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Chemoselective N‐Alkylation of Indoles in Aqueous Microdroplets
Author(s) -
Gnanamani Elumalai,
Yan Xin,
Zare Richard N.
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201913069
Subject(s) - alkylation , reagent , indole test , yield (engineering) , chemistry , reactivity (psychology) , catalysis , aqueous solution , combinatorial chemistry , organic chemistry , phase (matter) , aqueous two phase system , computational chemistry , materials science , medicine , alternative medicine , pathology , metallurgy
Abstract Many reactions show much faster kinetics in microdroplets than in the bulk phase. Most reported reactions in microdroplets mirror the products found in bulk reactions. However, the unique environment of microdroplets allows different chemistry to occur. In this work, we present the first chemoselective N‐alkylation of indoles in aqueous microdroplets via a three‐component Mannich‐type reaction without using any catalyst. In sharp contrast, bulk reactions using the same reagents with a catalyst yield exclusively C‐alkylation products. The N‐alkylation yield is moderate in microdroplets, up to 53 %. We extended the scope of the microdroplet reaction and obtained a series of new functionalized indole aminals, which are likely to have biological activities. This work clearly indicates that microdroplet reactions can show reactivity quite different from that of bulk‐phase reactions, which holds great potential for developing novel reactivities in microdroplets.