Synthesis Of 2-phenyl Oxazole Derivatives And α-bromom Methyl Ketones By Gold Catalysis

Through the development in the past decades, the homogeneous gold catalyst has become one of the hot issues in research of catalysts. Since both Au (Ⅰ) and Au (Ⅲ) have favorable capability to activate alkyne, they can make the triple bond take in attacks of various nucleophiles and generate heterocyclic rings and heteroatomic compounds.This paper researches application of the intermediate, α-oxo gold carbene, generated intermolecular oxidation alkynyl in gold catalysis, in synthesis of heterocyclic rings and heteroatomic compounds. The research includes the following two parts:Firstly, a new approach to generate 2-phenyl oxazoles is proposed through gold catalyzing and oxidizing terminal alkyne to generate the intermediate, α-oxo gold carbene and dibroethane. The reaction is a [2+2+1] annulation of a terminal alkyne, a nitrile, and an oxygen atom from an oxidant. The effects of catalysts, acid, temperature and oxynitrides on yields of the reaction have been evaluated, and further the optimum condition for reaction is selected.5mol% Ph3PAuNTf2 is used as the catalyst and 1.3 equiv 8-methylquinolinenitrogen oxygen is apllied as oxidant to catalyze the reaction of terminal alkyne and cyanobenzene, successfully synthesizing a series of 2-phenyloxazole derivatives at 60℃, the highest yield of these compounds was up to 90.3%.Cytotoxicity has been studied by using a MTT assay to identify Bel-7402, MCF-7, A549 and Hela still active in respiration. It is shown that products exhibit cytotoxicity to Bel-7402 cells; especially,2c treated with the cells shows lower cytotoxicity (IC50:10.2μg/mL) than free paclitaxel (28.0μg/ml). We have preliminarily investigated anticancer mechanism of products using Bel-7402 cells by Hoechst-PI dual staining method. From cell morphology initial analysis, apoptosis mechanism of synthesized products may induce cell death.Secondly, a good way to generate α-bromom methyl ketone is proposed through gold catalyzing and oxidizing terminal alkynes to generate the intermediate, α-oxo gold carbene and dibroethane. In the experiment, impact of acid, temperature and different gold catalysts on reaction yield is investigated, and further the optimum condition for reaction is selected. In room temperature, in the condition that 4mol% Cy3PAuSbF6 as catalyst, and 1.3 equiv 8-methylquinolinenitrogen oxygen as oxidant, terminal alkynes and dibroethane were reacted, which prepared a series of target compounds, and the highest yield of these compounds was up to 87.3%. In order to study the way whether fit other compounds, the author ues terminal alkynes and diiodoethane as substrate and toluene as solvent to generate a series of α-iodo methyl ketones with high yield, which the highest yield was up to 67.3%. At the same time, this is a new method to synthesis the α-iodo methyl ketones.