The Synthesis Of Fluoromethylthioesters And A Core Tetracyclic Framework Of Monoterpene Indole Alkaloids

The dissertation focuses on the synthesis of difluoromethylthioesters,monofluoromethylthioesters and a core tetracyclic framework of monoterpene indole alkaloids.It is made up of four chapters.Chapter 1.Recent Advances on the Synthesis of SCF2H-and SCH2F-Containing Molecules.Owing to the unique features of difluoromethylthiol?-SCF₂H?and monofluoromethylthiol?-SCH₂F?groups,and their tendencies to modify physical and chemical properties of biological active molecules,their incorporation is a matter of importance for the discovery of new pharmaceuticals and agrochemicals.This chapter highlights the recent advances on the synthesis of SCF₂H-and SCH₂F-containing molecules,and summarizes the types of these compounds.Chapter 2.Synthesis of Difluoromethylthioesters from Aldehydes.The SCF₂H group has drawn exceptional attention from chemists and pharmacologists because of its unique physical and chemical properties.However,to the best of our knowledge,the reports are limited to difluoromethylthioethers so far.Difluoromethylthioester compounds are yet another important kind of organofluorine compound and are reported here for the first time.They can be efficiently synthesized from various aldehydes,employing tert-butyl hydroperoxide as the radical initiator and acetonitrile as the solvent.The synthetic method features mild reaction conditions,good tolerance of functional groups,broad substrate scope including?hetero?aromatic aldehydes,aliphatic aldehydes,and?,?-unsaturated aldehydes,and importantly,no metal is involved in the reaction.Preliminary mechanism studies supports the radical process of the transformation.The approach has the potential to become an important tool for the late-stage functionalization of advanced synthetic intermediates.Chapter 3.Synthesis of Monofluoromethylthioesters from Aldehydes.Monofluoromethylthioesters have drawn remarkable attention from chemists and pharmacologists because of its unique biological properties.In the literature,monofluoromethylthiolesters were synthesized mainly through an indirect approach employing acids as the starting materials throught two or more steps.Despite these processes being effective,the disadvantages of them are apparent,including safety issues,high expenses,and environmental problems.In this chapter,a direct and efficient approach to the synthesis of monofluoromethylthioestersfromaldehydeshasbeendeveloped,employing azobisisovaleronitrile as the radical initiator and 1,2-dichloroethane as the solvent.The synthetic method features mild reaction conditions,good tolerance of functional groups,a broad substrate scope including?hetero?aromatic aldehydes,aliphatic aldehydes,and?,?-unsaturated aldehydes,and especially no metal involved in the reaction.Chapter 4.Studies on the Synthesis of a Core Tetracyclic Framework of Monoterpene Indole Alkaloids.The ABCD tetracyclic framework is the core structure of many monoterpene indole alkaloids,most of which show multiple biological activities.Due to its unique spiral structure and two consecutive chiral centers,the construction of the tetracyclic framework has been a hot topic in the field of organic synthesis.Firstly,this chapter summarized the previous synthetic methods of such tetracyclic framework.Then the chapter described our researches on the synthesis of the tetracyclic framework with a new synthetic strategy.Our synthesis started from commercial materials,indole,furfural and p-toluenesulfonamide,and underwent three key steps:1)Asymmetric Friedel-Crafts reaction of indoles with imines catalyzed by a cinchona alkaloid to form the first chiral center;2)a furan ring opening reaction to provide all the carbon atoms needed for the D-ring;3)A sequential one-pot S_N2/intramolecular aza-Baylis-Hillman reactions to construct CD-rings.The first two key steps have been accomplished,and a lot of exploratory experiments have been carried out on the third key step.Further investigations on the third key step are ongoing.