Phosphorus-centered Radicals Induced Bifunctionalization Of Alkenes

Ever since the discovery of free radicals at the beginning of last century,great achievements have been accomplished with this kind of species.With the development and emergence of new synthetic methods in organic chemistry,the research on free radical chemistry has evolved rapidly.This has led to great understanding of radicals and radical reactions.The traditional view is that free radicals are too reactive,highly unstable,and uncontrollable and therefore lack selectivity.In recent years however,research has demonstrated that free radicals could be relatively stable under suitable conditions.As a result,free radical reactions can be controlled and as well be highly selective.Many functional groups can also be tolerated without any additional protection.Reactions involving free radicals have been widely applied in organic synthesis,asymmetric synthesis and material synthesis.The use of organic free radicals for the development of green,efficient and highly selective synthetic methods has great significant value in theory and potential application.This study focuses mainly on the direct C_sp2-H radical methylation/thifluoromethylation reactions and phosphonyl radical mediated difuntionalization of carbon-carbon double bonds.This thesis has been divided into two parts as described below.1.Studies on C_sp2-H methylation/trifluoromethylation of pyrimidones and pyridonesMethylation and trifluoromethylation reactions have attracted wide attention since the introduction of a methyl or trifluoromethyl group into a molecule can significantly alter its chemical properties and bioactivity.On this basis,the direct C_sp2-H methylation and trifluoromethylation of pyrimidones and pyridinones were studied.?a?Methylation of pyrimidones and pyridones.Methyl radicals were generated from the decomposition of dicumyl peroxide?DCP?under the influence of heat.The methyl radical selectively added to the?-positions of pyrimidones and pyridones to produce a carbon-centered radical intermediate.The intermediate was oxidized by DCP to form the corresponding methylated pyrimidones and pyridones.This protocol offers a new,simple and efficient route to 5-methylpyrimidones and 3-methylpyridones.Moreover,a 50g-scale reaction was performed and the reaction proceeded smoothly to afford the desired product in 70%yield.?b?Trifluoromethylation of pyridonesSodium trifluoromethanesulfonate was oxidized by Mn?OAc?₃ to generate trifluoromethyl radicals.Trifluoromethyl radical selectively adds to the?-position of pyridones to afford a series of 3-trifluoromethyl pyridones.2.Studies on phosphorus-centered radicals-mediated difunctionalization of C=C bondsDifunctionalization reaction is an efficient type of reaction involving the simultaneous introduction of two different groups into one molecule.Phosphorus-centered radicals were generated under suitable conditions and subsequent addition of these radicals to C=C bonds results in the formation of a carbon-centered radical intermediate.The intermediate further reacted with radical acceptors to form the desired products.Alternatively,the intermediate was oxidized to give a carbocation which reacted with nucleophilic reagents to afford the products.Under the guidance of this strategy,the reactions below were carried out.?a?Studies on phosphorus-centered radicals mediated phosphorylation-oximation reaction of alkenesThis study is based on AgNO₃-catalyzed generation of phosphonyl radicals,and their subsequent reaction with alkenes and tert-butyl nitrite.Studies showed that phosphorus-centered radicals could be effectively generated in the presence of AgNO₃in an ethanol/water system.The phosphorus-centered radicals reacted with alkenes to form a carbon-centered radical intermediate.This radical intermediate was trapped by nitric oxide,formed instantly in the reaction system,to give an intermediate,which underwent rearrangement to give the phosphorylation-oximation product.This mild method provides a novel and efficient access to?-phosphorylketoxime derivatives in moderate to high yields.Besides,the products obtained can be further transformed into many other vital compounds.?b?Studies on phosphorus-centered radicals mediated cyano-phosphorylation of alkenesThis work focused on the copper catalyzed reaction of phosphorus-centered radicals with alkenes,and trimethylsilyl cyanide.Phosphorus-centered radicals were effectively generated in the presence of Mn?OAc?₃·2H₂O.Then,these radicals reacted with alkenes to form a carbon-centered radical intermediate.This radical intermediate further reacted with trimethylsilyl cyanide in the presence of CuCN to afford the desired phosphoryl-cyanation product.This reaction provided a novel and convenient method of preparing?-cyanophosphorylated compounds.?c?Studies on phosphorus-centered radicals mediated thiocyano-phosphorylation of unsaturated bondsThis work is based on the reaction of phosphorus-centered radicals with alkenes and trimethylsilyl isothiocyanate in the presence of CuBr₂ catalyst.The phosphorus-centered radicals were generated in the presence of Mn?OAc?₃·2H₂O,which reacted with alkenes to form a carbon-centered radical intermediate.This radical intermediate further reacted with trimethylsilyl isothiocyanate in the presence of CuBr₂ to afford the desired thiocyano-phosphorylation product.This reaction provided a novel,convenient and highly efficient method of preparing?-thiocyanoalkenyl phosphorylated compounds.Finally,westudiedthephosphorus-centeredradicals-mediated difunctionalization reaction of phenylacetylene.With this strategy,the first thiocyano-phosphorylation of alkynes was realized,thus providing a novel strategy of synthesizing?-thiocyanoalkenyl phosphorylated compounds.