N‐Heterocyclic‐Carbene‐Catalyzed Synthesis of 2‐Aryl Indoles

Abstract

A convergent and efficient transition‐metal‐free catalytic synthesis of 2‐aryl‐indoles has been developed. The interception of a highly reactive and transient aza‐ortho‐quinone methide by an acyl anion equivalent generated through N‐hetereocyclic carbene catalysis is central to this successful strategy. High yields and a wide scope as well as the streamlined synthesis of a kinase inhibitor are reported.

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…29 Other methods involve the transformation of heterocycles, 30 the conversion of indolines into indoles, 31 the synthesis of o-alkynylanilines, 32 the reduction of oxindoles to indoles, 33 synthetic methods using arynes, 34 the reductive cyclization of nitrobenzene derivatives 35 and catalysis using N-heterocyclic carbenes. 36 Owing to the importance of the indole as a scaffold in natural products and biologically active compounds, a plethora of reviews and several chapters have been published in this eld. In a continuation of our interest in heterocyclic chemistry [65][66][67] and the applications of named reactions in the total synthesis of natural products, [68][69][70][71][72][73][74][75] in this review we aim to highlight the synthesis of indoles as a moiety in selected alkaloids.…”

“… 29 Other methods involve the transformation of heterocycles, 30 the conversion of indolines into indoles, 31 the synthesis of o -alkynylanilines, 32 the reduction of oxindoles to indoles, 33 synthetic methods using arynes, 34 the reductive cyclization of nitrobenzene derivatives 35 and catalysis using N -heterocyclic carbenes. 36 …”

Access to Biaryl Sulfonamides by Palladium-Catalyzed Intramolecular Oxidative Coupling and Subsequent Nucleophilic Ring Opening of Heterobiaryl Sultams with Amines

“…Notably, atropisomerism along a C-2­(indole)-C­(aryl) axis has been the least studied . 2-Arylindoles have been prepared historically by Fischer and Bischler–Mohlau syntheses, later more extensively by Larock indole synthesis, and very recently by Scheidt employing N-heterocylic carbene as a catalyst . Functionalization of indoles with aromatic hydrocarbons by palladium- or copper-catalyzed oxidative coupling was successfully achieved enabling regioselective C-2 arylation of indoles.…”

“…6 2-Arylindoles have been prepared historically by Fischer 7 and Bischler−Mohlau 8 syntheses, later more extensively by Larock indole synthesis, 9 and very recently by Scheidt employing N-heterocylic carbene as a catalyst. 10 Functionalization of indoles with aromatic hydrocarbons by palladium-11 or copper-catalyzed 12 oxidative coupling was successfully achieved enabling regioselective C-2 arylation of indoles. Although the current literature is quite resourceful warranting broad applications to the preparation of functionalized 2-arylindoles, whether the druglike scaffold II could be readily accessible remains a question.…”