Molecular Ring Remodeling through C–C Bond Cleavage DOI
Zengrui Cheng, Zhibin Hu, Ning Jiao

et al.

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

Published: Feb. 27, 2025

ConspectusStable and inert C-C bonds form the fundamental framework of organic compounds. Consequently, direct transformations involving bond cleavage present an innovative approach for rapid modification remodeling molecular skeletons. In recent years, concept skeletal editing has garnered widespread attention been significantly developed, providing new opportunities late-stage bioactive molecules, high-value transformation bulk chemicals, a revolution in traditional fragment coupling strategies chemical synthesis. Notable advancements this field have focused on cyclic including ring expansion, contraction, ring-opening reactions, thereby enriching synthetic toolbox available to chemists. However, selective remains formidable challenge, especially complex due high dissociation energy difficulty achieving precise selectivity control. Over past few our group made efforts address these challenges. We demonstrated potential molecule reactions as efficient strategy synthesis molecules.Herein, we two major thematic achieved by group, utilizing cascade activation entropy-driven reconstruction via cleavage. These are characterized mild conditions, accessibility catalysts reagents, exceptional functional compatibility, emerging novel approaches through atom-incorporation mainly nitrogenation, oxygenation, halogenation synthesize pharmaceuticals, natural products, material molecules. (1) Ring expansion reactions: developed that enable insertion C-, N-, O-containing units into rings. methodologies offer practical routes synthesizing amides, amines, lactones, nitrogen-containing heterocycles. (2) Ring-opening enables construction distally difunctionalized frameworks. By transition metal catalysis radical-mediated process, successfully both single C═C double within Furthermore, tackled highly challenging arene (ARO) reaction, enabling stereoselective conjugated systems unsaturation liberation aromatic systems. Mechanistic studies DFT calculations provided critical insights processes. also identified key intermediates involved cleavage, benzyl azide, O-acetyl hydroxylamine, β-azido peroxyl radical, copper bisnitrene, 2-nitrene indazole. findings deepened understanding mechanisms strategy, which further promoted discovery related acyclic substrates.

Language: Английский

Selective nitrogen insertion into aryl alkanes DOI Creative Commons

Zheng Zhang,

Decheng Li, Zengrui Cheng

et al.

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

Published: July 17, 2024

Abstract Molecular structure-editing through nitrogen insertion offers more efficient and ingenious pathways for the synthesis of nitrogen-containing compounds, which could benefit development synthetic chemistry, pharmaceutical research, materials science. Substituted amines, especially alkyl heterocyclic are widely found in nature products drugs. Generally, accessing these compounds requires multiple steps, result low efficiency. In this work, a molecular editing strategy is used to realize using aryl alkanes as starting materials. Using derivatives O -tosylhydroxylamine source, method enables precise into C sp 2 -C 3 bond alkanes. Notably, further applications demonstrate that be prepare bioactive molecules with good efficiency modify skeleton Furthermore, plausible reaction mechanism involving transformation carbocation imine intermediates has been proposed based on results control experiments.

Language: Английский

Citations

7
Copper‐Catalyzed Aromatization‐Driven Ring‐Opening Amination and Oxygenation of Spiro Dihydroquinazolinones DOI Open Access
Wenke Li,

Hong-Jie Miao,

Jinhua Zhang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(58)

Published: Aug. 8, 2024

Abstract Mild and inexpensive copper‐catalyzed aromatization‐driven ring‐opening amination oxygenation of spiro dihydroquinazolinones are presented, respectively. These protocols provide facile atom‐economical access to the aminated carbonyl‐containing quinazolin‐4(3 H )‐ones in good yields with functional group compatibility, which difficult obtain by conventional methods. Remarkably, a telescoped procedure involving condensation ring‐opening/functionalization for simple cycloalkanone was found be accessible. Mechanistic studies suggest radical pathway this transformation.

Language: Английский

Citations

3
Molecular Ring Remodeling through C–C Bond Cleavage DOI
Zengrui Cheng, Zhibin Hu, Ning Jiao

et al.

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

Published: Feb. 27, 2025

ConspectusStable and inert C-C bonds form the fundamental framework of organic compounds. Consequently, direct transformations involving bond cleavage present an innovative approach for rapid modification remodeling molecular skeletons. In recent years, concept skeletal editing has garnered widespread attention been significantly developed, providing new opportunities late-stage bioactive molecules, high-value transformation bulk chemicals, a revolution in traditional fragment coupling strategies chemical synthesis. Notable advancements this field have focused on cyclic including ring expansion, contraction, ring-opening reactions, thereby enriching synthetic toolbox available to chemists. However, selective remains formidable challenge, especially complex due high dissociation energy difficulty achieving precise selectivity control. Over past few our group made efforts address these challenges. We demonstrated potential molecule reactions as efficient strategy synthesis molecules.Herein, we two major thematic achieved by group, utilizing cascade activation entropy-driven reconstruction via cleavage. These are characterized mild conditions, accessibility catalysts reagents, exceptional functional compatibility, emerging novel approaches through atom-incorporation mainly nitrogenation, oxygenation, halogenation synthesize pharmaceuticals, natural products, material molecules. (1) Ring expansion reactions: developed that enable insertion C-, N-, O-containing units into rings. methodologies offer practical routes synthesizing amides, amines, lactones, nitrogen-containing heterocycles. (2) Ring-opening enables construction distally difunctionalized frameworks. By transition metal catalysis radical-mediated process, successfully both single C═C double within Furthermore, tackled highly challenging arene (ARO) reaction, enabling stereoselective conjugated systems unsaturation liberation aromatic systems. Mechanistic studies DFT calculations provided critical insights processes. also identified key intermediates involved cleavage, benzyl azide, O-acetyl hydroxylamine, β-azido peroxyl radical, copper bisnitrene, 2-nitrene indazole. findings deepened understanding mechanisms strategy, which further promoted discovery related acyclic substrates.

Language: Английский

Citations

0