Transition‐Metal‐Free C3 Arylation of Indoles with Aryl Halides

Abstract

Herein, we report an unprecedented transition metal-free, coupling of indoles with aryl halides. The reaction is promoted by KOtBu and is regioselective for C3 over nitrogen. The use of degassed solvents devoid of oxygen is necessary for the success of the transformation. Preliminary studies implicate a hybrid mechanism that involves both aryne intermediates and non-propagative radical processes. Electron transfer is also a distinct possibility. These conclusions were substantiated by EPR data, isotopic labeling studies, and the use of radical scavengers and electron transfer inhibitors.

Catalytic Au(i)/Au(iii) arylation with the hemilabile MeDalphos ligand: unusual selectivity for electron-rich iodoarenes and efficient application to indoles

“…The arylation of indoles with transition metal catalysts has garnered tremendous efforts over the last two decades and Pd clearly occupies the forefront position (Scheme 3). 25,26 The main challenge of the transformation is the control of regioselectivity in the absence of directing groups. Most transition metals tend to intrinsically favour C2 arylation,25,27 while direct arylations of indoles at the C3 position remain scant 28,29…”

Recent Advances in the Transition-Metal-Free Arylation of Hetero­arenes

“…In 2017, Wu and Chen reported a method for the arylation of indoles with aryl halides under transition-metal-free conditions (Scheme 32). 41 The use of degassed oxygen-free solvents is essential for this protocol, promoted by t-BuOK, to work. The reaction used NH-unprotected indoles and C-3 arylation was preferred over N-arylation.…”

Nucleophile-intercepted Beckmann fragmentation reactions

“…[17][18][19][20] Our research group has been interested in the development of novel reactions involving indoles and related heterocycles for some time. [21][22][23][24][25][26][27][28] In this context, we have previously reported the (3 + 2) annulation between 3-substituted indoles and various oxyallyl cations generated from a-haloketones to give bicycloketone 3 (Scheme 1). 23 In the following work, we converted 3 to the corresponding oxime with NH 2 OH$HCl.…”