Synthesis of Remote C–N Diaxially Chiral Compounds via Cobalt-Catalyzed Atroposelective C–H Activation DOI
Yanbo Zhang, Chen Yang,

Xindong Meng

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: June 4, 2025

The construction of atropisomers bearing multiple stereogenic elements has attracted considerable interest, given their broad utility in asymmetric catalysis, pharmaceuticas, and functional materials. Herein, we report a highly efficient cobalt-catalyzed atroposelective C-H activation-annulation reaction that simultaneously establishes two remote C-N chiral axes single operation. This approach proceeds under oxygen conditions by using commercially available cobalt(II) catalyst conjunction with salicyloxazoline (Salox) ligand. A wide range benzamides indole-based alkynes various groups are well tolerated, yielding desired products good yields high level enantio- diastereoselectivities. resulting diaxially demonstrate exceptional configurational stability at both axes. synthetic practicality is further highlighted scalable synthesis, versatile derivatizations, remarkable optical performance the target molecules.

Language: Английский

Asymmetric Intramolecular Hydroamination to Construct Diverse N–N/C–N Indole Atropisomers via Cooperative Pd(0) and Chiral Phosphoric Acid Catalysis DOI
Zhi Chen,

Xiaojun Wang,

Fu Pi

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Here we present an enantioselective intramolecular hydroamination reaction of o-aminophenyl-1,3-enynes via cooperative catalysis Pd(0) and chiral phosphoric acid. This approach enables the efficient construction N–N/C–N axially stereogenic indoles with broad skeletal diversity high levels enantioselectivity in a completely atom-economic manner. Mechanistic studies indicate that protonation alkyne moiety π-Lewis base activation is favored, phosphate counteranion plays crucial role controlling atroposelectivity ring-closure step.

Language: Английский

Citations

1
Development of Eagle‐Shaped BPE/Phe‐2NO Ligands: Switch of Enantioselectivity in Friedel–Crafts Alkylation DOI
Jun Young Yang,

Jing Lou,

Wei Li

et al.

Chemistry - An Asian Journal, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Abstract The development of single chiral source‐derived ligands to fine‐switch enantioselectivity has been a key aspect in asymmetric catalysis. Herein, this study, using the same source l ‐prolinamide as starting material, we synthesize 14 new diphenyl ether bridged C 2 ‐symmetric rigid tertiary amine‐derived dioxide (abberviated BPE‐2NO) and 9 m ‐phenylene Phe‐2NO); their effectiveness was demonstrated first switch palladium(II)‐catalyzed Friedel–Crafts alkylation. In presence palladium acetate Lewis acid, both enantiomers indole derivatives can be prepared good‐to‐excellent yields enantioselectivities by Eagle‐shaped BPE/Phe‐2NO ligands. Control experiments density functional theory calculations provide rational explanation for above observations. This study alkylation

Language: Английский

Citations

0
Recent Advances in Catalytic Atroposelective Synthesis of Axially Chiral Quinazolinones DOI Open Access
Yilin Liu, Jiaoxue Wang, Yanli Yin

et al.

Catalysts, Journal Year: 2025, Volume and Issue: 15(5), P. 426 - 426

Published: April 27, 2025

Quinazolinones, a class of nitrogen-containing heterocyclic compounds, occupy crucial position in medicinal chemistry and materials science due to their significant application potential. In recent years, the catalytic asymmetric synthesis axially chiral quinazolinones has emerged as prominent research area, driven by prospective applications development bioactive molecules, design ligands, fabrication functional materials. This review comprehensively summarizes advancements quinazolinones, with particular focus on construction strategies for three major structural types: C–N axis, N–N C–C axis. Key synthetic methodologies, including atroposelective halogenation, kinetic resolution, condensation–oxidation, photoredox deracemization, are discussed detail. addition, provides an in-depth analysis various systems, such peptide catalysis, enzymatic metal phosphoric acid others. Despite substantial progress made thus far, several challenges remain, expansion substrate scope, enhanced control over stereoselectivity, further exploration practical applications, drug discovery catalysis. These insights expected guide future towards novel strategies, diversification variants, comprehensive understanding biological activities functions. Ultimately, this will foster continued growth evolution rapidly advancing field.

Language: Английский

Citations

0
Catalytic Atroposelective aza-Grob Fragmentation: An Approach toward Axially Chiral Biarylnitriles DOI
Lin Li,

Linlin Ding,

Xue Zhang

et al.

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

Published: May 6, 2025

Grob fragmentation is a powerful synthetic tool for cleaving C-C bonds, which was particularly useful in the construction of seven- to nine-membered carbocycles or heterocycles. This reaction typically breaks one bond and C-X forms two unsaturated functional groups. As no stereogenic centers are generated, catalytic asymmetric has remained unexplored. In this study, we have successfully developed aza-Grob α-keto oxime esters, achieving atroposelective cleavage construct axially chiral biarylnitriles. Single-crystal X-ray diffraction analysis esters elucidated structure-reactivity relationship, highlighting role torsional strain. These studies also revealed unique 2-phenyl benzoyl group controlling substrate conformation, tuning reactivity, stereoselectivity. The 1H NMR titration experiments provided brief insights into activation mode catalyst with substrate, suggesting multi-hydrogen-bonding interaction model.

Language: Английский

Citations

0
Remote Copper-Catalyzed Atroposelective Synthesis of N–N Axially Chiral Compounds Bearing Minimally Different Alkyl Groups DOI

Zhaoliang Ge,

Cuiju Zhu,

Guang Xu

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: May 25, 2025

Herein, we report a copper-catalyzed remote asymmetric [4+1] annulation/aromatization between yne-allylic esters and N-aminoindoles, providing axially chiral N,N'-indolepyrroles that contain sterically comparable ortho substituents, such as methyl ethyl. This reaction proceeds smoothly under mild conditions, affording products with excellent regio- enantioselectivities while demonstrating broad functional group compatibility. The synthetic utility of this approach is further showcased through the late-stage modification biologically relevant scaffolds. Additionally, preliminary mechanistic investigations indicate nucleophilic substitution enantio-determining step.

Language: Английский

Citations

0
Synthesis of Remote C–N Diaxially Chiral Compounds via Cobalt-Catalyzed Atroposelective C–H Activation DOI
Yanbo Zhang, Chen Yang,

Xindong Meng

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: June 4, 2025

The construction of atropisomers bearing multiple stereogenic elements has attracted considerable interest, given their broad utility in asymmetric catalysis, pharmaceuticas, and functional materials. Herein, we report a highly efficient cobalt-catalyzed atroposelective C-H activation-annulation reaction that simultaneously establishes two remote C-N chiral axes single operation. This approach proceeds under oxygen conditions by using commercially available cobalt(II) catalyst conjunction with salicyloxazoline (Salox) ligand. A wide range benzamides indole-based alkynes various groups are well tolerated, yielding desired products good yields high level enantio- diastereoselectivities. resulting diaxially demonstrate exceptional configurational stability at both axes. synthetic practicality is further highlighted scalable synthesis, versatile derivatizations, remarkable optical performance the target molecules.

Language: Английский

Citations

0