3-Alkylated indoles by reduction of sulfonyl indoles under flow chemical conditions

Abstract

Reduction of 3-(1-arylsulfonylalkyl) indoles (sulfonyl indoles) using polymer-supported sodium borohydride under flow chemical conditions allows an efficient synthesis of 3-alkylindoles with a notable waste minimization and reduced solvent consumption. The flow conditions can be also applied to the synthesis of sulfonyl indoles which can be obtained by a three-component coupling of indoles with aldehydes and ptoluenesulfinic acid. Using the two-step flow chemical approach, 3-alkylindoles can be directly obtained from their remote indole and aldehyde precursors.

Arenesulfonyl indole: new precursor for diversification of C-3 functionalized indoles

“…Use of flow chemical conditions for carrying out the reductive desulfonylation of arenesulfonyl indoles using polymer-supported sodium borohydride has been carried out by Petrini and co-workers 56 to synthesize 3-alkyl indoles in 57–85% yields.…”

Continuous Flow Synthesis of Heterocycles: A Recent Update on the Flow Synthesis of Indoles

“…Moreover, using a slightly different setup, the gram-scale preparation of bis(indolyl)methanes derivative 81a was performed, obtaining 12.4 g with an operation time of 5 h and 46 min (Scheme 28). A further contribution by Palmieri and coworkers presented the oxidative transformation of sulfonyl indoles 82 into 3-alkylidene-2-oxindoles 83 using the continuous flow approach [109]. The reaction involved indole ring oxidation mediated by N-chlorosuccinimide (NCS), followed by the elimination of arylsulfinic acid to introduce exocyclic unsaturation.…”

“…Very recently, the same group presented the continuous flow preparation of 3-alkylindoles 85 through the polymer-supported sodium borohydride reduction of 3-(1-arylsulfonylalkyl) indoles 84 (sulfonyl indoles) [ 109 ]. The reaction stoichiometry, reactant concentrations, residence time, and solvent were judiciously optimized by using a flow system composed of two syringe pumps, a three-way valve, a packed bed reactor, and a back-pressure regulator.…”