Catalytic Activation And Transformation Of C-F, C-N, C-S And C-H Bonds

This thesis focuses on investigation of cleavage and recombination of C-F, C-N, C-S and C-H bonds. We explored the methodologies and construction of new C-C、 C-N and C-O bonds through the catalytic activation of unreactive C-F, C-N, C-S and C-H bonds in the presence or absence of transition metal.Chapter1presents the Kumada cross-coupling reaction of aryl fluorides with aryl Grignard reagents catalyzed by nickel complexes. Among the complexes tested, nickel complexes22b and22c showed excellent catalytic activity for the cross-coupling reactions of activated, unactivated and deactivated aryl fluorides with aryl Grignard reagents at room temperature. The reaction can tolerate functional groups such as CH2OH and CONEt2groups as well as pyridyl ring.Chapter2deals with the cross-coupling reaction of aryl fluorides with organozinc reagents using Ni(PCy3)2Cl2as the catalyst. Activated, unactivated and deactivated aryl fluorides can be efficiently coupled. Electron-rich and electron-poor arylzinc reagents and p-hydrogen free alkylzinc reagents such as benzylzinc chloride and methylzinc chloride were proven to be suitable nucleophiles. Pyridyl ring and a series of functional groups involving NMe2, OMe, COOEt, C(O)NEt2, PhC(O), and imino groups were tolerated. In addition, we also confirmed that the PhC(O) group is an effective directing group for the selective activation of C-F bonds to form o-arylated or o-alkylated products.Chapter3describes an effective catalyst system consisted of Ni(COD)2and IPr-HCl which catalyzes the coupling of fluoroarenes with amines in the presence of tBuONa. The catalyst is highly efficient for the reaction of cyclic amines with activated, unactivated and deactivated fluoroarenes. Acyclic amines are also effective nucleophiles for the amination of activated aryl fluorides. The reactions can tolerate functional groups including PhC(O), C(O)NEt2, CF3, OMe and vinyl group as well as nitrogen-containing heterocycles. This methodology provides a valuable complement to the traditional SNAr substitutions of aryl fluorides, and broadens the scope of aryl electrophiles in the Buchwald-Hartwig amination.Chapter4is on a Pd(π-allyl)Cl]2/PCy3or Pd(π-allyl)Cl]2/IPr-HCl-catalyzed direct C-H arylation of azoles and thiozaoles with aryltrimethylammonium salts via C-H/C-N activation. The method displays a broad substrate scope. Various aryltrimethylammonium salts including electron-rich and-poor ones can be used as arylating reagents. The reaction gives good to excellent yields in most cases and can tolerate various functional groups such as OMe, CF3, C(O)NEt2, PhC(O), CN groups as well as pyridyl ring.Chapter5presents a Pd(π-allyl)Cl]2/dcype-catalyzed direct C-H arylation of azoles and thiozaoles with aryl thioethers via C-H/C-S activation. The method displays a broad substrate scope. Various aryl methyl sulfides and diaryl sulfides including electron-rich and-poor ones as arylating reagents can be coupled. The reaction gives good to excellent yields in most cases and can tolerate various functional groups such as OMe, CF3, C(O)NEt2, PhC(O) and CN groups as well as pyridyl ring.Chapter6presents a NiCl2(dppp)-catalyzed Caryl-Csp3cross-coupling reaction of aryl methyl sulfides and alkyl lithium reagents. Various arylmethyl sulfides including activated, non-activated and deactivated arylmethyl sulfides as arylating reagents can be coupled. Premary and secondary alkyl lithium reagent proved to be good nucleophiles. Highly active alkyl lithium reagent TMSCH2Li reacted with activated or non-activated arylmethyl sulfides required only Ni(COD)2as catalyst and moderate to excellent yields were achieved.Chapter7presents a Bu4NI-catalyzed reaction of aldehydes with ethers or ketones using TBHP as the oxidant. A series of aldehydes including aromatic/heteroaromatic aldehydes and functionalized aldehydes were employed. Cyclic and acyclic diethers as well as propiophenones are suitable coupling partners. A crown ether,1,4,7,10-tetraoxacyclododecane, was also tested for the oxidative coupling.2-Arylacetaldehydes were demonstrated to react with diethers, but unexpectedly resulted in aromatic acyloxy ethers. All reactions are metal-free and employed environmentally benign oxidants and commercially available materials. This is a simple and straightforward methodology for the synthesis of a-acyloxy ethers and a-acyloxy ketones.