Stereoselective Alkylation of Indole with 5-Arylidene-Meldrum’s Acids in the Presence of Organocatalysts

Author(s): Ewelina Najda-Mocarska, Anna Zakaszewska, Karolina Janikowska, Slawomir Makowiec*.

Journal Name: Letters in Organic Chemistry

Volume 15 , Issue 10 , 2018

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Graphical Abstract:


Background: Indole motif is frequently present in biologically active compounds. Enantiomerically pure or enriched 2,2-dimethyl-5-(aryl(1H-indol-3-yl)methyl)-1,3-dioxane-4,6-diones can be considered as a convenient starting point for the synthesis of a indole ring fused with cyclic ketones with biological activity. Preparation of chiral 2,2-dimethyl-5-(aryl(1H-indol-3-yl)methyl)-1,3-dioxane- 4,6-diones requires the reaction of indole with 2,2-dimethyl-5-arylidene-1,3-dioxane-4,6-diones in the presence of chiral catalysts or other source of chiral induction.

Methods: Enantioselective Friedel-Crafts alkylation of indole has been performed with 2,2-dimethyl-5- arylidene-1,3-dioxane-4,6-diones in the presence of organocatalysts to give 5-((1H-indol-3- yl)(aryl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-diones. Broad scope of organocatalysts as well as various temperatures and solvents used for the reaction were tested.

Results: 2,2-Dimethyl-5-(aryl(1H-indol-3-yl)methyl)-1,3-dioxane-4,6-diones were obtained with quantitative yield and enantiomeric ratio 1:3 using thiourea organocatalyst. Also a new spectroscopic method for discrimination of 5-((1H-indol-3-yl)(aryl)methyl)-2,2-dimethyl-1,3-dioxane-4,6-diones enantiomers was developed.

Conclusion: Enantioselective Friedel-Crafts alkylation of indole has been developed. In the presence of thiourea catalysts, 2,2-dimethyl-5-arylidene-1,3-dioxane-4,6-diones react with indole to give 2,2- dimethyl-5-(aryl(1H-indol-3-yl)methyl)-1,3-dioxane-4,6-diones with good yields and reasonable ee.

Keywords: Stereoselective 1, 3-dioxane-4, 6-dione, heteroaromatic, thiourea organocatalyst, alkylation, Meldrum`s acid, ketone.

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Article Details

Year: 2018
Page: [883 - 890]
Pages: 8
DOI: 10.2174/1570178615666180503150327
Price: $65

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