Palladium/Copper-Catalyzed Aromatic And Olefinic C(sp~2)-H Functionalization

Owing to the ubiquity of C-H bonds in organic molecules,direct cleavage of C-H bonds and conversion them into desired functional groups can not only shorten the synthesis path but also save reagents and solvents,which leads to a high atom economy without any chemical wastes being generated during the reaction process,currently,the most general methods in C-H bond activation and functionalization rely on transition metal catalysis.The current thesis focuses specifically on palladium and copper-catalyzed aromatic and olefinic C（sp²）-H bond functionalization.The organization of the research content is on the basis of the gradual and in-depth study of three types of C（sp²）-H bond being functionalized:remote aromatic C（sp²）-H bond,ortho aromatic C（sp²）-H bond,and ortho olefinic C（sp²）-H bond.A copper-catalyzed direct remote aromatic C（sp²）-H bond functionalization has been successfully developed.This catalytic amination process utilizes Cu（OAc）₂ as a catalyst with N-fluorobenzenesulfonimide as the amination reagent and the oxidant for direct remote aromatic C（sp²）-H bond C5-amidation of 8-amidoquinolines to form C-N bond under 80℃.This method is carried out with no extra ligands and additives being costly used leading to 22 examples in up to 95%yield.Afterward,the formation of C-O bonds via remote aromatic C（sp²）-H bond functionalization at C4 position of aryl oxazolines has been described.This reaction is performed using copper trifluoromethanesulfonate as a catalyst with hypervalent iodine complexes being used as the oxidant to form aryl oxazolines derivative in 97%yield under 80℃through an ion pair between trifluoromethanesulfonic acid and pyridine.Methods for palladium and copper-catalyzed direct ortho aromatic C（sp²）-H bond functionalization have been described.In this thesis,we describe a method for direct ortho aromatic C（sp²）-H bond functionalization to form intramolecular C-N bond,which is performed using Pd（OAc）₂ with tert-butyl peroxybenzoate（TBPB）as the oxidant and directed by a protected amino group under 40℃.This mild method performs well in tetrahydrofuran to form25 examples of N-substituted carbazole derivatives in up to 99%yield,including 3 examples of late-stage functionalization for derivatives containing medicine molecules.When using H₂O as the solvent,24 examples of N-substituted carbazole derivatives in up to 81%yield were obtained.Based on the radical inhibition tests and the detailed studies of kinetic isotope effect（KIE）,we preliminary propose that the process is carried out through a Pd（II）/Pd（IV）catalytic system.Meanwhile,the Pd（II）is oxidized to Pd（IV）by perester via a synergistic mechanism without single-electrons or free radicals under a lower temperature.Worthy to be considered,the process utilizes perester as the oxidant avoiding toxic byproducts and potential side reactions compared with hypervalent iodine complexes being costly used,which implied the advantages of the catalytic mode involving perester with transition metal catalyst in the activation and functionalization of C-H bonds.Moreover,we also developed a method for synthesis of N-substituted carbazoles derivative which uses Cu（OAc）₂ as a catalyst and bis（tert-butyl）peroxide as an oxidant in 75%yields under 100°C.A palladium-catalyzed direct ortho olefinic C（sp²）-H bond functionalization has been successfully developed.With the in-depth study of the strategy mentioned above for the combined use of perester and in the C-H activation,we describe a Pd（OAc）₂-catalyzed ortho olefinic C（sp²）-H bonds benzoxylation of benzofurans at C3 position.Which is carried out using perester as both the benzoxylate reagent and the oxidant and directed by a protected amino group.When mesitylene is used as solvent,23 examples of benzofuran derivatives are obtained under room temperature in up to 98%yield.And the transformation performs well with up to 89%yield in water giving 14 examples of benzofuran derivatives at 60°C.Control experiments suggesting that the reaction is proceeded under Pd（II）/Pd（IV）catalysis with coordination of perester to Pd（II）.This work is not only a powerful complement to the strategy proposed in this thesis for the combined use of transition metals and peresters,but also an important extension of this strategy to olefinic C（sp²）-H bond functionalization.There are no excess carboxylic acids and hypervalent iodine complexes s being costly used in the process compared with the traditional methods.In conclusion,a gradual and in-depth investigation of the C-H functionalization including remote aromatic C（sp²）-H bond,ortho aromatic C（sp²）-H bond,and ortho olefinic C（sp²）-H bond to construct C-N bonds or C-O bonds has been developed.Moreover,we propose a catalytic mode involving perester with Pd（II）catalyst in the activation of inert C-H bonds which could perform in lower tempreture.In the meanwhile,the mechanism of this method in the C（sp²）-H bond functionalization is also investigated.The content of this thesis is the further exploration and efficient application of palladium and copper catalyzed C（sp²）-H bond functionalization.