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Enantioselective Synthesis of Axially Chiral Benzothiophene/Benzofuran‐Fused Biaryls by N‐Heterocyclic Carbene Catalyzed Arene Formation
Author(s) -
Zhang ChunLin,
Gao YuanYuan,
Wang HaiYing,
Zhou BangAn,
Ye Song
Publication year - 2021
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.202103415
Subject(s) - benzofuran , benzothiophene , enantioselective synthesis , atropisomer , axial chirality , carbene , chemistry , annulation , catalysis , combinatorial chemistry , organic chemistry , stereochemistry , thiophene
Axially chiral biaryl scaffolds are prevalent in natural products, chiral ligands, and organocatalysts. However, N‐heterocyclic carbene (NHC) catalyzed de novo construction of an aromatic ring with concomitant axial chirality induction for the synthesis of biaryl atropisomers is far less developed, and the efficient synthesis of axially chiral tetra‐ ortho ‐substituted biaryls remains an unsolved problem under NHC catalysis. Reported here is an NHC‐catalyzed de novo synthesis of axially chiral benzothiophene/benzofuran‐fused biaryls from enals and 2‐benzyl‐benzothiophene/benzofuran‐3‐carbaldehydes through a [2+4] annulation, decarboxylation, and oxidative aromatization cascade with central‐to‐axial chirality conversion. The developed method provides efficient and general access to novel axially chiral benzothiophene/benzofuran‐fused biaryls in high enantioselectivities and works well for the synthesis of tetra‐ ortho ‐substituted biaryls.