Study On Stereoselective Synthesis Of Polycyclic Benzosultams

Polycyclic benzosultams which is the basic skeleton of many drug molecules exhibit a wide range of important biological activities,especially the compounds with chiral centers.Due to the biological importance,the stereoselective synthesis of these compounds has attracted broad attentions from organic and medicinal chemists.In this thesis,we have developed novel cyclic N-sulfonylimine-based organic tandem reactions and cycloaddition reactions for the diastereo-and enantioselective synthesis of structurally complex polycyclic benzosultams.It has enriched the organic synthesis of polycyclic benzosultams,and provided new ideas and methods for the synthesis of the compounds with potential biological activity.In the first part,we systematically explored the three-component organic tandem reaction of pyridines,alkynoates and cyclic N-sulfonylimines.Using the model reaction,we optimized the reaction conditions in terms of solvents,additives,substrate ratios and temperatures.And then,with the optimal reaction conditions,we extended the reaction scope of the tandem reaction by applying structurally different substrates.The tandem reactions furnished desired products in high chemical yields(up to 98%)with excellent diastereoselectivities(up to >20:1).Lastly,we unambiguously determined the relative configuration of these target molecules by X-ray single crystal structure analysis.Moreover,we proposed the reaction mechanism for tandem reaction of pyridines,alkynoates and cyclic N-sulfonylimines.In the second part,we have disclosed the organocatalytic [3+2] cycloaddition reaction between 3-isothiocyanate oxindoles and cyclic N-sulfonylimines.With the use of the model reaction,we screened organocatalysts,solvents,acids,bases,additives and catalyst loading as well to optimize the reaction conditions.Under the optimized reaction conditions,we extended the reaction scope of the organocatalytic[3+2] cycloaddition reaction by choosing structurally varying substrates.It has been indicated that the [3+2] cycloaddition reaction enabled the formation of title molecules in excellent diastereoselectivities(up to >20:1),moderate chemical yields(up to 64%)and good stereoselectivities(up to 88%).