Asymmetric Synthesis of N–N Axially Chiral Compounds by Phase-Transfer-Catalyzed Alkylations

Abstract

N–N axially chiral skeletons are significant structural motifs in natural products, pharmaceuticals, and functional materials. Herein we disclose a method for the asymmetric synthesis of N–N axially chiral compounds by phase-transfer catalysis. A wide range of N–N axially chiral quinazolinone derivatives were prepared in high yields with excellent stereoselectivities. Furthermore, the synthetic utility of the protocol was proved by large-scale reaction and transformation of the product. Density functional theory calculations provide insight into the mechanism.

Chiral Acid-Catalyzed Atroposelective Indolization Enables Access to 1,1′-Indole-Pyrroles and Bisindoles Bearing a Chiral N–N Axis

“…Only in the past two years, a dramatic surge of interest in this type of structure was documented (Scheme b) . In addition to the preparation of N,N-axially chiral monoheteroaryl compounds reported by the Lu group and the Li group, the Liu group, the Shi group, and our group introduced atroposelective synthesis of chiral N,N-bispyrroles by either enantioselective pyrrole substitution or pyrrole construction by the Paal-Knorr approach . Notably in our report, we further demonstrated our initial investigation on the application of functionalized bispyrroles as a chiral Brønsted acid catalyst .…”

Chiral phosphoric acid-catalyzed dual-ring formation for enantioselective construction of N–N axially chiral 3,3′-bisquinazolinones

“…9 Li's group further employed this strategy to construct N–N axially chiral quinazolinone derivatives. 10 Meanwhile, Liu and Lu's group utilized the desymmetrization strategy to enantioselectively synthesize N–N axially chiral bispyrroles (Scheme 1c). 11 In 2022, Shi's group further developed a chiral phosphoric acid-catalyzed ring formation synthesis to obtain optical N -pyrrolylindoles.…”

Cu(I)-Catalyzed Asymmetric Arylation of Pyrroles with Diaryliodonium Salts toward the Synthesis of N–N Atropisomers

“…The first catalytic asymmetric synthesis of N–N atropisomers was recently established by Lu, Houk, and their co-workers and our group . Very recently, the groups of Li, Shi, and Zhao also independently reported several syntheses of N–N atropisomers via asymmetric organocatalysis. Because of our continuing interest in the synthesis of atropisomers, we postulated that prochiral bipyrroles could serve as a platform for sp 3 –sp 2 C–C bond construction via an enantioselective C–H bond arylation approach .…”