Pd-catalyzed C-P Coupling Of Heteroaryl Boronic Acid With H-phosphonate Diesters And Studies On The Synthesis Of Imidazopyridines

In this thesis, the first methodology to construct C-P bond has been performed by using coupling reactions of heteroaryl boronic acid with H-phosphonate diesters under Pd-Ag catalyzed system, which offered a variety of useful heteroaryl phosphonates with moderate to good yields via deboronation reactions. 1. A series of substituted pyridine boronic acids were prepared (Scheme 1) from corresponding substituted pyridine halides under the effects of butyllithium and triisopropyl borate to furnish the starting materials for the reactions of H-phosphonate diesters with different heteroaryl boronic acid.2. The model reaction of 3-pyridinylboronic acid and (tPrO)2P(O)H was studied by controlling the ratio of the reactants, various catalysts, different additives, solvent, ligand, reaction temperature and reaction time. The study manifested that the reaction catalytsis system with 0.15 equiv. PdCl2 as the catalyst,2 equiv. Ag2O as additive,2 equiv. PPh3 as ligand,3 ml DMA as solvent,100 ℃ for 2 h was best condition for this reaction (Scheme 2).3. With the optimized conditions, various substrates were surveyed to explore the scope and limitations of the reaction. The results showed that a variety of 3-substituted pyridinylboronic acid derivatives and other heteroaryl boronic acids could give the desired products in moderate to good yields. The study showed that N, N-dimethylamino, propoxy, trifluoromethyl, phenyl and halide were all well tolerated in the above-mentioned conditions. What’s more, such model reaction also applied to arylboronic acids. This method could reduce the reaction time effectively compared with previous reports.4. With cheap and commercial available 2-aminopyridine compounds as raw materials, we synthesized three kinds of imidazo[1,2-a]pyridine through the reaction with two steps(Scheme 3).