Open AccessHypoiodite-Catalyzed Oxidative Umpolung of Indoles for Enantioselective Dearomatization
Author(s) -
H. Tanaka,
Naoya Ukegawa,
Muhammet Uyanik,
Kazuaki Ishihara
Publication year - 2022
Publication title -
journal of the american chemical society
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.115
H-Index - 612
eISSN - 1520-5126
pISSN - 0002-7863
DOI - 10.1021/jacs.2c01852
Subject(s) - umpolung , chemistry , enantioselective synthesis , indole test , reactivity (psychology) , catalysis , oxidative phosphorylation , pyrazole , hypervalent molecule , nitrogen atom , organocatalysis , combinatorial chemistry , stereochemistry , organic chemistry , alkyl , biochemistry , reagent , medicine , alternative medicine , pathology , nucleophile
Here we report the oxidative umpolung of 2,3-disubstituted indoles toward enantioselective dearomative aza-spirocyclization to give the corresponding spiroindolenines using chiral quaternary ammonium hypoiodite catalysis. Mechanistic studies revealed the umpolung reactivity of C3 of indoles by iodination of the indole nitrogen atom. Moreover, the introduction of pyrazole as an electron-withdrawing auxiliary group at C2 suppressed a competitive dissociative racemic pathway, and enantioselective spirocyclization proceeded to give not only spiropyrrolidines but also four-membered spiroazetidines that are otherwise difficult to access.