Copper-Catalyzed Aminolysis of Beta, Beta-Dialkylthio Carbonyls with Ammonia: Synthesis of Enaminones with a Free Beta-Amino Group
Enaminones are a class ofβ-dicarbonyl enamines compounds and they synthesis have been actively developed in this recent years. They are still remaining a current subject in organic chemistry due to their multiples utility and applications. They are useful intermediates for the preparation of various heterocyclic and biological active compounds such as dopamine auto-receptor agonists, and acetylcholinestersase inhibitors, oxytocin antagonists and anticonvulsants. Several papers have been published relating their synthesis and their importance in organic chemistry, medical and pharmaceutical chemistry. Recent studies have revealed that some of the simpleβ-enaminones are biologically active and serve as leads for antibacterial agent development.
And as useful intermediaries, enaminones have considerable applications; these derivatives have been also extremely used for the preparation of variety of heterocyclic system including some natural products and analogues. Recently Kepe V and his coworkers have developedβ-dimethyl amino-a,β-unsaturated ketones and nitriles into pyridine, isoquinoline, pyrazole, isoxazole, pyrimidine and Pyranone derivatives which are very important and useful heterocyclic rings. Due to their wide range of activity and importance, a variety of methods for the synthesis of enaminones are published in the literature. Among the plethora of methods, the most attractive protocol is obviously the direct condensation of 1, 3-dicarbonyl compounds with amines.
A practical approach towards to the synthesis ofβ-enaminones was reported by Baraldi in 1983, in which the target compounds were made by refluxing 1,3-dicarbonyl compounds with amine or ammonium acetate in the presence of acetic acid in benzene with azeotropic removal of water. Since then several new protocols leading toβ-enaminone derivatives,in,which,AL2O3,SiO2,montmorillonite,KlO,1,3-diketonatoboron,difluorides,NaAu Cl4,Zn(C104)2, Bi(OCOCF3)3 and CeC.H2O were used as catalysts or as reagents have been published. Some new improvements as also been done; like the reaction of Dithioacetals with amines which afforded enaminones in good to excellent yields. Number of these methods presents the disadvantage of including not readily available reagents, high temperature and difficult accessible catalyst. It is noteworthy noticing that very few methods have been published leading the enaminones starting from readily available Dithioacetals. And on the other hand it must be noticed that most of these methods afford enaminones with secondary and tertiary amino group. Very little case has been reported for enaminones with free amino group.
As part of our ongoing research towards on the synthesis of enaminones we developed a facile method for the synthesis enaminones containing a free beta amino group. Therefore it has been known that this kind of compounds are difficult to prepare, and there are very few examples for the preparation of enaminones with free amino group which from a synthetic point of view are much more valuable functional group for manipulation. Not only that few efforts were made to synthesize enaminones with a free amino group also it has been reported in the few case the preparation of these compound starting from Dithioacetals as a substrate.
In summary, this work presents an easy way for the synthesis of enaminones containing a free amino group using Beta, beta-Dialkylthio carbonyls as starting materials in the presence of Cu (II) salts as catalyst.