Development of metal-free based one-pot synthetic protocol for the facile constructions of indole and coumarin based fused heterocycles

Abstract

This thesis presents research into the development of metal-free based green synthetic methods for the direct access to tetrahydrothiopyrano[2,3- b]indoles, furo/pyrano[3,2-c]chromen-2-ones and their related heterocyclic scaffolds in a stereoselective manner. We believe that current catalytic/noncatalytic processes will offer new synthetic techniques towards the efficient syntheses of interesting functionalized indole and coumarin derivatives. Moreover, there is a highly scope for more useful chemistry to be originated from this area. To begin with a general introduction for the syntheses and applications of indole and coumarin heterocycles, with historical perspectives and synthetic methodologies developed for the preparations of annulated indole/coumarin scaffolds through various efficient organic transformations have been discussed in the first chapter.The next chapter describes an efficient one-pot three component method for the synthesis of biologically attractive 2,3,4-trisubstituted-2,3,4,9- tetrahydrothiopyrano[2,3-b]indole derivatives in good to excellent yields with moderate diastereoselectivities using organocatalysis. Furthermore, the enantioselective synthesis of title compounds was achieved by this methodology.In the third chapter, one-pot synthesis of 2,9-dihydrothiopyrano[2,3-b]indole scaffolds showing large Stokes Shifts has been reported. This chapter unfolds a mild, convenient, practical and general one-pot high yielding method for the synthesis of N-Boc-2-aryl-3-nitro-2,9-dihydrothiopyrano[2,3- b]indole scaffolds via a tandem aromatic nucleophilic thiolation/thio- Michael/Henry reaction of N-Boc-2-chloro-3-formylindoles, NaSH·H2O with aryl-substituted nitroolefins in CH2Cl2 at room temperature, followedby in situ dehydration of resultant tetrahydrothiopyranoindole in the presence of activated molecular sieves.The fourth chapter demonstrates a remarkable solvent effect on the reaction of 4-hydroxycoumarin with (E)-3-aryl-2-nitroprop-2-enol: Facile synthesis of highly substituted furo/pyrano[3,2-c]chromenes. This chapter describes a mild, simple, convenient, high yielding procedure for the construction of 2- (hydroxymethyl)-3-aryl-4H-furo[3,2-c]chromen-4-one scaffolds via a onepot reaction of substituted 4-hydroxycoumarins with (E)-3-aryl-2-nitroprop- 2-enols in water without using any catalyst in 5-6 hours.Chapter five describes a catalyst-free facile synthesis of 4-sulfanylcoumarins involving 4-mercaptocoumarin and (E)-3-aryl/hetero-aryl-substituted-2- nitroprop-2-enols/MBH acetates of nitroolefins. Here, the nucleophillic substitution reaction between 4-mercaptocoumarin and several (E)-3- aryl/hetero-aryl-substituted-2-nitroprop-2-enols/MBH acetates of nitroolefins in DMSO and MeOH respectively at 70 °C under catalyst-free conditions is reported. This operationally simple method delivers mediocre to good yields of a series of novel functionalized α-(4-thiocoumarinyl)-􀈕- nitrostyrenes and (E)-dithiocoumarinyl styrene derivatives with excellent stereoselective manner.The final chapter of this thesis focuses on the conclusion and future outcomes of the current synthetic methodologies accomplished during the entire series of works.