Studies On Trifluoromethylthiolation And Electrophilic Cyclization Reactions

In this thesis,AgSCF3 promoted trifluoromethylthiolation-cascade cyclization reactions and acid catalyzed or electrophile promoted cascade cyclization reactions of propynols(or propynones)have been studied,including the following six chapters: Chapter OneIn the first chapter,the development of trifluoromethylthiolation reaction was introduced.According to the nature of reagents,the trifluoromethylthiolation reaction can be summarized as: radical type,electrophilic type,nucleophilic type,transition-metal-catalyzed coupling or C-H activation,and multi-component trifluoromethylthiolation reaction.The radical trifluoromethylthiolation reaction is mainly initiated by the use of SCF3? radical generated from AgSCF3 with persulfates.The electrophilic trifluoromethylthiolation reaction is primarily conducted with several N-SCF3 or O-SCF3 reagents,including trifluoromethylthiolation of boric acids,terminal alkynes,olefins,?-ketoesters and carboxylic acids.The nucleophilic trifluoromethylthiolation agents mainly include salts containing SCF3-anions,which could introduce the trifluoromethylthio group into the target molecules in the presence of Lewis catalysts.In the presence of transition-metal catalysts,aryl halides can be conducted with many nucleophilic trifluoromethylthiolation agents through coupling reactions,or the trifluoromethylthio group can be introduced by C-H activation under the guidance of directing groups.The sulfur and fluorine in the trifluoromethylthio group may also be provided by elemental sulfur and TMSCF3 respectively as the multi-component trifluoromethylthiolation reaction.Chapter TwoIn the free radical reactions,olefins are more likely to capture free radicals than alkynes to produce alkyl radicals.So reactions triggered by a carbon-carbon triple bond in a radical pathway would be more difficult with drastically reduced yields.Since 1,6-enyne has multiple reaction sites,it is envisaged that olefinic moiety in 1,6-enyne substrate could be attached to hindered groups,forcing the initiation of this reaction from the triple bond.In this chapter,a C-SCF3 bond and two C-C bonds were successfully constructed in one reaction step to synthesize a series of trifluoromethylthio-substituted fluorene derivatives,which is also the first report on trifluoromethylthiolation-cascade cyclization reaction triggered by a carbon-carbon triple bond in a radical pathway.Chapter ThreeIn the third chapter,BF3·OEt2?AgSCF3 promoted trifluoromethylthiolation-cascade cyclization reaction of propynols was developed in the presence of SCF3-anion from AgSCF3.This reaction occurred smoothly with C-SCF3 bond and C-O/N bonds constructed concurrently under mild conditions in good to excellent yields(up to 99%)for the synthesis of a lot of trifluoromethylthio-substituted 2H-chromene and 1,2-dihydroquinoline derivatives.Chapter FourIn the fourth chapter,various acid catalyzed or electrophile promoted cascade cyclization reactions of propynols(or propynones)were briefly summarized.Firstly,Meyer-Schuster rearrangement reaction and the design of cascade cyclization reactions based on Meyer-Schuster rearrangement were introduced.The main process of cascade cyclization reaction of propargyl alcohol involves:(i)the removal of hydroxyl group of a propynol gives propargylic cation intermediate in the presence of an acid or electrophile;(ii)the subsequent rearrangement of propargylic cation intermediate affords allenic cation intermediate;(iii)the attack of nucleophile in the reaction system onto the allenic cation intermediate generates allene intermediate;(iv)finally,other nucleophiles would attack the carbon of the allenic cation intermediate to produce cyclic compound in the presence of an acid or electrophile.The reaction of carbon-carbon triple bond of alkynones and nucleophile would be conducted in the presence of an acid or electrophile.According to the difference of nucleophiles,carbon nucleophiles(electron-rich aromatics and olefins)and heteroatom-containing nucleophiles(oxygen,sulfur,and nitrogen)involved cascade cyclization reactions were introduced.Chapter FiveIn the fifth chapter,Br?nsted acid catalyzed synthesis of 4-pyrones and NIS-promoted selective synthesis of 4-pyridones and 3-pyrrolidones from the same diynone substrates were developed.The molecular structures of these three products could be the key skeletons of some natural product molecules with pharmacological activities.Chapters Six2H-chromene and 4-chromanone are important flavonoid skeletal structures,whose synthetic methods have always been widespread concern for organic chemists.In the sixth chapter,two cyclization forms of the same propynol substrate in two reaction systems were developed,for the constructions of 2H-chromene or 4-chromanone skeleton structure,respectively.The resulting iodosubstituted 4-chromanone products can also be further derived by palladium-catalyzed cross-coupling reactions.