Regioselective Preferential Nucleophilic Addition of <i>N</i>-Heterocycles onto Haloarylalkynes over <i>N</i>-Arylation of Aryl Halides

The study of preferential addition of heterocyclic amines onto halo-substituted arylalkynes over <i>N</i>-arylation under various catalytic conditions is described. The present work supports and confirms the mechanistic pathway of our recent work on the tandem synthesis of indolo- and pyrrolo-[2,1-<i>a</i>]isoquinolines via hydroamination followed by oxidative addition and not vice versa

Regioselective Preferential Nucleophilic Addition of <i>N</i>-Heterocycles onto Haloarylalkynes over <i>N</i>-Arylation of Aryl Halides

The study of preferential addition of heterocyclic amines onto halo-substituted arylalkynes over <i>N</i>-arylation under various catalytic conditions is described. The present work supports and confirms the mechanistic pathway of our recent work on the tandem synthesis of indolo- and pyrrolo-[2,1-<i>a</i>]isoquinolines via hydroamination followed by oxidative addition and not vice versa

Base-Mediated Selective Synthesis of Diversely Substituted <i>N</i>-Heterocyclic Enamines and Enaminones by the Hydroamination of Alkynes

Regio- and stereoselective alkynylation of various <i>N</i>-heterocycles <b>1a</b>–<b>l</b> using potassium and cesium salts in DMSO is described. Terminal alkynes <b>2a</b>–<b>k</b> and internal alkynes <b>4a</b>–<b>f</b> provided the kinetically stable <i>Z</i>-enamines <b>3a</b>–<b>l</b> and <b>5a</b>–<b>i</b> in good to excellent yields using KOH at 120 °C. Addition of heterocyclic amines to 1,3- and 1,4-diethynylbenzene <b>6a</b>–<b>b</b> provided the mixture of <i>E</i>/<i>Z</i> isomers with KOH; however, with Cs₂CO₃ selectively <i>Z</i>-isomers <b>7ab</b>–<b>db</b> were obtained by the hydroamination at one triple bond. This developed methodology also provides an easy and novel access for the synthesis of enaminones <b>10a</b>–<b>c</b>. The detailed work also supports the formation of <i>cis-</i>isomer by preferential addition of <i>o</i>-haloarylalkynes followed by intramolecular C2 arylation in the copper-catalyzed tandem synthesis of indolo and pyrrolo­[2,1-<i>a</i>]­isoquinolines

Base-Mediated Chemo- and Stereoselective Addition of 5‑Aminoindole/Tryptamine and Histamines onto Alkynes

Transition-metal-free chemo- and stereoselective addition of 5-aminoindole (<b>1a</b>), tryptamine (<b>1b</b>), and histamine (<b>1c</b>) to alkynes <b>2a</b>–<b>s</b> to synthesize the indolyl/imidazolyl enamines <b>3a</b>–<b>p</b>, <b>5a</b>–<b>o</b>, and <b>6a</b>–<b>e</b> using superbasic solutions of alkali-metal hydroxides in DMSO is described. The addition of N-heterocycles onto alkynes takes places chemoselectively without affecting the 1° amino groups (aromatic and aliphatic) of 5-aminoindole, tryptamine, and histamine. The stereochemistry of the products was found to be dependent upon reaction time; an increase in reaction time leads to the formation of a mixture of <i>E/Z</i> isomers and the thermodynamically stable <i>E</i> addition product. The chemoselective addition of N-heterocycle <b>1a</b> onto alkyne over thiophenol <b>7</b> and phenol <b>8</b> is supported by control experiments. Competitive experiments showed that 5-aminoindole was more reactive than tryptamine, and histamine was found to be the least reactive. The present methodology provides an efficient chemoselective method to synthesize a variety of (<i>Z</i>)-enamines of 5-aminoindole, tryptamine, and histamine without affecting the 1° amino group. The presence of the free amino group in enamines could be further used for synthetic elaboration, which proved to be highly advantageous for structural and biological activity assessments