Research On Asymmetric Synthesis Of Pyridyl Alcohols And Their Nitrogen Oxides

The preparation of chiral secondary alcohols from prochiral ketones via asymmetric hydrogenation is an important transformation.In recent years,the Ir-f-amphox complex with tridentate ligand reported by Zhang group has shown excellent catalytic ability in asymmetric hydrogenation of ketones for high TON and enantioselectivity.The backbone of complex is ferrocene,which has air stability and wide application.It is difficult to study the asymmetric hydrogenation of pyridones for that pyridines can coordinate with the metal in the ligand during the hydrogenation reaction,which seriously affects the enantioselectivity and yield of the hydrogenation reaction.At the same time,the asymmetric hydrogenation product s of pyridyl ketones are important pharmaceutical intermediate skeletons,and the reduction products of other pyridones can also be used in the research of natural product total synthesis,bioactive molecules,and ligand synthesis.In this paper,the asymmetric hydrogenation of pyridone s and its nitrogen oxides is systematically studied.The complex of chira l tridentate phosphine nitrogen nitrogen ligand f-amphox with ferrocene as the skeleton and metal iridium is used as a catalyst.Selective hydrogenation reduction of this type of substrate is achieved with up to 99% ee and a high TON(The TON of 2-benzoylpyridine nitrogen oxide is up to 20 000)in a reaction system using isopropanol as the solvent and potassium carbonate or potassium hydroxide as the base.And the universalit y of the reaction substrate is good.In this paper,15 kinds of chiral pyridyl alcohols molecules and 11 kinds of chiral pyridyl alcohols nitrogen oxide molecules are synthesized by asymmetric hydrogenation method with high efficiency and high enantioselectivity.Part of the products can be used to synthesize carabaxamine,besilate and a new anti-cancer drug,so this method has a certain degree of industrial application value.