Nitrosobenzene‐Enabled Chiral Phosphoric Acid Catalyzed Enantioselective Construction of Atropisomeric N‐Arylbenzimidazoles

Abstract

Described herein is an imidazole ring formation strategy for the synthesis of axially chiral N-arylbenzimidazoles by means of chiral phosphoric acid catalysis. Two sets of conditions were developed to transform two classes of 2naphthylamine derivatives into structurally diverse N-arylbenzimidazole atropisomers with excellent chemo-and regioselectivity as well as high levels of enantiocontrol. It is worth reflecting on the unique roles played by the nitroso group in this domino reaction. It functions as a linchpin by first offering an electrophilic site (N) for the initial C À N bond formation while the resulting amine performs the nucleophilic addition to form the second CÀN bond. Additionally, it could facilitate the final oxidative aromatization as an oxidant. The atropisomeric products could be conveniently elaborated to a series of axially chiral derivatives, enabling the exploitation of N-arylbenzimidazoles for their potential utilities in asymmetric catalysis.

Atroposelective Synthesis of Heterobiaryls through Ring Formation

“…In 2021, Tan, Zhong, and co‐workers reported two kinds of CPA‐catalyzed asymmetric synthesis of axially chiral N ‐arylbenzimidazoles 92 a and 92 b via an imidazole ring formation strategy from 2‐naphthylamines 90 a or 90 b and nitrosobenzenes 91 (Scheme 30a) [53] . A series of N ‐arylbenzimidazole atropisomers can be easily prepared with excellent chemo‐, regio‐, and stereoselectivity (up to 97 % ee).…”

“… Synthesis of axially chiral N ‐arylbenzimidazoles of naphthylamine derivatives and nitrosobenzene [53] …”