Base-mediated regio-and stereoselective intermolecular hydroamination of alkynes

Abstract

The thesis is divided into four chapters: CHAPTER 1. Hydroamination: A general introduction CHAPTER 2. Base-mediated hydroamination of internal alkynes PART A. Addition of N-heterocycles onto Symmetrical Internal alkynes PART B. Addition of N-heterocycles onto Unsymmetrical Internal newlineAlkynes CHAPTER 3. Base-catalyzed hydroamination of terminal alkynes CHAPTER 4. Preferential addition of N-heterocycles onto halo-arylalkynes over N-arylation The chapter wise content is described briefly in the following pages: CHAPTER 1 : Hydroamination: A general introduction newlineHydroamination of alkenes, alkynes, and related unsaturated substrates represents an attractive strategy for the preparation of nitrogen heterocycles, enamines and imines. Enamines occupy a prominent place in organic synthesis, and variety of methods has been reported in the literature for their synthesis. Intermolecular addition of alkynes to primary and secondary amines have been well studied, however, addition of Nheterocycles on internal alkynes remain elusive. A notable work was reported by Knochel in 1999 for the addition of heterocyclic amines to phenylacetylene using CsOH.H2O in NMP (Scheme 1). Scheme 1. Later Kondo reported the addition of O- and N-nucleophiles to alkynes using newlinephosphazene base t-Bu-P4.7 Moreover, only one example of the addition of pyrrole on diphenylacetylene was reported using t-Bu-P4 with poor stereoselectivity (Scheme 2).7 Scheme 2. Phosphazene-catalyzed nucleophilic addition onto phenyl- or diphenylacetylene In this regard, stereo- and regioselective addition of N-heterocycles on alkynes is important and challenging. In our recent report on copper-catalyzed tandem synthesis of indolo- and pyrrolo[2,1-a]isoquinolines, the reaction was proposed to undergo via formation of a hydroaminated intermediate H (Scheme 3).8Scheme 3. Copper catalyzed tandem synthesis of indolo- and pyrrolo[2,1-a] isoquinolines With these successful reports on the synthesis of biologically important molecules via hydroamination and strong demand