Catalyzed Tandem C–N/C–C Bond Formation for the Synthesis of Tricyclic Indoles using Ir(III) Pyrazolyl-1,2,3-Triazolyl Complexes

A series of new pyrazolyl-1,2,3-triazolyl N<i>–</i>N′ bidentate donor ligands (<b>2a</b>–<b>c</b>, <b>3a</b>–<b>d</b>) were prepared via Cu­(I)-catalyzed Huisgen cycloaddition reactions between 1-propargylpyrazoles and 4-substituted phenyl azides. The electron-withdrawing ability of the substituents follows the trend PhCH<sub>2</sub> < <i>p</i>-CH<sub>3</sub>Ph < Ph < <i>p</i>-CF<sub>3</sub>Ph < <i>p</i>-NO<sub>2</sub>Ph, as illustrated in the gradual downfield shift of the 1,2,3-triazolyl-<i>C</i>4′ <sup>13</sup>C NMR resonances. A series of Rh and Ir complexes containing these pyrazolyl-1,2,3-triazolyl or bis­(pyrazol-1-yl)­methane donor ligands of general formulae [Ir­(N–N′)­Cp*Cl]­X (X = BAr<sup>F</sup><sub>4</sub>, BPh<sub>4</sub>; <b>5</b>–<b>8</b>), [Rh­(N–N′)­Cp*Cl]­X (X = BAr<sup>F</sup><sub>4</sub>, BPh<sub>4</sub>; <b>9</b>–<b>11</b>), and [Rh­(N–N′)­(CO)<sub>2</sub>]­BAr<sup>F</sup><sub>4</sub> (<b>13</b>–<b>16</b>) (BAr<sup>F</sup><sub>4</sub> = tetrakis­[3,5-bis­(trifluoromethyl)­phenyl]­borate) were synthesized and fully characterized. The solid-state structures of <b>5</b>, <b>6a′</b>, <b>6b</b>, <b>7b</b>, <b>8</b>, <b>9</b>, <b>10a</b>, <b>10a′</b>, <b>11</b>, and <b>15c</b> were determined by X-ray diffraction studies. As the electron-withdrawing strength of the phenylene substituent on the triazolyl ring is increased, the M–N3′(triazole) bond length becomes longer. The efficiency of these Rh and Ir complexes as catalysts for the synthesis of tricyclic indoles via tandem C–N and C–C bond formation reactions from 2-(hydroxyalk-1-ynyl)­anilines (<b>17S</b>–<b>20S</b>) was assessed. The Ir­(III) catalysts were the most efficient for the C–C bond formation step, and the Rh­(I) complexes <b>13</b>–<b>16</b> were the most efficient catalysts for C–N bond formation, where TOFs >1000 h<sup>–1</sup> were reached. However, the Ir­(III) complexes <b>5</b>–<b>8</b> were found to be the only active catalysts for the tandem C–N and C–C bond formation, as the Rh­(I) complexes were not active catalysts for the C–C bond formation step. The C–N bond formation leading to the formation of indoles was found to proceed via two reaction pathways with 2-(hydroxyalk-1-ynyl)­aniline substrates: (a) hydroamination and (b) hydroalkoxylation–Lewis acid mediated isomerization. Pathway (b) is likely to be the main pathway in the formation of indoles starting with 2-(hydroxyalk-1-ynyl)­aniline substrates <b>17S</b>, <b>18S</b>, and <b>20S</b>.