A Journey Across Recent Advances in Catalytic and Stereoselective Alkylation of Indoles

Abstract

In this Account our recent results in relation to the catalytic and stereoselective Friedel-Crafts (FC) alkylation of indoles are described. Over the last decade, remarkable efforts have been devoted towards the replacement of the primal approaches with new more efficient, reliable, and environmentally benign strategies for the functionalization of indoles. Moreover, the emerging area of catalytic asymmetric FC processes is addressed and some examples of enantioselective alkylations of indoles via 1,4-addition to a,b-unsaturated systems and asymmetric ring-opening reaction of aromatic epoxides are described.

Modern Friedel-crafts chemistry. part 31. An efficient synthetic approach to mono-, di- and triphenylindans via direct Friedel-crafts cyclialkylaion of selected phenylated alkanols

“…aq. NH 4 Cl soln and the product was extracted with ether and dried over anhydrous magnesium sulfate. 17 and purification by chromatography (neutral alumina, petroleum 40-60 °C eluant) gave 13 (79%) as a yellowish oil, R f 0.4 (silica gel, petroleum 60-80 °C/AcOEt (ii) Cycliacylation of 3,3,3-triphenylpropanoyl chloride with AlCl 3 catalyst in carbon disulfide solvent gave 76% of crude product which upon crystallization from ethyl alcohol gave 69% of pure 3,3-diphenylindanone as white crystals m.p.…”

“…[1][2][3] In recent years, we have directed part of our research efforts to study both the synthetic utilities and the mechanistic aspects of these important reactions. [4][5][6] These efforts not only illustrated the broad …”

Intramolecular Friedel-Crafts Reaction of Indoles with Carbonyl Groups: A Simple Synthesis of 3- and 4-Substituted β-Carbolin-1-ones

“…On the contrary, only two old examples of the simple intramolecular FC reaction with carbonyl compounds exist in the literature, 11,12 so that it has not even been mentioned in the most recent review. 8 Herein we report a short and efficient synthesis of a series of 3-aryl-, 4-aryl-, and 4-alkyl-b-carbolin-1-ones, that was achieved using this neglected, yet simple reaction.…”

“…14 This observation is consistent with the increase of yield from 3d to 3b. Based on recent work 8 on the use of indium salts as mild Lewis acids in the promotion of Friedel-Crafts-like reactions on indoles, we repeated the cyclization of 3a using indium trichloride instead of TFA. Cyclization to 4a was obtained with a slightly improved yield (69% vs. 63%).…”

“…An accurate perusal of the literature showed that this method has been almost completely neglected. In the recent years several approaches to intramolecular annulation of indoles, such as Michael addition to enones 8,9 or Pd-catalyzed allylic alkylation, 8,10 have been devised. On the contrary, only two old examples of the simple intramolecular FC reaction with carbonyl compounds exist in the literature, 11,12 so that it has not even been mentioned in the most recent review.…”