargylamines can be prepared by three-component Mannich condensation of acetylenes, aldehydes, and secondary amines (Scheme 7.19) [66, 67). These reactions were performed using CuCl to activate the acetylene component. Reaction times varied from 3-36 h. Silver iodide has recently been used to catalyze the reaction [68]. 

Gold nanoparticles on ZnO were used as a catalyst for the rapid one-pot three-component condensation of amines (106), aldehydes (107), and phenyl acetylene (20), affording the selective synthesis of propargylamines (108) at room temperature (Scheme 9.32) (Gonzalez-Bejar et al. 2013). Propargylic alcohols constitute important building blocks for many biologically active compounds and natural products. 

Gommermann N, Koradin C, Polbom K et al (2003) Enantioselective, copper(I)-catalyzed three-component reaction for the preparation of propargylamines. Angew Chem Int Ed 42 5763-5766... 

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. 

X. Zhou, Y. Lu, L.-L. Zhai, Y. Zhao, Q. Liu, W.-Y. Sun, RSC Adv. 2013, 3, 1732-1734. Propargylamines formed from three-component coupling reactions catalyzed by silver oxide nanoparticles. 

A. Bisai, V. K. Singh, Org. Lett. 2006, 8, 2405-2408. Enantioselective one-pot three-component synthesis of propargylamines. 

S. Nakamura, M. Ohara, Y. Nakamura, N. Shibata, T. Toru, Chem.-Eur. J. 2010, 16, 2360-2362. Copper-catalyzed enantioselective three-component synthesis of optically active propargylamines from aldehydes, amines, and aliphatic alkynes. 

N. Gommermann, P. Knochel, Chem. Commun. 2005,4175-4177. 2-PhenaUyl as a versatile protecting group for the asymmetric one-pot three-component synthesis of propargylamines. 

The Au- or Cu-catalyzed reaction primarily leads to N-aryl-2-propargylamines 130, whose cyclization to quinolines 132 requires additional dehydrogenation. This approach has been further developed to a sequential three-component process by combining aromatic aldehydes and primary amines with terminal alkynes catalyzed by AuCli/CuBr [189]. 

The enantioselective, catalytic, three-component Mannich-acetylene reaction is the most direct and economical way to afford chiral nitrogen-containing building blocks. In this field, a great development has been accomplished in the use of different chiral molecules as ligands for several copper(l) salts as catalyst for the synthesis of chiral propargylamines 39. Thus, the addition of phenylacetylene (22a, = Ph) to... 

Gommermann, N., Knochel, P. (2006). Practical highly enantioselective synthesis of propargylamines through a copper-catalyzed one-pot three-component condensation reaction. Chemistry - A European Journal, 12, 4380-4392. 

Akullian, L. C., Snapper, M. L., Hoveyda, A. H. (2003). Three-component enantioselec-tive synthesis of propargylamines through Zr-catalyzed additions of alkyl zinc reagents to alkynylimines. Angewandte Chemie International Edition, 42, 4244-4247. 

Both copper- and silver-catalyzed three-component reactions between an aldehyde, terminal alkyne, and secondary amine have been used to generate propargylamines [17, 18] The copper-catalyzed hydroamination between hydroxylamine esters and unactivated aUcenes generates amines with the desired regiochemistry for a wide range of diverse substrates [20]... 

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