Applications Of Enaminones In The Synthesis Of Nitrogen-containing Heterocycles

For the past decades, enaminones have emerged as versatile synthetic intermediatesm because they combine the ambident nucleophicity of enamines with the ambient electrophilicity of enones. The pyrrole, oxazoles, pyridinones, quinolines, dibenzodiazepines, tetrahydrobenzoxazines and tetronic acids have been prepared from enaminones. Enaminones are also valuable precursors forα-iodol enaminones, 3-amino sugar derivatives, azo-compounds,β-aminoketone, as well as tetrahydropentalenes, tetrahydroindenes, and hexahydroazulenes.2-pyridones derivatives are important nitrogen-containing heterocycles and applied in many arrears, such as dyestuff, medicine and agricultural chemicals. In addition, 2-pyridones derivatives are important catalyst in the synthesis of ethyl alcohol, the acetaldehyde and polyimides. Recent years have seen a resurgence of interest in the development of stereo- and enantioselective methodologies.Currently, cancer is one of the focal points that human pay attention to. The development of anticancer agent's research directly decide the development of this domain, therefore many researchers devote to the anticancer agent's research.Cyclophosphamide is one of the clinical application anticancer drugs, but it is high toxic and low stability and its application is limited. Therefore, the research to modify and remold the structure of this compounds is still very important.Combining with the special properties of enaminones, we focus on its applications in the synthesis of nitrogen-containing heterocycles. This work mainly based on the following four aspects:1. We synthesized enaminones.2. A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.3. We developed a facile and efficient one-pot synthesis of polysubstituted pyridin-2(1H)-ones from a variety ofβ-oxo amides under Vilsmeier conditions, and a mechanism involving sequential halogenation, formylation and intramolecular nucleophilic cyclization is proposed.4. A facile and efficient one-pot synthesis of substituted cyclophosphamidic chlorides and their analogues has been developed from readily available enaminones, 2-arylamino-3-acetyl-5, 6-dihydro-4H-pyrans.In summary, a facile and convenient one-pot synthesis of polysubstituted pyridin-2(1H)-ones and cyclophosphamide analogues was developed. The simplicity of execution, mild conditions, high yields, ready availability of substrates, flexible substituted patterns, and broad range of potential synthetic utility of the products, make the protocol attractive for academic research and practical applications.