Stereocontrol of C–N Axial and Spiro-Central Chirality via Rh(II)-Catalyzed Enantioselective N–H Bond Insertion of Indolinone-Spiroacetal
Qiao Ren, Ming Lang, Haitao Liu, Xiangyu Li, Daoshun Wu, Jiayun Wu, Meihua Yang, Jianhe Wei, Zhi Ren, Lei Wang
Abstract
A rhodium-catalyzed carbene N–H insertion protocol for simultaneously controlling the C–N axial and spiro-central 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.
Topics & Concepts
Enantiopure drugChemistryEnantioselective synthesisChirality (physics)Axial chiralityRhodiumStereochemistryCarbeneCatalysisOrganic chemistryPhysicsQuantum mechanicsQuarkChiral symmetry breakingNambu–Jona-Lasinio modelAxial and Atropisomeric Chirality SynthesisCyclopropane Reaction MechanismsCatalytic C–H Functionalization Methods