Studies On The Synthesis Of Heterocycles From Diazopyruvates

Heterocyclic Compounds are widely found in nature and because of their extensive application particularly in pharmaceutical,it made great attention among scientific community to develop new methodologies for the synthesis of heterocyclic compounds.In this context,reactions involving diazo compounds is powerful tool for the construction of various biological significance heterocyclic compounds.A variety of methods have been developed for the synthesis of heterocyclic compounds by transition metal-catalyzed reactions involving carbene,particularly multicomponent reactions provide straightforward path to build diverse structural and complex skeleton in highly stereoselective manner.This strategy involves onium ylides or zwitterionic intermediates trapping with electrophiles.In these reactions,a “delayed proton transfer” that occurs after the trapping process produces novel multicomponent products.As part of our research interest in this area,we established various kind of heterocyclic compounds through multicomponent reaction by using different types of diazo compounds as carbene source.This dissertation present unprecedented route for the construction of heterocyclic compounds by using diazopyruvates with amine substrates unlike previously reported ammonium ylides trapping with electrophiles.As compared with our previous work,we have been introduced different diazo compound with an additional carbonyl functionality for further synthetic elaboration.The strategy provides rapid construction of highly biological active heterocyclic compounds from readily available starting materials under mild conditions.In Chapter 2,an unprecedented diversity-oriented synthesis of multisubstituted pyrrolidine and indole from anilines and diazopyruvates is presented.In the presence of ruthenium catalyst,N-H insertion of aniline with ruthenium carbene lead to the formation of enol intermediate which underwent oxidation to generate imine ester intermediate as potential coupling partner.The enol key intermediate exist as trimeric form via hydrogen bonding confirmed by X-ray analysis.The reaction leads to the formation of five new bonds with four contiguous stereocenters pyrrolidine in highly diastereoselective manner.The gram scale reaction also gave good yield of pyrrolidine with high diastereoselectivity.The strategy also provide an access towards highly substituted pyrroles.By using iron chloride(III)as co-catalyst,the reaction do not end up with pyrrolidine product but undergo fragmentation of pyrrolidine and gave indole as final product.The developed strategy provides diversity-oriented synthesis of pyrrolidine and indole under mild conditions from readily available aniline and diazopyruvates.In order to determine the biological significance of the synthesized pyrrolidine and indole compounds,products were subjected for the in vitro anticancer activity using CCK-8 assay.Various compounds of pyrrolidine and indole showed good inhibition activity against HCT116 cell.In Chapter 3,the cascade synthesis of substituted 1,4-oxazine from readily accessible starting materials ?-amino carbonyl compounds and diazopyruvates in the presence of ruthenium chloride under mild conditions is presented.This strategy involves selective enol intermediate transformation in to highly biological significant heterocycle 1,4-oxazine skeleton.The reaction proceeded through N-H insertion followed by intramolecular cyclisation.Our developed method give direct access to various kind of 1,4-oxazine.Numerous functional groups including aryl,aryl and alkyl substituents on ?-amino ketone gave good to excellent yields of 1,4-oxazines.