Alkylation of Indoles with α,β‐Unsaturated Ketones using Alumina in Hexanes

Abstract

We evaluated the influence of solvent on the alumina-promoted C3-alkylation of indoles with α,β-unsaturated ketones. We found that lipophilic solvents were generally superior to hydrophilic ones with hexanes offering the 3-alkyl indole products in high yields. Thus, we demonstrate an inexpensive and procedurally simple new process that pairs acidic alumina with hexanes to achieve this important Michael alkylation. The substrate scope includes twenty-four examples with reaction yields ranging from 61 to 96%. Scheme 1. Lewis Acids used for alkylation of indoles with α,βunsaturated ketones.

Efficient Synthesis of Cannabigerol, Grifolin, and Piperogalin via Alumina-Promoted Allylation

“…These results prompted an investigation into alternative reaction conditions for this process. In the context of heterogeneous synthetic methods development research, , we recently identified the pairing of activated acidic alumina with hydrophobic solvents such as hexanes or 1,2-dichloroethane (DCE) as useful conditions for promoting an indole alkylation reaction . When analogous conditions were applied to the reaction of 1 with 2 , a relatively selective and clean formation of 3 in 34% yield (Table , entry 1) was observed.…”

“…Chemical shifts in 1 H NMR and 13 C NMR spectra are reported in parts per million (ppm) with reference to residual CHCl 3 (δ H 7.26) and CDCl 3 (δ C 77. 16). Peak multiplicities are reported using the following abbreviations: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; m, multiplet.…”

Syntheses of N-Alkyl 2-Arylindoles from Saturated Ketones and 2-Arylethynylanilines via Cu-Catalyzed Sequential Dehydrogenation/Aza-Michael Addition/Annulation Cascade

“…Subsequently, indole I was generated via the protonation of the copper complex H . Finally, the nucleophilic attack of I on the α,β-unsaturated ketone 2a occurred to afford 2,3-dialkylindole 4oa through a copper-assisted 1,4-Michael addition …”

Arene Diazonium Tetrafluoroborate Salts: Novel Lewis Acid Catalysts for Friedel‐Crafts Alkylation of Indoles with α,β‐Unsaturated Ketones

“…[6] Since then, chemists had tried to use a series of Lewis acids to catalyze this reaction and achieved good results. These Lewis acid catalysts include alumina, [7] Yb(OTF) 3 , [8] InCl 3 , [9] Bi(NO 3 ) 3 , [10] I 2 , [11] Br 2 , [12] SmI 3 , [13] NIS, [14] and other types of Lewis acids. [15] To our knowledge, there is no report on the alkylation of indole catalyzed by diazonium salts.…”