| Halo compound is of great importance in different disciplines due to the rich carbon-halogen bonds therein.This compound is ubiquitous in nature,and it is widely applied in the fields of medicinal chemistry,chemical biology,materials chemistry,and synthetic chemistry.Therefore,the preparations and transformations of carbon-halogen bonds are still the focus of synthetic chemistry.Due to the unique reactive activity of the α-position of the carbonyl group,the construction of carbon-halogen bonds at theα-position of the carbonyl group has been a hot topic in synthetic chemistry.On the other hand,because of the easily polarizalility and weakly bond strength of carbon-halogen bonds,the cleavage of these cabon-halogen bonds is a concise and important synthetic strategy in organic synthesis,resulting in structurally diverse and functionally important organic molecules.Among of them,thioamide has been widely used in biology,materials,and synthetic chemistry due to its unique physical and chemical properties.In this thesis,we focused on some useful chemical transformations involving carbon-halogen bond in organic synthesis.One is the cleavage of carbon-halogen bonds to synthesize various thioamides,the other is the construction of carbon-halogen bonds at the α-position of the carbonyl group using various F,Cl,and Br sources.This thesis includes the following four chapters:Chapter 1: Because of the wide application of thioamides in the fields of biochemistry,medicinal chemistry,materials chemistry and synthetic chemistry.numerious synthetic methodologies for preparation of thioamide have been extensively investigated from synthetic chemists.In this chapter,the relative synthetic approaches toward thioamides have been classified and summarized in detail.Chapter 2: Due to its unique physical,chemical,and biological properties,thioamide has been widely used in different research fields,consequently,a number of synthetic methods have been explored.However,some shortcoming still existed in the repoted,therefor the development of efficient synthetic method is still highly desired.In this section,after extensive investigations of reaction oxidants,sulfur sources,solvents,and temperatures,a novel and straightforward method for the preparation of thioamides has been developed.Notably,to our best knowledge,this thio-Ritter reaction has been explored for the first time.The current transformation features wide substrate scope,good yields,and easily available starting materials.Meanwhile,latestage thioamidation of the bromo derivatives of active pharmaceutical ingredients and fragrance have also been realized.A possible mechanism was proposed based on some designed control experiments.Chapter 3: α-Halo ketone is not only frequently found in functional molecules,but also widely used as an important organic synthons,hence,the preparation of this unit has attracted attentions from synthetic chemists.In this part,the construction of carbonhalogen bonds at the α-position of the carbonyl group has been achieved using iron(III)chloride and iron(III)bromide as halogen sources with phenyliodonium diacetate as oxidant under the mild reaction conditions,and the present protocol could also be applied for the preparation of α-chlorinated/α-brominated ketones on gram-scale.It should be mentioned that the antithrombotic clinical drug prasugrel was synthesized at a gram scale with a total yield of 30% in three steps using this developed method as a key step.According to the control experiments,a possible reaction mechanism was proposed.In addition,the synthesis of geminal dihalocarbonyl compounds has also been preliminary studied using this developed halogenation method.Chapter 4: Due to the switchable lipophilicity,bioavailability and metabolic stability of florine atom,therefore,the preparation of these compounds containing florine atom has receives attracted attentions from synthetic chemists,especially the molecules bearing a fluorine-containing quaternary stereocenter.In this section,the construction of the challenging quaternary C–F bond has been achieved using cheap ptoluenesulfonic acid as the acidic catalyst and Selectfluor as the fluorination reagent under the mild reaction conditions.Meanwhile,the present protocol could be applied for the preparation of α-fluorinated ketones on gram-scale.More importantly,late-stage fluorination of natural products has also been realized. |
