Fiaud's Acid: A Brønsted Acid Catalyst for Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Alkene-1,4-diones

Sourav Chatterjee, Lukas Hintermann, Madhumita Mandal, Anushree Achari, Sreya Gupta, Parasuraman Jaisankar

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Abstract

Fiaud's acid (trans-1-hydroxy-2,5-diphenylphospholane 1-oxide), a phospholane-based phosphinic acid, is introduced as an efficient chiral Brønsted acid catalyst that mediates the asymmetric Friedel-Crafts alkylation of indoles with 2-butene-1,4-diones. With a catalyst loading of 10 mol %, the reaction proceeded smoothly to afford 2-(indol-3-yl)butane-1,4-diones in high yield (up to 82%) and high enantioselectivity (up to 91% ee, one such product showed enhanced ee of 98% after recrystallization). The reaction conditions are sufficiently mild to tolerate sensitive functionality at room temperature and are therefore suitable for the synthesis of complex targets.

Original languageEnglish
Pages (from-to)3426-3429
Number of pages4
JournalOrganic Letters
Volume19
Issue number13
DOIs
StatePublished - 7 Jul 2017

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