Reaction of indoles with aromatic fluoromethyl ketones: an efficient synthesis of trifluoromethyl(indolyl)phenylmethanols using K2CO3/n-Bu4PBr in water.

Thanigaimalai Pillaiyar,Gregor Schnakenburg,Masoud Sedaghati

doi:10.3762/bjoc.16.71

Thanigaimalai Pillaiyar, Gregor Schnakenburg + Show 1 more

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https://doi.org/10.3762/bjoc.16.71

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Journal: Beilstein journal of organic chemistry	Publication Date: Apr 20, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: University of Bonn

Abstract

A new, mild and efficient protocol for the synthesis of trifluoromethyl(indolyl)phenylmethanols by the reaction of indoles with a variety of aromatic fluoromethyl ketones in the presence of K2CO3 (15 mol %) and n-Bu4PBr (15 mol %) in water. The desired products were obtained in good to excellent yields without requiring a column chromatographic purification. The reusability of the catalytic system and large-scale synthesis of indolyl(phenyl)methanols, which would further transform into biological active indole-derived compounds, are further advantages of this protocol.

Highlights

Organofluorine compounds have attracted much attention due to their potential biological applications in medicinal and agricultural sciences
Trifluoromethyl-substituted (1H-indol-3-yl)methanol derivatives can be synthesized by Friedel–Crafts hydroxyalkylation reactions of indoles with trifluoromethyl ketones in the presence of either Lewis/Bronsted acid catalysts
In our continuous effort of synthesizing indole derivatives [2931], we report an efficient synthesis of multiple halogensubstituted (1H-indol-3-yl)methanol derivatives in the presence of potassium carbonate and tetrabutylphophonium bromide, which mediate the reaction in water through the formation of the interface between organic and aqueous phases

Summary

Introduction

Organofluorine compounds have attracted much attention due to their potential biological applications in medicinal and agricultural sciences. In our continuous effort of synthesizing indole derivatives [2931], we report an efficient synthesis of multiple halogensubstituted (1H-indol-3-yl)methanol derivatives in the presence of potassium carbonate and tetrabutylphophonium bromide, which mediate the reaction in water through the formation of the interface between organic and aqueous phases. The advantageous of this reaction include high yields, no column chromatography, broad substrate scope, multiscale synthesis, and recyclable of the catalyst (Figure 2C).

Results

Conclusion