Grignard Reagents Promoted Regioselective Addition Of Diketones And Its Applications

Grignard reagents have been widely used as substrate in various types of organic reactions,and some of them have been used in industry.However,there are few reports on Grignard reagents' usage as a promoter which plays the catalyst-like role in organic reactions.Furthermore,Grignard reagents promoted regioselective addition of diones have not been reported so far.In this paper,isopropyl magnesium chloride-promoted regioselective addition of diketones and its applications were deeply and extensively studied.The reaction mechanism was discussed in detail to explain the high regioselectivity by chemical experiments,hydrogen-deuterium exchange and mass spectrometry.Also,the anti-lung cancer activity and antibacterial activities of the products were tested.There are seven portions in this dissertation.In chapter one,research status and the applications of Grignard reagents are summarized.In chapter two,i-PrMgCl promoted regioselective addition of Grignard reagents to linear 1,3-diketone were studied.The results showed that i-PrMgCl can efficiently promote the reaction to afford a series of hydroxy-2-ketones in one step with high yield.The amplification of this procedure(gram scale)was studied,which indicates its practical application value.In chapter three,i-PrMgCl promoted regioselective addition of Grignard reagents to cyclic 1,3-diketones were studied.The results showed that i-PrMgCl can efficiently promote the reaction and a series of 3-substituted cycloenones were gained in one step with high yield.The amplification of this procedure(gram scale)was also studied,it went smoothly with no loss of yield,which indicated its practical application value.In chapter four,the reaction mechanism of the regioselective addition mentioned above was explored in detail to explain the high regioselectivity by chemical experiments,hydrogen-deuterium exchange and mass spectrometry.A rare halogen exchange process was discovered for the first time and the important intermediates of the reaction were verified.In chapter five,according to the reaction mechanism put forward in chapter four,continuous one-pot reaction of the Grignard reagent with linear and cyclic diketones was achieved firstly.4-Hydroxy-2-ones and 3-substituted cycloenones were obtained simultaneous ly in one pot and the amount of i-PrMgCl was significantly reduced to half while their yields were as good as that in chapter two and three,thus the reliability of the inferred reaction mechanism in chapter four was confirmed.In chapter six,i-PrMgCl was used as promoter in the regioselective addition of isatin and its derivatives with 2-benzothiazoleacetonitrile.A series of 3-enyl-oxindole were gained in high yields.The biological activity of these products was tested.One compound performed high activity against the human lung adenocarcinoma cell(A549).Six products showed high activity against wild Bacillus subtilis and another one product showed high activity against Staphylococcus aureus.Three products showed high activity against methicillin-resistant staphylococcus aureus(MRSA).All of these compounds mentioned above deserve the further study.In chapter seven,i-PrMgCl was used as promoter in the regioselective addition of isatin and its derivatives to 4-hydroxycoumarin.A series of 3-enyl-oxindole were obtained.The biological activity of these products was tested.Three compound performed high activity against human lung adenocarcinoma cell(A549)and two products showed high activity against wild Escherichia coli.One product showed high activity against Staphylococcus aureus and another one product showed high activity against Escherichia.coli-NDM-1.These three compounds have the value for further research.In this dissertation,the application of Grignard reagents as efficient promoter in organic reaction was extended.i-PrMgCl showed excellent function in the regioselective addition of dione.All the results in this dissertation provide a solid foundation for further application of Grignard reagents.