Study On The Dimerization And Phosphonation Of Heteroaryl N-Oxides Under Metal-Free Conditions

In this thesis, direct dimerization and phosphonation of heteroaromatic N-oxidesunder metal-free conditions are studied. The main results obtained are shown asbelows:1. Dimerization of heteroaromatic N-Oxides under metal-free conditionsBiheteroarematic N-oxides are an important class of compounds, which are usedas chelating ligands in the field of organic synthesis. Conventional methods to buildsuch structure typically involve multistep cryogenic reactions, ortransition-metal-catalyzed Het-X/Het-M coupling reactions. There are problems withthese procedures, such as the harsh reaction conditions, and usage of noble metals,which have limited the applications in laboratory and industry. Herein, we havedeveloped an efficient approach to synthesize biheteroarematic N-oxides compoundsunder metal-free conditions (Scheme1). The optimum reaction conditions aredetermined as follows: in toluene at120oC for3hours by usingtBuOLi (1.5equiv)as the base. This new methodology has been demonstrated to be suitable for thehomocoupling of a broad range of substrates, which affords a broad range of2,2’-biheteroaromatic mono N-oxides in up to93%yields. The result of controlledexperimental results indicated that the dimerization was achieved via a nucleophilicaddition-elimination process (Scheme2). 2. Direct phosphonation of heteroaromatic compounds under metal-and externaloxidant-free conditionsAryl and heteroaryl phosphonates have wide application in many fields, such asmaterial sciences, pharmaceuticals, agricultural chemicals and organic synthesis asligand. They can be achieved through two major mechanisms, including directmetalation and radical process. However, some challenges exist with these proceduresdue to the strong coordinating character of phosphorus reagents with metal center andpotential contamination of the products from the high loading of metal, andrequirement of stoichiometric oxidants. Recently, the contribution of Hartwig, Yu,Glorious, You, Fagnou and our group have disclosed that N-O group could be servedas both directing group, and internal oxidant for the metal-catalyzed dehydrogenativecoupling reaction under external oxidant free conditions.To verify our hypothesis, the condensation of quinoline N-oxide1a withdimethyl H-phosphonate2a was initially chosen as a model reaction to screen thevarious reaction parameters. Finally, the optimal reaction conditions for the directregioselective phosphonation of quinoline N-oxide were identified to be toluene asthe solvent at100oC for20hours (Scheme3). Under the standard reaction conditions,a wide variety of heteroaryl phosphonates were afforded in up to92%yields inchemo-and regioselective manners under external oxidant and metal free conditions. This procedure features with practicality, high efficiency, environmental friendlinessand atomic economy. We deduced that quinoline N-oxides might serve as an internaloxidant for radical initiator to form C-P bond via radical mechanism (Scheme4).