Enantioselective Synthesis of Axially Chiral Benzothiophene/Benzofuran‐Fused Biaryls by N‐Heterocyclic Carbene Catalyzed Arene Formation. (12th May 2021)

• Record Type: Journal Article
• Authors: Zhang, Chun‐Lin; Gao, Yuan‐Yuan; Wang, Hai‐Ying; Zhou, Bang‐An; Ye, Song
• Is Part Of: Angewandte Chemie. Volume 133:Number 25(2021)
• Page Start: 14037
• Page End: 14041
• Publication Date: 2021-05-12
• Subjects: arenes -- atropisomerism -- chirality -- N-heterocyclic carbenes -- organocatalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202103415
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: 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. Abstract : The N‐heterocyclic carbene catalyzed enantioselective de novo synthesis of axially chiral benzothiophene/benzofuran‐fused biaryls from enals and 2‐benzylbenzothiophene/benzofuran‐3‐carbaldehydes has been developed. This cascade process comprises a [2+4] annulation, decarboxylation, and oxidative aromatization with central‐to‐axial chirality conversion, allowing rapid access to atropoisomeric tri‐ and tetra‐ ortho ‐substituted biaryls with high enantioselectivities.