Bioactive atropisomers: Unraveling design strategies and synthetic routes for drug discovery DOI
Shuai‐Jiang Liu,

Qian Zhao,

Xiaochen Liu

et al.

Medicinal Research Reviews, Journal Year: 2024, Volume and Issue: 44(5), P. 1971 - 2014

Published: March 21, 2024

Atropisomerism, an expression of axial chirality caused by limited bond rotation, is a prominent aspect within the field medicinal chemistry. It has been shown that atropisomers wide range compounds, including established FDA-approved drugs and experimental molecules, display markedly different biological activities. The time-dependent reversal in poses complexity obstacles process drug discovery development. Nonetheless, recent progress understanding atropisomerism enhanced characterization methods have greatly assisted chemists effective development atropisomeric molecules. This article provides comprehensive review their special design thoughts, synthetic routes, activities, serving as reference for synthesis evaluation bioactive future.

Language: Английский

Catalytic atroposelective synthesis DOI
Shao‐Hua Xiang, Wei‐Yi Ding, Yong‐Bin Wang

et al.

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(5), P. 483 - 498

Published: April 30, 2024

Language: Английский

Citations

39
Cobalt‐Catalyzed Enantioselective C−H Carbonylation towards Chiral Isoindolinones DOI

Ming‐Ya Teng,

Yong‐Jie Wu,

Jiahao Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(10)

Published: Jan. 11, 2024

Transition metal-catalyzed enantioselective C-H carbonylation with carbon monoxide, an essential and easily available C1 feedstock, remains challenging. Here, we disclosed unprecedented catalyzed by inexpensive readily cobalt(II) salt. The reactions proceed efficiently through desymmetrization, kinetic resolution, parallel affording a broad range of chiral isoindolinones in good yields excellent enantioselectivities (up to 92 % yield 99 ee). synthetic potential this method was demonstrated asymmetric synthesis biological active compounds, such as (S)-PD172938 (S)-Pazinaclone. resulting also serve ligands cobalt-catalyzed annulation alkynes construct phosphorus stereocenter.

Language: Английский

Citations

21
Cobalt(III)-Catalyzed Enantioselective C–H Functionalization: Ligand Innovation and Reaction Development DOI
Qi‐Jun Yao, Bing‐Feng Shi

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, environmentally friendly 3d metals poses substantial challenges, primarily due variable oxidation states, intricate coordination patterns, limited mechanistic insights. In this Account, we summarize our research endeavors in three types Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, situ-generated octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) Co(II)/chiral phosphoric (CPA) cooperative achieved through strategic ligand design. Our initial objective was achieve functionalization Cp*Co(III) catalysts with external ligands, aiming circumvent laborious preparation CpxCo(III) complexes. To end, developed several CCA incorporating non-covalent interactions (NCIs) a crucial design element. Next, address limitations associated lengthy synthesis Cp-ligated complexes difficulties modification, explored concept situ generation catalysis using commercially available cobalt(II) salts tailor-made ligands. This exploration led two innovative catalytic systems, namely, Co(II)/Salox Co(II)/CCA sequential catalysis. The emerged versatile strategy, demonstrating excellent enantioselectivities across range asymmetric reactions construct various molecules central, axial, planar, inherent chirality. facile single step, along ease further enhances versatility applicability approach. Moreover, successfully applied cobalt/Salox electro- photochemical-catalyzed functionalization, electrons or oxygen traceless oxidant, thereby eliminating need stoichiometric chemical oxidants. Through studies reaction developments, elucidated detailed structure-enantioselectivity relationships which are expected inform future endeavors. Finally, Co(II)/CPA enabled spiro-γ-lactams olefination/asymmetric [4 + 1] spirocyclization. Mechanistically, establishment stereochemistry occurs during cyclization where CPA serves both neutral Brønsted acid, stereoinduction independent cleavage step. We anticipate that insights advancements Account will inspire innovations drive progress metal-catalyzed reactions.

Language: Английский

Citations

4
Rhodium-Catalyzed Atroposelective C–H Alkylation of 1-Aryl Isoquinoline Derivatives with Cyclopropanols DOI
Wenwen Zhang, Quannan Wang, Chao Zheng

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4017 - 4024

Published: Feb. 20, 2025

Language: Английский

Citations

3
Atroposelective Synthesis of Pyridoindolones Bearing Two Remote Distinct C–N Axes through Cobalt-Catalyzed Enantioselective C–H Activation DOI
Pu‐Fan Qian, Yanxuan Wu,

Jia-Heng Hu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

3
Enantioselective C–H bond functionalization under Co(iii)-catalysis DOI

Bholanath Garai,

Abir Das,

Doppalapudi Vineet Kumar

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(25), P. 3354 - 3369

Published: Jan. 1, 2024

Enantioselective C–H functionalization relies on 4d and 5d metals, but with their depletion, sustainable alternatives using 3d metals are crucial.

Language: Английский

Citations

14
Enantioselective Rhodium‐Catalyzed C−H Arylation Enables Direct Synthesis of Atropisomeric Phosphines DOI
Zexian Li,

Weipeng Xu,

Shuaishuai Song

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(8)

Published: Jan. 6, 2024

Atropisomeric phosphines hold considerable significance in asymmetric catalysis, yet their synthesis presents a formidable challenge owing to intricate multistep procedures. In this context, groundbreaking methodology has been presented for preparation. This innovative approach entails an atroposelective rhodium-catalyzed C-H activation employing aryl and heteroaryl halides, chelated by P(III) center. The essence of strategy lies its ability directly construct chiral phosphine ligands single step, thereby exhibiting exceptional efficiency terms atom redox economy. Illustrative examples serve demonstrate the immense potential situ-formed catalysis. Mechanistic experiments have further provided invaluable insights into transformation.

Language: Английский

Citations

12
Asymmetric Dearomatization of Indoles through Cobalt‐Catalyzed Enantioselective C−H Functionalization Enabled by Photocatalysis DOI

Ming‐Ya Teng,

De‐Yang Liu,

Shiyu Mao

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: June 20, 2024

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger photocatalysis transition-metal-catalyzed asymmetric C-H activation as an efficient sustainable method for construction chiral molecules remains elusive challenging. Herein, we develop cobalt-catalyzed enantioselective enabled by visible-light photoredox catalysis, providing synergistic catalytic strategy dearomatization indoles with high levels enantioselectivity (96 % to >99 ee). Mechanistic studies indicate that excited photocatalyst was quenched divalent cobalt species presence Salox ligand, leading formation catalytically active Co(III) complex. Moreover, stoichiometric reactions cobaltacycle intermediate indole suggest irradiation visible light also play critical role step.

Language: Английский

Citations

10
Simultaneous construction of inherent and axial chirality by cobalt-catalyzed enantioselective C-H activation of calix[4]arenes DOI Creative Commons
Tong Li, Yanbo Zhang, Cong Du

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 3, 2024

Language: Английский

Citations

10
Palladium‐Catalyzed Atroposelective Kinetic C−H Olefination and Allylation for the Synthesis of C−B Axial Chirality DOI Open Access
Jie Xu, Weihua Qiu, Xu Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: Oct. 16, 2023

Abstract The direct C−H functionalization of 1,2‐benzazaborines, especially asymmetric version, remains a great challenge. Here we report palladium‐catalyzed enantioselective olefination and allylation reactions 1,2‐benzazaborines. This approach is kinetic resolution (KR), providing various C−B axially chiral 2‐aryl‐1,2‐benzazaborines 3‐substituted in generally high yields with excellent enantioselectivities (selectivity (S) factor up to 354). synthetic potential this reaction showcased by late‐stage modification complex molecules, scale‐up reaction, applications.

Language: Английский

Citations

17