Rhodium-Catalyzed Asymmetric C-H Functionalization Reactions.

This review summarizes the advancements in rhodium-catalyzed asymmetric C-H functionalization reactions during the last two decades. Parallel to the rapidly developed palladium catalysis, rhodium catalysis has attracted extensive attention because of its unique reactivity and selectivity in asymmetric C-H functionalization reactions. In recent years, Rh-catalyzed asymmetric C-H functionalization reactions have been significantly developed in many respects, including catalyst design, reaction development, mechanistic investigation, and application in the synthesis of complex functional molecules. This review presents an explicit outline of catalysts and ligands, mechanism, the scope of coupling reagents, and applications.

Enantioselective Synthesis of N-N Biaryl Atropisomers through Iridium(I)-Catalyzed C-H Alkylation with Acrylates.

Enantioselective synthesis of N-N biaryl atropisomers is an emerging area but remains underexplored. The development of efficient synthesis of N-N biaryl atropisomers is in great demand. Herein, the construction of N-N biaryl atropisomers through iridium-catalyzed asymmetric C-H alkylation is reported for the first time. In the presence of readily available Ir precursor and Xyl-BINAP, a variety of axially chiral molecules based on indole-pyrrole skeleton were obtained in good yields (up to 98 %) with excellent enantioselectivity (up to 99 % ee). In addition, N-N bispyrrole atropisomers could also be synthesized in excellent yields and enantioselectivity. This method features perfect atom economy, wide substrate scope, and multifunctionalized products allowing diverse transformations.

Synthesis of Atropisomers by Transition-Metal-Catalyzed Asymmetric C-H Functionalization Reactions.

Transition-metal-catalyzed enantioselective C-H functionalization has become a powerful strategy for the formation of C-C or C-X bonds, enabling the highly asymmetric synthesis of a wide range of enantioenriched compounds. Atropisomers are widely found in natural products and pharmaceutically relevant molecules, and have also found applications as privileged frameworks for chiral ligands and catalysts. Thus, research into asymmetric routes for the synthesis of atropisomers has garnered great interest in recent years. In this regard, transition-metal-catalyzed enantioselective C-H functionalization has emerged as an atom-economic and efficient strategy toward their synthesis. In this Perspective, the approaches for the synthesis of atropisomers by transition-metal-catalyzed asymmetric C-H functionalization reactions are summarized. The main focus here is on asymmetric catalysis via Pd, Rh, and Ir complexes, which have been the most frequently utilized catalysts among reported enantioselective C-H functionalization reactions. Finally, we discuss limitations on available protocols and give an outlook on possible future avenues of research.

CpxM(iii)-catalyzed enantioselective C-H functionalization through migratory insertion of metal-carbenes/nitrenes.

CpxM(iii)-catalyzed enantioselective C-H functionalization reactions have progressed rapidly using either chiral cyclopentadienyl ligands or appropriate chiral carboxylic acids. In this context, highly reactive carbene and nitrene precursors can serve as effective C-H coupling partners, providing a straightforward and efficient approach to access chiral molecules. In this review, we highlight the developments in CpxM(iii)-catalyzed enantioselective C-H functionalization reactions through migratory insertion of metal-carbenes/nitrenes by employing chiral CpxM(iii) complexes or achiral CpxM(iii) complexes combined with chiral carboxylic acids.

Oxygen-Linked Cyclopentadienyl Rhodium(III) Complexes-Catalyzed Asymmetric C-H Arylation of Benzo[h]quinolines with 1-Diazonaphthoquinones.

Chiral cyclopentadienyl rhodium (CpRh) complex-catalyzed asymmetric C-H functionalization reactions have witnessed a significant progress in organic synthesis. In sharp contrast, the reported chiral Cp ligands are limited to C-linked Cp and are often synthetically challenging. To address these issues, we have developed a novel class of tunable chiral cyclopentadienyl ligands bearing oxygen linkers, which were efficient catalysts for C-H arylation of benzo[h]quinolines with 1-diazonaphthoquinones, affording axially chiral heterobiaryls in excellent yields and enantioselectivity (up to 99 % yield, 98.5:1.5 er). Mechanistic studies suggest that the reaction is likely to proceed by electrophilic C-H activation, and followed by coupling of the cyclometalated rhodium(III) complex with 1-diazonaphthoquinones.

SCpRh(III)-Catalyzed Enantioselective Synthesis of Atropisomers by C2-Arylation of Indoles with 1-Diazonaphthoquinones.

The Rh(III)-catalyzed highly enantioselective C2-arylation of indole derivatives with 1-diazonaphthoquinones is reported. In the presence of 2.5 mol % SCpRh complex and 20 mol % AgNO3, the C2-arylation reactions of indoles proceeded smoothly, affording a wide range of C2-arylated indole atropisomers in good yields and enantioselectivity (≤96% yield, ≤97% ee) under mild conditions. The method displays a broad substrate scope and good functional group tolerance.