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Chiral amine scaffolds are among the most important building blocks in natural products, drug molecules, and functional materials, which have prompted chemists to focus more on their synthesis. Among the accomplishments in chiral amine synthesis, transition-metal-catalyzed enantioselective C–N cross-coupling is considered one of the most efficient protocols. This approach combines traditional C(sp2)–N cross-coupling methods (such as the Buchwald–Hartwig reaction Ullmann-type reaction, and Chan–Evans–Lam reaction), aryliodonium salt chemistry and radical chemistry, providing an attractive pathway to a wide range of structurally diverse chiral amines with high enantioselectivity. This review summarizes the established protocols and offers a comprehensive outlook on the promising enantioselective C–N cross-coupling reaction. [ABSTRACT FROM AUTHOR]

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL‐derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C−N bond formation to afford N‐aryl quinone atropisomers with an unprecedented intramolecular N−H−O hydrogen bond within a six‐membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram‐scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition. [ABSTRACT FROM AUTHOR]

N−N Atropisomers are a common motif in natural products and represent a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the catalytic atroposelective synthesis of such molecules remains challenging, hampering meaningful development. In particular, an enantioselective synthesis of N−N bisindole atropisomers is unprecedented. Herein, the first enantioselective synthesis of N−N bisindole atropisomers via the palladium‐catalyzed de novo construction of one indole skeleton is presented. A wide variety of N−N axially chiral bisindoles were generated in good yields with excellent enantioselectivities via a cascade condensation/N‐arylation reaction. Structurally diverse indole‐pyrrole, indole‐carbazole, and non‐biaryl‐indole atropisomers possessing a chiral N−N axis were accessed using this protocol. Moreover, investigations using density functional theory (DFT) calculations provided insight into the reaction mechanism and enantiocontrol. [ABSTRACT FROM AUTHOR]

N−C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, the enantioselective synthesis of N−C biaryl atropisomers by stereoselective metal‐catalyzed aryl amination remains unprecedented. Herein, a Pd‐catalyzed cross‐coupling strategy is presented for the synthesis of N−C axially chiral biaryl molecules. A broad spectrum of N−C axially chiral compounds was obtained with excellent enantioselectivities (up to 99 % ee) and good yields (up to 98 %). The practicality of this reaction was validated in the synthesis of useful biological molecules. [ABSTRACT FROM AUTHOR]