An organocatalytic asymmetric Friedel-Crafts reaction of 2-substituted indoles with aldehydes: enantioselective synthesis of α-hydroxyl ketones by low loading of chiral phosphoric acid

• Published in: Chemical communications (Cambridge, England) Vol. 56; no. 16; pp. 2499 - 252
• Main Authors: Deng, Xiong-fei, Wang, Ying-wei, Zhang, Shi-qi, Li, Ling, Li, Guang-xun, Zhao, Gang, Tang, Zhuo
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 25.02.2020; Royal Society of Chemistry
• Subjects: Aldehydes; Alkylation; Asymmetry; Carbonyl compounds; Carbonyls; Chemistry; Chemistry, Multidisciplinary; Crystallography; Enantiomers; Friedel-Crafts reaction; Indoles; Ketones; Phosphoric acid; Physical Sciences; Science & Technology; Substitutes; FUNCTIONALIZATION; ACTIVATION; FURANS; AMINES; ALKYLATION; COMPLEXES; RECENT PROGRESS; CATALYST; STRATEGIES
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/c9cc09637j

Hydroxyl alkylation of indoles by Friedel-Crafts reaction with a carbonyl compound is a useful strategy. However, the reaction was restricted to ketones due to the easy formation of a bisindole byproduct. Therefore, hydroxyl alkylation of an aldehyde with indole is confronted with great challenges. Here, we report an efficient strategy for asymmetric hydroxyl alkylation of 2-substituted indoles with aldehydes under 0.1 mol% chiral phosphoric acid. A series of α-hydroxyl ketones were obtained in high yields (up to 99%) and good enantioselectivities (up to 97%). Hydroxyl alkylation of indoles by Friedel-Crafts reaction with a carbonyl compound is a useful strategy.