Atroposelective Synthesis of Pyridoindolones Bearing Two Remote Distinct C–N Axes through Cobalt-Catalyzed Enantioselective C–H Activation

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

C–N axially chiral compounds represent an important class of atropisomers that are prevalent in bioactive and material molecules. Despite recent advances synthetic methodologies, the asymmetric construction featuring multiple axes has been rarely explored, significantly limiting their further applications. Herein, we report a novel atroposelective synthesis diaxially pyridoindolones both six–five six–six through cobalt-catalyzed C–H annulation. This approach demonstrates exceptional efficiency, yielding diverse array with excellent yields atroposelectivities (60 examples, up to >99% yield, ee, >20:1 dr). Mechanistic studies revealed stereochemistry were generated fixed simultaneously during cyclometalation step, along unexpected amplification effect. The practicality this protocol is underscored by successful gram-scale syntheses various transformations, including formation phosphine ligand. Notably, photoluminescence quantum (ΦF 0.99) positive solvatochromism observed, coupled significant chiroptical properties, underscoring potential applications these organic fluorescent materials.

Язык: Английский

Synthesis of Axially Chiral Compounds via Transition Metal-Catalyzed Atroposelective C–H Functionalization

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Апрель 14, 2025

ConspectusAxially chiral skeletons are prevalent in natural products and biologically important compounds, they widely utilized as privileged scaffolds enantioselective catalysis. Consequently, the catalytic atroposelective synthesis of enantiopure atropisomers has garnered considerable attention. A variety synthetic strategies involving metal catalysis or organocatalysis have been developed. Among these elegant approaches, transition metal-catalyzed C-H activation emerged an atom- step-economical strategy to streamline construction axially compounds recent years.In this Account, we discuss our efforts different types including biaryls, atropisomeric styrenes, C-N atropisomers, via strategies. To end, developed several transient directing group (cTDG) using Pd(OAc)2 tert-leucine (Tle), well systems Pd(II)/chiral phosphoric acid (CPA), Pd(II)/l-pyroglutamic (pGlu), Pd(0)/norbornene cooperative with a biimidazoline (BiIM) ligand, Co(II)/salicyloxazoline (Salox).At outset, successfully applied cTDG access biaryl aldehydes through Pd-catalyzed olefination, alkynylation, allylation, naphthylation, alkylation. The efficacy methods demonstrated aldehyde catalysts products, such TAN-1085, (+)-isochizandrin, (+)-steganone. facilitate diverse functionalities, novel Pd(II)/CPA system, which enables preparation various quinolines, biaryl-2-amines, biaryls bearing chalcogenoether units high enantioselectivities. system also allows for more challenging conjugated diene-based styrenes.Nonbiaryl styrenes anilides, present challenges due their conformational instability higher degree rotational freedom compared counterparts. We addressed achieved highly efficient anilides Pd(II)/pGlu Pd(0)/norbornene/BiIM In addition palladium catalysis, cobalt(II)/Salox vicinal C-C stereogenic axes, remote distinct diaxes, calix[4]arenes featuring both inherent axial chirality. anticipate that will find broad applications synthetically useful compounds.

Язык: Английский