Copper-Catalyzed Decarboxylative N-Arylation of Indole-2-carboxylic Acids

Abstract

A novel decarboxylative N-arylation of indole-2-carboxylic acids with aryl halides is developed. The reaction proceeds efficiently in the presence of Cu2O as the catalyst to give the corresponding N-aryl indoles in high yields. This synthetic method shows good functional group tolerance and offers an alternative route to construct N-aryl indoles.

Recent Progress Concerning the N-Arylation of Indoles

“…An alternative approach to the N -arylation of indoles makes use of 2-indolylboronic acids ( Scheme 29 ) [ 143 ]. The starting carboxylic acids S29-1 react with aryl bromides or aryl iodides in the presence of catalytic amounts of copper oxide and potassium phosphate as a base.…”

Functionalization of superparamagnetic Fe3O4@SiO2nanoparticles with a Cu(II) binuclear Schiff base complex as an efficient and reusable nanomagnetic catalyst forN‐arylation of α‐amino acids and nitrogen‐containing heterocycles with aryl halides

“…[ 7,8 ] The first copper catalyzed C–N bond formation was developed by Ullman and Goldberg. [ 9,10 ] Various types of N ‐arylation have been reported in the literature that some examples come as follows: N ‐arylation of imidazoles, [ 11–16 ] Cu(I)‐catalyzed N ‐arylation of indoles, [ 17 ] C–N coupling of aniline with terminal alkynes (synthesis of α‐ketoamides), [ 18 ] copper‐mediated C–N coupling reaction of azido compounds and aryl halides, [ 19 ] N ‐arylation of aryl halides with alkyl amine using CuBr catalyst which benefits from phosphoramidite as a ligand, [ 20 ] Cu(I)‐catalyzed N ‐arylation of pyrazoles, [ 21 ] N ‐arylation of aryl iodide with hypervalent aryl siloxanes by Cu (OAc) 2 along with a ligand, [ 22 ] N ‐arylation of α‐amino acids catalyzed by Cu(I), [ 23–25 ] cross‐coupling reaction of aryl halides to aryl amines catalyzed by Cu 2 O in solution of ammonia, [ 26 ] N ‐alkynylation of amides catalyzed by Cu(I), [ 27 ] Cu(I)‐amidation catalyzed of aryl halides, [ 28–30 ] Ullmann‐type N ‐arylation of anilines, [ 31 ] Cu‐catalyzed intramolecular adjacent C–N coupling (asymmetric synthesis of atropisomeric compounds), [ 32 ] Cu/ N , N ′‐dibenzyloxalamide‐catalyzed N ‐arylation of heteroanilines, [ 33 ] Cu‐catalyzed N ‐arylation of sulfoximines, [ 34 ] Cu‐catalyzed decarboxylative N ‐arylation of indole‐2‐carboxylic acids, [ 35 ] and Cu‐catalyzed intramolecular benzylic C–H amination for the synthesis of isoindolinones. [ 36 ]…”