The synthesis of propargylamines via A3 coupling mostly under metal-catalyzed procedures is well known. This work invented an unprecedented effect of salicylaldehyde, one of the A3 coupling partners, which could lead to the formation of propargylamine, an important pharmaceutical building block, in the absence of any metal catalyst and under mild conditions. The role of the hydroxy group in ort...

Trifluoromethyl propargylamines react with various azide derivatives to afford 1,4-disubstituted 1,2,3-triazoles through a Huisgen 1,3-dipolar cycloaddition. The reaction is catalyzed by a Cu(I) species in acetonitrile, and the corresponding products are obtained in good yields. This process thus offers an entry to new trifluoromethyl peptidomimetics as interesting scaffolds.

FeCl(2) catalyzes the oxidative C-C cross-coupling of tertiary amines with terminal alkynes into propargylamines using (t-BuO)(2) as oxidant. The reaction can be applied to aromatic and aliphatic amines and alkynes without solvent. High chemoselectivity for aminomethyl groups is due to a steric factor.

Mono- and 1,3-disubstituted allenes were synthesized from the corresponding propargylamines via palladium-catalysed hydride-transfer reaction. In the current transformation, propargylic amines can be handled as allenyl anion equivalents and introduced into various electrophiles to be transformed into allenes under palladium-catalyzed conditions.

An iron(III)-catalyzed three-component coupling reaction of alkynes, CH(2)Cl(2) and amines was developed for facile synthesis of propargylamines. Preliminary mechanism investigation using in situ FT-IR reveals that the crucial Fe-acetylide intermediate could be formed through C-H bond activation of alkynes thanks to cooperative effect of FeCl(3) and 1,1,3,3-tetramethylguanidine.

A general synthesis of 3-amidoindoles from easily available arylhydrazines and acylated propargylamines is described. In the presence of inexpensive Zn salts, alkyne amination and subsequent Fischer indole-cyclization took place in good yields with excellent regioselectivity providing an interesting scaffold for potentially bio-active compounds.

A Cu(I)-catalyzed direct addition of alkynes to imines was developed. The process is simple and provides a diverse range of propargylamines in high enantiomeric excess and good yield both in water and in toluene. The absolute configuration of such addition products has been determined by x-ray crystallography.

2-Phenallyl was found to be a versatile protecting group of primary amines for the asymmetric one-pot three-component synthesis of propargylamines which leads to enantiomeric excess of up to 96%; it can be easily removed with a palladium(0)-catalyzed allylic substitution using 1,3-dimethylbarbituric acid as a nucleophile.