Premium
Palladium‐Catalyzed Dearomative syn ‐1,4‐Carboamination with Grignard Reagents
Author(s) -
Tang Conghui,
Okumura Mikiko,
Zhu Yunbo,
Hooper Annie R.,
Zhou Yu,
Lee YuHsuan,
Sarlah David
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201905021
Subject(s) - palladium , chemistry , reagent , enantioselective synthesis , desymmetrization , catalysis , combinatorial chemistry , allylic rearrangement , organic chemistry , naphthalene
A protocol for palladium‐catalyzed dearomative functionalization of simple, nonactivated arenes with Grignard reagents has been established. This one‐pot method features a visible‐light‐mediated [4+2] cycloaddition between an arene and an arenophile, and subsequent palladium‐catalyzed allylic substitution of the resulting cycloadduct with a Grignard reagent. A variety of arenes and Grignard reagents can participate in this process, forming carboaminated products with exclusive syn ‐1,4‐selectivity. Moreover, the dearomatized products are amenable to further elaborations, providing functionalized alicyclic motifs and pharmacophores. For example, naphthalene was converted into sertraline, one of the most prescribed antidepressants, in only four operations. Finally, this process could also be conducted in an enantioselective fashion, as demonstrated with the desymmetrization of naphthalene.