Stereocontrol of C–N Axial and Spiro-Central Chirality via Rh(II)-Catalyzed Enantioselective N–H Bond Insertion of Indolinone-Spiroacetal

Abstract

A rhodium-catalyzed carbene N−H insertion protocol for simultaneously controlling the C−N axial and spirocentral chiralities is disclosed, resulting in the rapid assembly of enantiopure N-arylindolinone-spiroacetal derivatives in high yields with excellent enantioselectivities. This promising strategy features the chiral C−N axis, spiro-central chirality, functional group tolerance, and late-stage diversification. DFT calculations indicate that the N−H insertion is the axial-chirality-determining step and that the 1,5-H shift step is regiospecifically caused by the spirocycle.

Intermolecular Buchwald–Hartwig Reactions for Enantioselective Synthesis of Diverse Atropisomers: Rerouting the C–N Forming Mechanism to Substrate Oxygen-Assisted Reductive Elimination

“…In contrast, the strategy of de novo construction of a C–N bond as a chiral axis, however, is dauntingly challenging, likely due to steric effects. These systems typically involve arylation of a bulky NH nucleophile using a highly reactive electrophile such as hypervalent iodine or a carbene reagent, which capitalized on the substrate activation strategy. Considering the sporadic examples of intermolecular coupling and coupling through de novo C–N axis formation, general protocols for accessing the atropisomeric forms of biaryl N–C atropisomers are in great demand, especially when using readily available reagents.…”