Development of domino technique for the synthesis of a novel class of indole derivatives and related scaffolds

Abstract

This thesis presents research into the domino technique for the synthesis of pharmaceutically important compounds such as substituted indoles, γ-carbolines, carbazoles and naphthalenes in an efficient manner. To begin with a general introduction to the syntheses and applications of substituted chromenylindoles, γ-carbolines, carbazoles, and naphthalenes with historical perspectives and synthetic methodologies developed for the construction of indole/hydrocarbon scaffolds through domino approach have been discussed in the first chapter.In the next chapter, a simple, convenient and one-pot method for the synthesis of a series of biologically promising 2-aryl/alkyl-substituted-3-(2-aryl/alkyl-4Hfuro[ 3,2-c]chromen-4-yl)-1H-indoles in good to high yields through a novel domino intramolecular hydroamination (C-N bond formation) of 2- alkynylanilines, followed by Friedel-Crafts alkylation/oxa-cyclization (creation of new C-C and C-O bonds) reaction between in situ generated 2-substituted indoles and several cyclic enynones using 2.0 mol% of AgSbF6 as a catalyst has been achieved.A catalyst-free, three-component domino protocol for the synthesis of functionalized γ-carboline derivatives involving several aryl/heteroaryl/alkyl/alkenyl/alkynyl/ferrocenyl/ aldehydes, 3-formyl indole derivatives and ammonium acetate as N-source in water at room temperature with broad substrate scope is illustrated in the third chapter .In the Fourth chapter, one-pot π-extension reaction of indole to carbazole on the surface of a basic alumina as an inexpensive reusable solid support by involving several 2-(3-formyl-1H-indol-2-yl)acetophenones/acetates and 2-aryl/heteroaryl/ alkyl-substituted nitroolefins (or in situ generated nitroolefins from aldehydes and nitromethane) under aerobic and solvent-free conditions has been developed.The fifth chapter demonstrates a simple, convenient and practical one-pot domino Michael-Henry-dehydration/aromatization reaction of 2-(2-formylaryl) acetophenones with trans-aryl/heteroaryl-substituted β-nitrostyrenes in EtOH at 75 ºC under air using DABCO (30.0 mol%) as an inexpensive organocatalyst for the synthesis of substituted naphthalenes. The final chapter of this thesis focuses on the conclusions and future outcomes of the current synthetic methodologies accomplished during the entire series of works.