Study On Ni(II)-catalyzed 1,2-cis-glycosidic Bond Construction

1,2-cis-glycosides are important and abundant classes of linkages and are commonly found as components in a variety of natural compounds.However,stereoselective construction of 1,2-cis-glycosides is challenging since the steric effect or neighboring group participation of the C-2 substituent on the sugar ring favor the formation of 1,2-trans glycosides.To date,various synthetic strategies of 1,2-cis-glycosides have been developed.However,there are some limitations in each method,such as:tedious synthesis of glycosyl donor,stoichiometric amounts activators and toxic reagents.In this thesis,we have reported a catalytic anomeric O-alkylation of 1,2-dihydroxyglycose with Ni(?)complexes,providing 1,2-cis-glycosides with high regioselectivity and stereoselectivity.In this thesis,the following main topics have been covered:1)Through the screening of a series of cheap,easily available and the strong coordination ability of transition-metal catalysts(such as Fe(?),Cu(?),Ni(?),Mn(?)),we found that Ni(acac)2 can achieve 1,2-cis-glycosides with high regioselectivity and stereoselectivity in glycosylation.2)Through the screening of a series of ligands,we found that acetylacetone ligands are very important to control the selectivity of glycosides.Therefore,it is suggested modulating steric and electronic factors of both catalysts enables activation of the axially oriented anomeric oxygens of glycosyl donor.3)Different kinds of substrates were explored under the optimal glycosylation condition.And the corresponding 1,2-cis-glycosides were obtained with good yields(73%-95%)and high selectivity,which proved that the method has a wide range of applications.4)To clarify the reaction mechanism of the catalytic anomeric O-alkylation using Ni(?)complexes,control experiments were carried out with 2-O-benzyl and 2-deoxy glucoses under the same conditions.In each case,mixed ?/?-glycosides(4da)and?-glycosides(4ea)were obtained in 17%and 15%respectively,and the starting materials were mostly recovered respectively in 63%and 82%.These results strongly demonstrated Ni(?)complexes can coordinate with the free hydroxyl groups at the 1,2-position of the glycosyl donor to form a cis-five-membered ring,which can realize the stereoselective construction of 1,2-cis-glucosides.