Studies On The New Method Of Synthesis Of β-Enamino Ketones

β-Enamino ketones are a kind of important pharmaceutical intermediates, and their chemistry has drawn considerable attention in recent years.β-Enamino ketones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident electrophilicity of enones, and have been extensively used for the preparation of a variety of heterocyclic derivatives including some natural products and analogues, such as indoles, pyridines and pyrroles; In coordination chemistry, enaminones can be used as good chelating ligands for main group metals and transition metals; Moreover, someβ-Enamino ketones exhibit very extensive pharmacological effects, especially in convulsions, malaria, antiviral treatment of cardiovascular diseases.At present, there are dozens of ways to synthesizeβ-Enamino ketones, including: (1) The condensation ofβ-diketones with amines catalysed by Lewis acid; (2) The condensation of ketones with DMFDEA, while xylene is used as reaction solvent; (3) Coupling of acid chlorides with terminal alkynes, and followed by subsequent addition of amnines access toβ-Enamino ketones, this procedure is catalysed by Pd(Ph3)2Cl2; (4) Decomposition of heterocyclic compounds to affordβ-Enamino ketones, however, the reaction is always associated with many side reactions. What's more, expensive raw materials, toxic solvents, harsh reaction conditions, longer reaction time and other shortcomings are used in those synthetic routes.This paper has developed a new procedure, in which hydroxymethylene was used as the key intermediate, to synthesizeβ-Enamino ketones via two- step reactions. We have investigated a variety of reaction factors on the yield and got the optimized conditions: In the first step, ether is used as the solvent, sodium ethoxide as the catalyst, the ratio of acetophenone and ethyl formate is 1: 2, the reaction tempretrue is 25oC; In the second step, water as the solvent, the ratio is 1: 2.Fifteenβ-Enamino ketones were synthesized via the new procedure, including eight aliphatic enaminones, six aromatic enaminones and a enamine nitrile. All those structures were determined by IR, MS and 1H-NMR. we have studied chemical selectivity and enantioselectivity of the new procedure based on NMR data and single crystal diffraction data.The result of experiment indicates that the aryl-substituted ketones with electron-donating groups could afford excellent yield by the new procedure. The chemoselective increased with the increase of the steric hindrance of the substituent. The enantioselectivity of the new procedure is high, and theβ-Enamino ketones synthesized in this paper are all trans structures.