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Issue 9, 2017
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Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

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Abstract

The direct CH-alkylation of indoles using carboxylic acids is presented for the first time. The catalytic system based on the combination of Co(acac)3 and 1,1,1-tris(diphenylphosphinomethyl)-ethane (Triphos, L1), in the presence of Al(OTf)3 as co-catalyst, is able to perform the reductive alkylation of 2-methyl-1H-indole with a wide range of carboxylic acids. The utility of the protocol was further demonstrated through the C3 alkylation of several substituted indole derivatives using acetic, phenylacetic or diphenylacetic acids. In addition, a careful selection of the reaction conditions allowed to perform the selective C3 alkenylation of some indole derivatives. Moreover, the alkenylation of C2 position of 3-methyl-1H-indole was also possible. Control experiments indicate that the aldehyde, in situ formed from the carboxylic acid hydrogenation, plays a central role in the overall process. This new protocol enables the direct functionalization of indoles with readily available and stable carboxylic acids using a non-precious metal based catalyst and hydrogen as reductant.

Graphical abstract: Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

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Publication details

The article was received on 11 May 2017, accepted on 11 Jul 2017 and first published on 26 Jul 2017


Article type: Edge Article
DOI: 10.1039/C7SC02117H
Citation: Chem. Sci., 2017,8, 6439-6450
  • Open access: Creative Commons BY license
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    Cobalt-catalysed reductive C–H alkylation of indoles using carboxylic acids and molecular hydrogen

    J. R. Cabrero-Antonino, R. Adam, K. Junge and M. Beller, Chem. Sci., 2017, 8, 6439
    DOI: 10.1039/C7SC02117H

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