ZrCl₄-Mediated Regio- and Chemoselective Friedel–Crafts Acylation of Indole

Abstract

An efficient method for regio- and chemoselective Friedel-Crafts acylation of indole using acyl chlorides in the presence of ZrCl(4) has been discovered. It minimizes/eliminates common competing reactions that occur due to high and multiatom-nucleophilic character of indole. In this method, a wide range of aroyl, heteroaroyl alkenoyl, and alkanoyl chlorides undergo smooth acylation with various indoles without NH protection and afford 3-acylindoles in good to high yields.

Metal-organic framework MIL-53(Al): synthesis, catalytic performance for the Friedel-Crafts acylation, and reaction mechanism

“…However, when the nonpolar cyclohexane was used as solvent, the conversion of indole was only 89.6%; the selectivity of 3-acylindole dropped to 79.5%; and the yield of 3-acylindole decreased to 86.2%. These results were consistent with previous literature [31] in that polar solvents were more beneficial to a Friedel-Crafts acylation of indole with benzoyl chloride (because indole and benzoyl chloride are both polar materials). According to the theory of similar compatibility, it is easy to dissolve reactants in polar solventsa situation that favors full contact between two reactants and thus improves conversion.…”

“…Friedel-Crafts acylation reactions mostly use homogeneous catalysts such as AlCl 3 [34] and ZrCl 4 [31]. The Lewis acid sites of the catalysts are catalytic-active centers, as when AlCl 3 was used as a Lewis acid catalyst for FriedelCrafts acylation and the Lewis acid Al 3+ sites were found to be catalytic-active centers.…”

Identification and analytical properties of new synthetic cannabimimetics bearing 2,2,3,3-tetramethylcyclopropanecarbonyl moiety

“…These chemical shifts in 1 H and 13 C spectra of compound 16 are not characteristic for indole derivatives and differ substantially from the data for compounds 2 and 10 and from Refs. [20,26,27] data. We suggested that these could be rationalized by a mesomeric structure where positive charge is delocalized along a conjugation chain from indole N (resonance structure 16(N + )) to furan O (resonance structure 16(O + )) (Fig.…”

A Simple, Effective, Green Method for the Regioselective 3-Acylation of Unprotected Indoles

“…Regioselectivity in the 3-acylation of indoles has been an interesting and challenging subject in organic synthesis. A wide range of 3-acylindoles was synthesized by several methods such as Friedel-Crafts acylation [5][6][7][8][9][10][11][12], Vilsmeier-Haack type reaction [4,13], α-aminocarbonyl compounds with palladium [14], carbamoyl electrophiles [2], α-oxocarboxylic acids [15][16][17], and nitrilium salt with palladium [18]. Among those, Friedel-Crafts acylation of free (NH) indoles is definitely the simplest way [19], however, low yields were observed due to competing substitution at the 1-position.…”