Brønsted acid-catalyzed C6 functionalization of 2,3-disubstituted indoles for construction of cyano-substituted all-carbon quaternary centers

• Published in: Organic & biomolecular chemistry Vol. 21; no. 17; pp. 3691 - 3696
• Main Authors: Huang, Wen-Jun, Liu, Li-Xia, Zhou, Yong-Gui, Wu, Bo, Jiang, Guo-Fang
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 03.05.2023; Royal Society of Chemistry
• Subjects: Aldehydes; Amides; Amines; Carbon; Chemistry; Chemistry, Organic; Indoles; Intermediates; Oxidation; Physical Sciences; Quinones; Science & Technology; Substitutes; H FUNCTIONALIZATION; DRUG LEADS; 3-INDOLYLMETHANOLS; NATURAL-PRODUCTS; ALKYLATION; ARYLATION; ACCESS; ALKALOIDS
• ISSN: 1477-0520; 1477-0539; 1477-0539
• DOI: 10.1039/d3ob00412k

We report a Brønsted acid-catalyzed C6 functionalization of 2,3-disubstituted indoles with 2,2-diarylacetonitriles for efficient construction of cyano-substituted all-carbon quaternary centers with excellent yields. The synthetic utility was demonstrated by the conversion of the cyano-group which enables the divergent preparation of aldehydes, primary amines and amides. Control experiments suggested that this process involves C-H oxidation of 2,2-diarylacetonitriles to in situ generate δ , δ -disubstituted p -quinone methide intermediates. This protocol provides an efficient method for C6 functionalization of 2,3-disubstituted indoles to construct all-carbon quaternary centers. The construction of cyano-substituted all-carbon quaternary centers via Brønsted acid-catalyzed direct C6 functionalization of 2,3-disubstituted indoles with 2,2-diarylacetonitriles is reported.