Chemoselective N-Alkylation of Indoles in Aqueous Microdroplets
Elumalai Gnanamani1,2, Xin Yan1,3, Richard N Zare1,2
1Department of Chemistry, Stanford University, 333 Campus Drive, Stanford, CA, 94305-5080, USA.
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.
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