Synthesis Of Novel Carbohydrate-based Chiral P, N Ligands And Their Applications In Cu-catalyzed Enantioselective1,4-conjugate Additions

In nature, Carbohydrate is very cheap, readily available and environmentally friendly, at the same time, it has research value as the chiral source, because of the sugar molecules have unique three-dimensional space structure and electronic characteristic, more and more chiral ligands derived from it and being used in various asymmetric catalytic reactions. In this thesis, it mainly studies with a new P、N ligands design, synthesis and application in Cu catalytic asymmetric1,4-conjugate addition reactions which take the glucose derivatives as chiral source. The thesis is divided into three parts.Chapter one:Systematic review of the development of asymmetric synthesis methods and the asymmetric synthesis methods are used in the synthesis of chiral drugs and natural products; Summed up with the subject in recent years by carbohydrate-derivatted ligands and they are applicated in asymmetric catalytic reactions, and proposed research objectives and research ideas.Chapter two:Combining with the Sub-groups effect, Hemilabile coordination effect ligands design concept taking amino glucosamine as chiral source, we synthetized two kinds of new P、N ligands which link with sugar ring structure. The new chiral ligands and intermediates have been confirmed through the1H NMR,13C NMR,31P NMR, MS or elemental analysis, etc. Different catalytic reactions were screened to study the ligands’catalytic activities and enantioselectivities at first.Chapter three:The new type of carbohydrate-based ligands was successfully employed in Cu-catalyzed asymmetric α,β-unsaturated ketone1,4-conjugate addition reaction has been studied. Systematic study of the variety factors which can affect the stereoselectivity (such as:solvent, temperature, catalyst precursor, the substance of molar ratio). The catalytic products were obtained in81%yield and achieved moderate enantioselectivities (ee78%), combining the experimental results and the theoretical analysis, a possible catalytic mechanism was proposed about the reaction.Through the exploration and research, we successfully designed, synthetized two kinds of carbohydrate-based P、N ligands, and they were successfully employed in Cu-catalyzed diethylzinc to α,β-unsaturated ketone asymmetric1,4-conjugate addition reaction too, the catalytic results proved that the new ligands have the catalytic activities and enantioselectivities.