Studies On The Construction Of Novel Nitrogen Heterocycles By Hydrogen Transfer/Cyclization And Cycloaddition Strategies

Nitrogen containing heterocycles with diversified structures and various functions have found wide applications in organic chemistry,pharmaceutical chemistry,agrochemical development,and materials science.Thus,in the past decades,chemists have developed a series of synthetic methodologies to construct nitrogen heterocycles with different functional groups,and applied them to the total synthesis of alkaloids and drug development.Among them,synthetic organic reactions based on intramolecular hydrogen transfer/cyclization and cycloaddition strategies have attracted much attention due to their outstanding atom economy and concise nature.Nevertheless,there are still obvious limitations of the substrate type of these two methodologies.Therefore,the development of new types of substrates to construct novel nitrogen heterocyclic systems possesses distinct academic significance and potential applications.In line with the above objectives,a series of new methods of constructing novel nitrogen heterocyclic structures have been developed in this dissertation with the following research findings:(1)The new method of constructing trifluoromethylated tetrahydroquinazolines has been developed.With trifluoroethylamine hydrochloride and o-amino-benzoyl species as starting materials,N-trifluoroethyl tetrahydroquinazoline derivatives were accessed via a condensation/hydride transfer/cyclization sequence.This reaction gave the desired products in high yields with excellent diastereoselectivities with an easy operating prosess and without extra catalyst(up to 99%yield,>20:1 dr).(2)The new method of constructing 4-phenylsulfonimide benzo[e]indolizidines has been developed.With 3-(2-(alkylamino)styryl)benzo[d]isothiazole 1,1-dioxide and 4-(2-(alkylamino)styryl)benzo[e][1.2,3]oxathiazine 2,2-dioxide as the substrates,4-sulfimide-benzo[e]indolizidines derivatives were synthesized in the presence of trifluoromethanesulfonic acid as the catalyst via a hydride transfer/cyclization cascade.This easily operating reaction gave 4-sulfimidebenzo[e]indolizidine derivatives in high yields with excellent diastereoselectivities(up to 96%yield,>20:1 dr).(3)The method of constructing indolinine-modified spirooxindole-pyrrolidines has been improved with isatin as the requisite azomethine ylide precursor.The indolinine-modified spiro-oxindole derivatives were constructed in high yields with excellent regioselectivities via three-component[3+2]cycloaddition involving N-benzyl isatins,benzylamines and 2-alkenylindolenines(up to 91%yield.14:1 rr).(4)The new method of constructing novel complex benzo[b]indolizidine scaffold has been developed.Benzo[b]indolizidine structure containing five contiguous stereogenic centers was constructed via sequential[4+2]/[2+2]cycloadditions involving 2-alkenylindolenines.This reaction has advantages of mild condition,high yields,and excellent diastereoselectivities(up to 85%yield,>20:1 dr).