Copper-Mediated Direct Aryloxylation Of Benzamides Assisted By An N,O-bidentate Directing Group

In this thesis, we have developed a method of cooper-mediated selective mono-or diaryloxylation of benzoic acid derivatives by using2-aminopyridine1-oxide as a removable N,O-bidentate directing group. The method shows high generality and good functional group tolerance, providing a straightforward way for the synthesis of mono-or diaryloxylation benzoic acids. The main results are shown as follows:1. Synthesis and characterization of benzamidopyridine1-oxidesA wide of benzamidopyridine1-oxides1were synthesized using benzoic acid derivatives and2-aminopyridine1-oxide, which was easily synthesized from2-aminopyridine (Scheme1). The new compounds were characterized by1H NMR,13C NMR,19F NMR and HRMS. Scheme12. Cu(II)-mediated monoaryloxylation of benzoic acid derivatives The optimal conditions are obtained by screening the reaction conditions, including temperature, base, additive and solvent. The reaction employs1eq. Cu(OAc)2, air as an oxidant, phenols as coupling partners, o-xylene as solvent,4-dimethylaminopyridine as additive and cesium carbonate as base at130oC, affording the corresponding monoaryloxylation of benzoic acid derivatives3(Scheme2). The new compounds were characterized by1H NMR,13C NMR,19F NMR and HRMS. Scheme2 3. Cu(II)-Mediated diaryloxylation of benzoic acid derivatives The optimal conditions are determined by screening the reaction conditions, including temperature, base, additive and solvent. The reaction empolys2eq. Cu(OAc)2, air as an oxidant, phenols as coupling partners, pyridine as solvent,4-dimethylaminopyridine as additive and cesium carbonate as base at130oC, affording the corresponding diaryloxylation of benzoic acid derivatives4(Scheme3). The new compounds were characterized by1H NMR,13C NMR,19F NMR and HRMS.Scheme34. The synthesis of nonsymmetry biaryl ether and removal of directing group Nonsymmetry biaryl ether6was synthesized using2-(2-phenoxybenzamido) pyridine1-oxide (3aa) and4-iodophenol (2f) as starting material (Scheme4) in98%yield. The reaction not only can synthesize nonsymmetry biaryl ethers, but also the directing group can be successfully removed by ethanolysis affording the corresponding compounds5and7. The compound5is known, which wascharacterized by1H NMR and13C NMR. The new compounds6and7were characterized by1H NMR,13C NMR and HRMS. Scheme4...