Solid Acid‐Catalysed Michael‐Type Conjugate Addition of Indoles to Electron‐Poor CC Bonds: Towards High Atom Economical Semicontinuous Processes

Abstract

In this paper a novel application of solid acid catalysts in the chemoselective Friedel±Crafts (FC) alkylation of indoles is reported. The optimal protocol allows highly functionalised indolyl compounds to be synthesised in excellent yields through conjugate addition of indoles with a,b-unsaturated ketones and nitro compounds. Finally, the use of commercial Amberlyst-15 as the heterogeneous catalyst for highly atom efficient continuous and semicontinuous Friedel±Crafts processes is described.

Few Layer 2D Pnictogens (P & Sb) Catalyze the Alkylation of Soft Nucleophiles with Esters

“…Current methodologies at laboratory 34 or industrial scale 35 for this reaction are still based on Friedel-Crafts type chemistry, with isobutylene or tert-butyl alcohol as alkylating agents under very strong reaction conditions. These harsh protocols are substratelimiting and particularly unselective in the presence of aromatic rings 36 , despite synthetically elaborated, energetically richer and expensive tert-butylated reagents have been prepared on purpose to mitigate these drawbacks 37 .…”

Few Layer 2D Pnictogens (P & Sb) Catalyze the Alkylation of Soft Nucleophiles with Esters

“…Current methodologies at laboratory 34 or industrial scale 35 for this reaction are still based on Friedel-Crafts type chemistry, with isobutylene or tert-butyl alcohol as alkylating agents under very strong reaction conditions. These harsh protocols are substrate-limiting and particularly unselective in the presence of aromatic rings, 36 despite synthetically elaborated, energetically richer and expensive tert-butylated reagents have been prepared on purpose to mitigate these drawbacks. 37 Table 1 shows the results for the reaction between benzyl alcohol Isotopic experiments with 18 O-1 confirm that the oxygen atom of the alcohol stays intact in product 3, which suggests that an ester C-O alkyl cleavage (AL mechanism) operates, as reported with superacids (H 0 <0) such as HSO 3 F-SbF 5 -SO 2 .…”

“…or industrial scale35 for this reaction are still based on Friedel-Crafts type chemistry, with isobutylene or tert-butyl alcohol as alkylating agents under very strong reaction conditions. These harsh protocols are substrate-limiting and particularly unselective in the presence of aromatic rings,36 despite synthetically elaborated, energetically richer and expensive tert-butylated reagents have been prepared on purpose to mitigate these drawbacks. 37Table 1shows the results for the reaction between benzyl alcohol 1 and tertbutyl acetate 2, in the presence of different catalysts.…”

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

“…Dried Amberlyst ® A26 (hydroxide form) was shown to be the most efficient species resulting in good to excellent yields. The synthesis of 176 in flow was demonstrated, the simple packed column system allowed easy isolation of the product and the catalyst activity was maintained over 10 hours [194]. A similar approach using Amberlyst ® IRA-900 (OH form) was employed for the Michael Organocatalysis has been widely employed for Michael addition reactions and several metal-free enantioselective versions have been reported over the years [101,195,196].…”