Application Of Iridium Catalyzed Hydrogenation In Diketone Desymmetrization

Asymmetric hydrogenation utilize molecular hydrogen and chiral catalysts to convert prochiral compounds,such as ketones,imines or olefins into chiral alcohols,amines and other reduction products.The method has a wide range of application in pharmaceuticals,agrochemicals pesticides,flavor and fragrence,natural product synthesis,natural product synthesis and functional materials.Asymmetric catalytic hydrogenation of ketone is one of the important methods to obtain chiral alcohols.Recently the complexes Ir/f-amphox,Ir/f-amphol and Ir/f-ampha developed by zhang xumu group achieved extremely excellent enantioselectivities and high TON in asymmetric hydrogenation of ketone.These ferrocene-based tridentate ligands are featured by good stability,easy synthesis,and wide applicability.?,?-disubstituted 1,3 cyclic diketones have high symmetry,so highly selective reduction of one of the carbonyl groups is a challenging task.Some approaches to the chiral hydroxy ketones have do been done,but the methods of asymmetric hydrogenation have not been reported yet.In the meanwhile,the reduction of a carbonyl group by the substrate to form chiral ring alcohols is also an important intermediate synthetic molecule,especially in the total synthesis of natural products and bioactive molecules.The chiral iridium complex,generated in situ from iridium and f-ampha catalyzes the asymmetric hydrogenation of highly symmetry cyclic ?,?-disubstituted 1,3-diketones in the presence of sodium tert-butoxide as a base in dichloromethane to give cyclic hydroxy ketones under mild conditions?25? and 40 atm H₂?.The asymmetric hydrogenation of the substrate,not only achieve the purpose of desymmetrization,also made excellent results?up to 95% yield,99% ee and 10000TON?,This method has the very good substrate universality.In this thesis,the aim of desymmetry is achieved by high efficiency,high yield and high enantioselectivity,and the target chiral alcohol molecule is obtained.This method was applied in the preparation of?+?- estrone.Modeling analysis revealed the origin of stereoselectivity in this chemical transformation.