Synthesis Of Trifluoromethylated Cyclopentenedines, Fulvenes And Aryl Thiol Ethers Based On Pre-and Post-functionalization Strategy

Fluorine is the13th most abundant element in the earth's crust, where it occurspredominantly in the form of cryolite (Na3AlF6), fluorite (CaF2) and fluorapatite[Ca10(PO4)6F2]. In spite of this, there are only a very few nature organic molecules bearing aC F bond as most terrestrial F are bound in insoluble form and their poor nucleophilicityunder natural conditions, which hinders uptake by aqueous biological systems. However,fluorinated functional groups can remarkably enhance the lipophilicity, membranepermeability, elevate electronegativity and oxidation resistance of fluorine containing organiccompounds. Therefore, approximately20-30%of modern pharmaceuticals and agrochemicalscontain fluorine.In the recent30years, these advantages have stimulated an enormous amount of strategiesdirected to the synthesis of fluorinated compounds, especially the developments oftrifluoromethylation reactions as evidenced by over900publications in the year of2013.These references reported the introduction of trifluoromethyl group (CF3) into variousstructures by using diverse trifluoromethylated agents to construct trifluoromethylatedderivatives via nucleophilic, electrophilic and radical trifluoromethylations.Based on the extensively researched1,2-addition reaction of versatile reagent TMSCF3(trifluoromethyltrimethylsilane, Ruppert–Prakash reagent) with divinyl ketones or p-quinones,the study of this thesis fouses on the discovery of new strategies of the syntheses of severalnovel carboncycles including highly functionalized CF3-bearing cyclopentadiens, fulvenes,and aryl thiol-ethers by one-pot reactions and tandem reactions, respectively, starting from theeasily available3-CF3-1,4-dien-3-ols and4-CF3-p-quinol derivatives. We chose startingmaterials which could be introduced trifluoromethyl moiety into carbon fraworks such asp-quinones (“pre-functionalization” strategy) followed by introducing different functionalgroups regioselectively (“post-functionalization” strategy). This thesis combines experimentalresults and related reaction mechanisms to discuss the synthesis of trifluoromethylatedcyclopentenedines, fulvenes and aryl thiol ethers based on pre-and post-functionalizationstrategy in depth.The thesis is divided into five chapters. Reviewing the research on the use of TMSCF3and trifluoromethylation reactions in recent years is in the first chapter, and the thesisproposal is presented in chapter two.In chapter three, the preparation of the1,2-adducts of divinyl ketones, p-quinones basedon the1,2-addition reactions of TMSCF3is described.Chapter four describes a novel “one-pot” reaction to give CF3-bearing cyclopentadiens and fulvenes via Nazarov Reaction or under Vilsmeier conditions, respectively. Thismetal-free reaction is a noteworthy effective method.In Chapter five, a new strategy is discussed comprehensively. Themeta-double-functionalization/aromatization strategy based on the reaction of4-CF3-p-quinols and ?-EWG ketene dithioacetals promoted by Lewis acid under mildcondition for the synthesis of functionalized trifluoromethylated aryl thiol ethers. Thisregiospecific manner has been developed that enables the introduction of two differentfunctional groups onto an “aromatic ring” in the ortho-and para-position to a strongelectron-withdrawing CF3group in a single step with high to excellent yields.