Enantioselective Synthesis of Axially Chiral Diaryl Ethers via NHC Catalyzed Desymmetrization and Following Resolution DOI Open Access

Bang‐An Zhou,

Xuening Li, Chunlin Zhang

и другие.

Angewandte Chemie, Год журнала: 2023, Номер 136(4)

Опубликована: Ноя. 29, 2023

Abstract Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access ether atropisomers. Herein, we report the N‐heterocyclic carbene‐catalyzed synthesis of axially via desymmetrization prochiral 2‐aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, heteroaromatic amines. This reaction features mild conditions, good functional group tolerance, broad substrate scope excellent enantioselectivity. The utility this methodology is illustrated by late‐stage functionalization, gram‐scale synthesis, diverse enantioretentive transformations. Control experiments DFT calculations support association NHC‐catalyzed following kinetic resolution enhance

Язык: Английский

Rational Molecular Editing: A New Paradigm in Drug Discovery DOI Creative Commons
Chunhua Ma, Craig W. Lindsley, Junbiao Chang

и другие.

Journal of Medicinal Chemistry, Год журнала: 2024, Номер 67(14), С. 11459 - 11466

Опубликована: Июнь 21, 2024

ADVERTISEMENT RETURN TO ARTICLES ASAPPREVEditorialNEXTRational Molecular Editing: A New Paradigm in Drug DiscoveryChunhua MaChunhua MaState Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, NMPA for Research and Evaluation Innovative Drug, School Chemistry Chemical Engineering, Henan Normal University, Xinxiang, 453007, ChinaMore by Chunhua Mahttps://orcid.org/0000-0001-7613-6471, Craig W. Lindsley*Craig LindsleyVanderbilt University Medical Center, Franklin, Tennessee 37027, United States*E-mail: [email protected]More Lindsleyhttps://orcid.org/0000-0003-0168-1445, Junbiao Chang*Junbiao ChangCollege Chemistry, State Zhengzhou 450001, China*E-mail: Chang, Bin Yu*Bin YuCollege Yuhttps://orcid.org/0000-0002-7207-643XCite this: J. Med. Chem. 2024, XXXX, XXX, XXX-XXXPublication Date (Web):June 21, 2024Publication History Received13 June 2024Published online21 2024https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c01347https://doi.org/10.1021/acs.jmedchem.4c01347editorialACS PublicationsPublished 2024 American Society. This publication is available under these Terms Use. Request reuse permissions free to access through this site. Learn MoreArticle Views-Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum full text article downloads since November 2008 (both PDF HTML) across all institutions individuals. These metrics regularly updated reflect usage leading up last few days.Citations number other articles citing article, calculated Crossref daily. Find more information about citation counts.The Altmetric Attention Score a quantitative measure attention that research has received online. Clicking on donut icon will load page at altmetric.com with additional details score social media presence given article. how calculated. Share Add toView InAdd Full Text ReferenceAdd Description ExportRISCitationCitation abstractCitation referencesMore Options onFacebookTwitterWechatLinked InRedditEmail (2 MB) Get e-AlertscloseSUBJECTS:Drug discovery,Macrocyclization,Molecules,Pharmaceuticals,Scaffolds e-Alerts

Язык: Английский

Процитировано

20
Enantioselective Synthesis of C−O Axially Chiral Diaryl Ethers by NHC‐Catalyzed Atroposelective Desymmetrization** DOI
Sayan Shee,

Sowmya Shree Ranganathappa,

Mahesh S. Gadhave

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(52)

Опубликована: Ноя. 21, 2023

Axially chiral diaryl ethers, a distinguished class of atropisomers possessing unique dual C-O axis, hold immense potential for diverse research domains. In contrast to the catalytic enantioselective synthesis conventional single axis bearing atropisomers, atroposelective axially ethers containing flexible remains significant challenge. Herein, we demonstrate first N-heterocyclic carbene (NHC)-catalyzed via esterification dialdehyde-containing ethers. Mechanistically, reaction proceeds NHC-catalyzed desymmetrization strategy afford corresponding ether in good yields and high enantioselectivities under mild conditions. The derivatization synthesized product expands utility present access library compounds. temperature dependency preliminary investigations on racemization barrier bonds are also presented.

Язык: Английский

Процитировано

39
Molecular medicinal insights into scaffold hopping-based drug discovery success DOI
Ayan Acharya, Mukul Yadav, Mithilesh Nagpure

и другие.

Drug Discovery Today, Год журнала: 2023, Номер 29(1), С. 103845 - 103845

Опубликована: Ноя. 26, 2023

Язык: Английский

Процитировано

26
Enantioselective Synthesis of Axially Chiral Diaryl Ethers via NHC Catalyzed Desymmetrization and Following Resolution DOI Open Access

Bang‐An Zhou,

Xuening Li, Chunlin Zhang

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(4)

Опубликована: Ноя. 29, 2023

Axially chiral diaryl ethers are present in numerous natural products and bioactive molecules. However, only few catalytic enantioselective approaches have been established to access ether atropisomers. Herein, we report the N-heterocyclic carbene-catalyzed synthesis of axially via desymmetrization prochiral 2-aryloxyisophthalaldehydes with aliphatic alcohols, phenol derivatives, heteroaromatic amines. This reaction features mild conditions, good functional group tolerance, broad substrate scope excellent enantioselectivity. The utility this methodology is illustrated by late-stage functionalization, gram-scale synthesis, diverse enantioretentive transformations. Control experiments DFT calculations support association NHC-catalyzed following kinetic resolution enhance

Язык: Английский

Процитировано

23
Photocatalytic furan-to-pyrrole conversion DOI

D.B. Kim,

Jaehyun You,

D. H. Lee

и другие.

Science, Год журнала: 2024, Номер 386(6717), С. 99 - 105

Опубликована: Окт. 3, 2024

The identity of a heteroatom within an aromatic ring influences the chemical properties that heterocyclic compound. Systematically evaluating effect single atom, however, poses synthetic challenges, primarily as result thermodynamic mismatches in atomic exchange processes. We present photocatalytic strategy swaps oxygen atom furan with nitrogen group, directly converting into pyrrole analog intermolecular reaction. High compatibility was observed various derivatives and nucleophiles commonly used drug discovery, late-stage functionalization furnished otherwise difficult-to-access pyrroles from naturally occurring furans high molecular complexity. Mechanistic analysis suggested polarity inversion through electron transfer initiates redox-neutral processes at room temperature.

Язык: Английский

Процитировано

14
Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis DOI
Qing‐Zhu Li,

Mei-Hao He,

Rong Zeng

и другие.

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(32), С. 22829 - 22839

Опубликована: Авг. 1, 2024

The molecular editing of ketones represents an appealing strategy due to its ability maximize the structural diversity ketone compounds in a straightforward manner. However, developing efficient methods for arbitrary modification ketonic molecules, particularly those integrated within complex skeletons, remains significant challenge. Herein, we present unique recasting that involves radical acylation

Язык: Английский

Процитировано

13
Silver-Promoted Three-Component Synthesis of Perfluoroalkenyl Pyrroles through Partial Defluorinative Functionalization of Perfluoroalkyl Halides DOI
Wenjun Ji, Wei Han,

Yuanyuan Ren

и другие.

Organic Letters, Год журнала: 2024, Номер 26(29), С. 6197 - 6202

Опубликована: Июль 15, 2024

A silver-promoted three-component heterocyclization of alkynes, perfluoroalkyl halides, and 1,3-dinucleophiles was developed for the efficient synthesis privileged (E)-perfluoroalkenyl pyrroles. The reaction proceeded through a rationally designed sequence radical perfluoroalkylation intramolecular defluorinative [3 + 2]-heterocyclization. utility halide as perfluoroalkenyl reagent, by selective controllable functionalization two inert C(sp3)–F bonds at vicinal carbon centers on chain, provides new mode value-added organofluorides starting from easily available low-cost fluorinated feedstock.

Язык: Английский

Процитировано

11
Precision single-atom editing: new frontiers in nitrogen insertion and substitution for the generation of N-heterocycles DOI

Xue Li,

Jia Xu, Zhigang Xu

и другие.

Organic Chemistry Frontiers, Год журнала: 2024, Номер 11(14), С. 4041 - 4053

Опубликована: Янв. 1, 2024

This paper primarily focuses on the editing of nitrogen atoms, encompassing insertion N, substitution C with and utilization 15 N in place 14 for construction N-heterocycles.

Язык: Английский

Процитировано

10
Toward the Generation of 2-Amino-3-Formyl Difunctionalized Chromones via Pd-Enabled Rearrangement Strategy DOI

Qi Tong,

Ren-Feng Xiu,

Jiahe Chen

и другие.

ACS Catalysis, Год журнала: 2023, Номер 13(19), С. 12692 - 12699

Опубликована: Сен. 14, 2023

Accomplished herein is a rearrangement strategy for the highly efficient assembly of synthetically cumbersome while medicinally significant 2-amino-3-formyl chromones via palladium-catalyzed ring-opening, rearrangement, and cyclization process. Such sequence enables formation one C(sp2)–O bond C(sp2)–C(sp2) bond, reconstruction benzo-γ-pyrone moiety in single operation, thus producing difunctionalized chromone-incorporated derivatives. The reaction proceeds shorter time (30 min 3-iodochromones most cases) atom- step-economical manner. synthetic application current protocol further demonstrated by late-stage modification pharmaceuticals their intermediates, gram-scale reactions, transformations functional groups, as well synthesis bioactive molecules drugs. Mechanistic studies indicate that nucleophilic ring-opening process moiety, phenoxy anion intermediate, an intramolecular might be involved present system.

Язык: Английский

Процитировано

21
Copper-catalyzed atroposelective synthesis of C–O axially chiral compounds enabled by chiral 1,8-naphthyridine based ligands DOI Creative Commons
Lei Dai, Xueting Zhou, Jiami Guo

и другие.

Chemical Science, Год журнала: 2024, Номер 15(16), С. 5993 - 6001

Опубликована: Янв. 1, 2024

Axially chiral molecular scaffolds are widely present in therapeutic agents, natural products, catalysts, and advanced materials. The construction of such molecules has garnered significant attention from academia industry. catalytic asymmetric synthesis axially biaryls, along with other non-biaryl molecules, been extensively explored the past decade. However, atroposelective C-O axial chirality remains largely underdeveloped. Herein, we document a copper-catalyzed compounds using novel 1,8-naphthyridine-based ligands. Mechanistic investigations have provided good evidence support mechanism involving synergistic interplay between desymmetrization reaction kinetic resolution process. method described this study holds great significance for compounds, promising applications organic chemistry. utilization ligands copper catalysis is anticipated to find broad copper(i)-catalyzed azide-alkyne cycloadditions (CuAACs) beyond.

Язык: Английский

Процитировано

5