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Maleic Acid/Thiourea‐Catalyzed Dearomative ipso ‐Friedel–Crafts Reaction of Indoles to Produce Functionalized Spiroindolenines
Author(s) -
Ueda Jun,
Harada Shingo,
Kobayashi Mayu,
Yanagawa Mai,
Nemoto Tetsuhiro
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100215
Subject(s) - chemistry , thiourea , friedel–crafts reaction , maleic acid , diazo , catalysis , substituent , alkyl , combinatorial chemistry , organic chemistry , medicinal chemistry , copolymer , polymer
A dearomative spirocyclization of diazo‐functionalized indoles was developed under metal‐free conditions. Although the spiroindolenine architecture with a tertiary alkyl substituent at the 2‐position is a privileged scaffold of bioactive molecules, a general synthetic strategy has remained elusive. In this study, a dual catalyst system comprising maleic acid and Schreiner's thiourea was used to construct a spiroindolenine core that was inaccessible by rhodium or silver catalysis. Computational studies revealed a unique macrocyclic transition state consisting of the substrate, maleic acid, and thiourea cocatalyst, which lowered the activation energy of spirocyclization through multipoint mutual interactions.