Exploration And Application Of Synthesis Of Heterocycles Through Metal-free Coupling Reactions

Recently,transition-metal-free-catalyzed coupling reactions have been well studied since they were efficient and direct strategies for C-C bond or C-X bond formation,further more transition-metal-free-catalyzed coupling reactions as a major topic in organic chemistry,have made significant progress and received more and more attention.Along with the conceptions of high atom economy and green chemistry which insisted by our group from the very beginning,we have got a little bit achievements on the synthesis of heterocycles through metal-free coupling reactions.The main contents and results are listed as following:(1)The intermolecular cascade cyclization promoted by TEA/DMF systemThis procedure involved C-C and C-N bonds formation in one-pot.We have developed a new base-promoted intermolecular cascade cyclization reaction of substituted 3-aryl(heteroaryl)-3-chloroacrylaldehydes and tetrahydroisoquinolines in one-pot.The reaction provides a facile and practical synthesis of pyrrolo[2,1-a]isoquinolines.A number of pyrrolo[2,1-a]isoquinolines were synthesized in moderate to high yields(up to 97%).In addition,mechanistic studies indicated that this process did not involve a radical pathway,and based on all experimental observations,we thought this coupling reaction could finish by an imine intermediate.(2)The intermolecular cascade cyclization promoted by TBAC/TBHP systemThis procedure involved double C-C bonds formation in one-pot.That was our first time to use a possible radical pathway to construct phenanthridine-6-carboxamides,under K2HPO4 circumstance,the one-pot strategy can be applied to a number of 2-isocyanobiphenyls and DMF with good functional group tolerance,the yield up to 86%.This work may not perfect,but we have accumulated a lot of work experience from this work.(3)The intermolecular cascade cyclization promoted by TBAB/TBHP systemThis procedure involved C-C and C-S bonds formation in one-pot.A metal-free pathway for constructing 6-aryl(alkyl)thiophenanthridines through oxidative cascade cyclization of isocyanides with thiols is developed.This pathway is characterized by SH bond cleavage of commercially available thiols,and subsequent C-S/C-C bond formation,which is suitable for a wide scope of substrates and by which a variety of 6-aryl(alkyl)thiophenanthridines could be synthesized in good to excellent yields(up to 86%).Besides,based on all experimental observations,a plausible reaction mechanism is proposed.(4)The intermolecular cascade cyclization promoted by NH4I/TBHP systemThis procedure involved C-C and C-N bonds formation in one-pot.Different from part(1),we hope this reaction could through a radical pathway.After last two parts work,we attended to synthesize 6-aminophenanthridines from 2-isocyanobiphenyls and N-source via a radical way.After screening works,we used saccharin as radical precursor,catalyzed by NH4 I with TBHP as an oxidant,we could get the target product in 46% yield,but this result was dissatisfactory,further work is being carried out in our lab.