Enantioselective Synthesis of Axially Chiral Benzothiophene/Benzofuran-Fused Biaryls by N-Heterocyclic Carbene Catalyzed Arene Formation

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.

Automated summary

An NHC-catalyzed de novo synthesis method for axially chiral benzothiophene/benzofuran-fused biaryls has been reported, providing a convenient and efficient access to these compounds with high enantioselectivities. The method also works well for the synthesis of tetra-ortho-substituted biaryls, addressing an unsolved problem in the field.