Cobalt-catalysed reductive C-H alkylation of indoles using carboxylic acids and molecular hydrogen

Jose R. Cabrero-Antonino, Rosa Adam, Kathrin Junge, Matthias Beller

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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.

Original languageEnglish
Pages (from-to)6439-6450
Number of pages12
JournalChemical Science
Volume8
Issue number9
DOIs
StatePublished - 2017
Externally publishedYes

Fingerprint

Dive into the research topics of 'Cobalt-catalysed reductive C-H alkylation of indoles using carboxylic acids and molecular hydrogen'. Together they form a unique fingerprint.

Cite this