2-Indolymethanols as 4-atom-synthons in oxa-Michael reaction cascade: access to tetracyclic indoles

• Published in: Chemical communications (Cambridge, England) Vol. 57; no. 71; pp. 8921 - 8924
• Main Authors: Han, Tian-Jiao, Wang, Min-Can, Mei, Guang-Jian
• Format: Journal Article
• Language: English
• Published: CAMBRIDGE Royal Soc Chemistry 06.09.2021; Royal Society of Chemistry
• Subjects: Acceleration; Alkenes; Chemistry; Chemistry, Multidisciplinary; Crystallography; Dehydration; Hydrogen bonding; Indoles; Michael reaction; NMR; Nuclear magnetic resonance; Physical Sciences; Regioselectivity; Science & Technology; Stereoselectivity; Substrates; 2-INDOLYLMETHANOLS; CYCLOADDITION; CATALYSIS; 3-INDOLYLMETHANOLS; ATOM ECONOMY; POLYCYCLIC INDOLES; EFFICIENT SYNTHESIS; ENANTIOSELECTIVE CONSTRUCTION; DERIVATIVES; CYCLIZATION
• ISSN: 1359-7345; 1364-548X
• DOI: 10.1039/d1cc03653j

The first Brønsted acid-catalyzed oxa-Michael reaction cascade of 2-indolylmethanols with trione alkenes was accomplished. By using this practical approach, a variety of tetracyclic indoles were readily created in an ordered sequence with excellent regio- and diastereoselectivity. 2-Indolylmethanols commendably served as four-atom synthons, as opposed to the common three-atom synthons in the previous literature reports. The regioselectivity issue was well handled by the employment of a strong Brønsted acid catalyst. In addition, its dual role in activation of substrates via hydrogen-bonding interaction and acceleration of subsequent intramolecular cyclization and dehydration was proposed to account for the high reaction efficiency. The first Brønsted acid-catalyzed oxa-Michael reaction cascade of 2-indolylmethanols as four-atom synthons with trione alkenes was accomplished.