Copper-mediated Synthesis Of Fluoroalkyl (Thio) Ethers And Trifluoromethylated Aryl Sulfones

The incorporation of fluorine or fluorine-containing group into organic compounds can often remarkably enhance the lipophilicity,bioavailability and metabolic stability of the parent molecules.As a result,fluorine-containing compounds have been widely used in pharmaceuticals and agrochemicals,as well as in materials and life sciences.Until now,the development of new methods for introducing various fluorine or fluorine-containing groups into organic molecules has been received a great attention.In this thesis,the research work was focused on the introduction of heteroatom-based fluoroalkyl groups.A series of fluoroalkyl?thio?ethers and trifluoromethylated aryl sulfones were prepared via these new methods,which were divided into 4 parts:Part ?: The copper-mediated oxidative trifluoromethylthiolation of unactivated terminal alkenes using AgSCF₃ has been developed.In the presence of AgSCF₃ as the SCF₃ source,Cu?OAc?₂ as the copper salt and K₂S₂O₈ as the oxidant,the terminal alkenes were allowed to react in DMSO at 60 ? for 6 h,the corresponding trifluoromethylthiolated allylic compounds were obtained in 46-76% yields.This mild reaction condition allowed the tolerance of a wide range of functional groups.Part ?: A tunable chemoselectivetrifluoromethanesulfonylation and trifluoromethylation of arenediazonium tetrafluoroborates with Langlois reagent?NaSO₂CF₃?has been developed.Different products were obtained under different conditions from the same substrates and NaSO₂CF₃.In the presence of catalytic amount of Cu2 O,the arenediazonium tetrafluoroborates and NaSO₂CF₃ were allowed to react in DMSO at room temperature for overnight,affording the corresponding aryl trifluoromethanesulfones in 45-90% yields.However,in the presence of oxidant t-butyl hydroperoxide,Cu?MeCN?₄BF₄,2,2':6',2''-Terpyridine?Tpy?,and Me CN/H2O?20/1?,the arenediazonium tetrafluoroborates transformed into trifluoromethylated arenes in 30-63% yields at 45 ?.Both of these transformations proceed under mild conditions and tolerated many functional groups.Part ?: A copper-promoted Ritter-type trifluoroethylation of arenediazonium tetrafluoroborates has been developed.In the presence of catalytic amount of Cu?MeCN?₄BF₄ as the copper salt,KF as initiator,Me CN as the solvent,the reaction of arenediazonium tetrafluoroborates with TMSOCH2CF3 at 70 ? for 6 h afforded the corresponding trifluoroethylated imide derivatives in 30-85% yields.Part ?: A mild and efficient copper-catalyzed oxidative trifluoroethoxylation of aryl and heteroaryl boronic acids using CF₃CH₂ OH has been developed.In the presence of catalytic amount of Cu?OAc?₂ as the copper salt,pyridine as the ligand,air as the oxidant Na₂CO₃ as the as the additive and 1,2-dichloroethane as the solvent,the reaction of aryl and heteroaryl boronic acids with CF₃CH₂ OH at room temperature for 14 h afforded the corresponding aryl and heteroaryl trifluoroethyl ether in 35-81% yields.This mild reaction conditions allowed the tolerance of a wide range of functional groups.This mild process was also applied to the late-stage trifluoroethoxylation of a medicinally relevant coumpound.