Molecular Editing of Pyrroles via a Skeletal Recasting Strategy DOI Creative Commons
Xueting Zhou, Qingqin Huang, Jiami Guo

et al.

ACS Central Science, Journal Year: 2023, Volume and Issue: 9(9), P. 1758 - 1767

Published: Aug. 15, 2023

Heterocyclic scaffolds are commonly found in numerous biologically active molecules, therapeutic agents, and agrochemicals. To probe chemical space around heterocycles, many powerful molecular editing strategies have been devised. Versatile C-H functionalization allow for peripheral modifications of heterocyclic motifs, often being specific taking place at multiple sites. The past few years seen the quick emergence exciting "single-atom skeletal editing" strategies, through one-atom deletion or addition, enabling ring contraction/expansion structural diversification, as well scaffold hopping. construction heterocycles via deconstruction simple is unknown. Herein, we disclose a new method which name recasting strategy. Specifically, by tapping on 1,3-dipolar property azoalkenes, recast pyrroles to fully substituted pyrroles, phosphoric acid-promoted one-pot reaction consisting dearomative rearomative reconstruction steps. allows easy access synthetically challenging tetra-substituted otherwise difficult synthesize. Furthermore, construct N-N axial chirality our pyrrole products, accomplish facile synthesis anticancer drug, Sutent. potential application this other has also demonstrated.

Language: Английский

Single-atom logic for heterocycle editing DOI
Justin Jurczyk, Jisoo Woo, Sojung F. Kim

et al.

Nature Synthesis, Journal Year: 2022, Volume and Issue: 1(5), P. 352 - 364

Published: April 11, 2022

Language: Английский

Citations

288
Late-stage diversification of indole skeletons through nitrogen atom insertion DOI
Julia C. Reisenbauer, Ori Green, Allegra Franchino

et al.

Science, Journal Year: 2022, Volume and Issue: 377(6610), P. 1104 - 1109

Published: Sept. 1, 2022

Compared with peripheral late-stage transformations mainly focusing on carbon-hydrogen functionalizations, reliable strategies to directly edit the core skeleton of pharmaceutical lead compounds still remain scarce despite recent flurry activity in this area. Herein, we report skeletal editing indoles through nitrogen atom insertion, accessing corresponding quinazoline or quinoxaline bioisosteres by trapping an electrophilic nitrene species generated from ammonium carbamate and hypervalent iodine. This reactivity relies strategic use a silyl group as labile protecting that can facilitate subsequent product release. The utility highly functional group-compatible methodology context several commercial drugs is demonstrated.

Language: Английский

Citations

208
Skeletal Editing Approach to Bridge-Functionalized Bicyclo[1.1.1]pentanes from Azabicyclo[2.1.1]hexanes DOI
Brandon A. Wright, Anastassia Matviitsuk, Michael J. Black

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(20), P. 10960 - 10966

Published: May 5, 2023

Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) have emerged as attractive classes of sp3-rich cores for replacing flat, aromatic groups with metabolically resistant, three-dimensional frameworks in drug scaffolds. Strategies to directly convert, or "scaffold hop", between these bioisosteric subclasses through single-atom skeletal editing would enable efficient interpolation within this valuable chemical space. Herein, we describe a strategy hop" aza-BCH BCP nitrogen-deleting edit. Photochemical [2+2] cycloadditions, used prepare multifunctionalized frameworks, are coupled subsequent deamination step afford bridge-functionalized BCPs, which few synthetic solutions currently exist. The modular sequence provides access various privileged bridged bicycles pharmaceutical relevance.

Language: Английский

Citations

81
Recent Progress in Synthetic Applications of Hypervalent Iodine(III) Reagents DOI Creative Commons
Akira Yoshimura, Viktor V. Zhdankin

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 13, 2024

Hypervalent iodine(III) compounds have found wide application in modern organic chemistry as environmentally friendly reagents and catalysts. iodine are commonly used synthetically important halogenations, oxidations, aminations, heterocyclizations, various oxidative functionalizations of substrates. Iodonium salts arylating reagents, while iodonium ylides imides excellent carbene nitrene precursors. Various derivatives benziodoxoles, such azidobenziodoxoles, trifluoromethylbenziodoxoles, alkynylbenziodoxoles, alkenylbenziodoxoles group transfer the presence transition metal catalysts, under metal-free conditions, or using photocatalysts photoirradiation conditions. Development hypervalent catalytic systems discovery highly enantioselective reactions chiral represent a particularly recent achievement field chemistry. Chemical transformations promoted by many cases unique cannot be performed any other common, non-iodine-based reagent. This review covers literature published mainly last 7-8 years, between 2016 2024.

Language: Английский

Citations

33
Enantioselective synthesis of 2-substituted bicyclo[1.1.1]pentanes via sequential asymmetric imine addition of bicyclo[1.1.0]butanes and skeletal editing DOI

Jinteng Che,

Wei‐Yi Ding, Hongbo Zhang

et al.

Nature Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 28, 2025

Language: Английский

Citations

7
Molecular editing in natural product synthesis DOI

Chunngai Hui,

Zhuo Wang, Shiping Wang

et al.

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(5), P. 1451 - 1457

Published: Jan. 1, 2022

Molecular editing entailing insertion and deletion of atom(s) enables new synthetic design the efficiency natural product synthesis could be improved.

Language: Английский

Citations

54
syn-Selective Difunctionalization of Bicyclobutanes Enabled by Photoredox-Mediated C–S σ-Bond Scission DOI
Huamin Wang, Johannes E. Erchinger,

Madina Lenz

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(43), P. 23771 - 23780

Published: Oct. 18, 2023

Given the importance of cyclic frameworks in molecular scaffolds and drug discovery, it is intriguing to precisely forge manipulate ring systems synthetic chemistry. In this field, intermolecular synthesis densely substituted cyclobutanes with precise diastereocontrol under simple reaction conditions remains a challenge. Herein, photoredox strategy for difunctionalization bicyclo[1.1.0]butanes (BCBs) high regio- syn-selectivity disclosed. C-S σ-bond cleavage partially unsaturated sulfur-containing bifunctional reagents an overall strain-release-driven process enables thio-alkynylation, -alkenylation, -allylation BCBs mild demonstrates generality protocol. Mechanistic studies suggest that intermediacy distonic radical cations might be key efficient scission σ-bonds origin diastereoselectivity.

Language: Английский

Citations

39
Single-atom skeletal editing of 2H-indazoles enabled by difluorocarbene DOI
Yao Zhou,

F Chen,

Ziru Li

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(7), P. 1975 - 1981

Published: May 11, 2023

Language: Английский

Citations

29
Catalytic Enantioselective [3+2] Cycloaddition of N‐Metalated Azomethine Ylides DOI Creative Commons
Sundaravel Vivek Kumar, Patrick J. Guiry

Chemistry - A European Journal, Journal Year: 2023, Volume and Issue: 29(28)

Published: March 7, 2023

Abstract Asymmetric [3+2] cycloaddition reactions are fascinating and powerful methods for the synthesis of enantioenriched pyrrolidines up to four stereocentres. Pyrrolidines important compounds both biology organocatalytic applications. This review summarizes most recent advances in enantioselective by cycloadditions azomethine ylides using metal catalysis. It has been organized type catalysis used further arranged complexity nature dipolarophile. The presentation each reaction highlights their advantages limitations.

Language: Английский

Citations

28
Molecular Editing of Ketones through N-Heterocyclic Carbene and Photo Dual Catalysis DOI
Qing‐Zhu Li,

Mei-Hao He,

Rong Zeng

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22829 - 22839

Published: Aug. 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

Language: Английский

Citations

17