Synthesis of Axially Chiral Vinyl Halides via Cu(I)-Catalyzed Enantioselective Radical 1,2-Halofunctionalization of Terminal Alkynes DOI

Jun-Bin Tang,

Jun-Qian Bian,

Zhihan Zhang

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 15(1), P. 502 - 513

Published: Dec. 20, 2024

Organohalides are crucial in modern organic synthesis, thanks to their robust and versatile reactivity cross-coupling other key transformations. However, catalytic asymmetric methods for producing enantioenriched organohalides, particularly axially chiral vinyl halides, remain underdeveloped. Here, we present a Cu(I)-catalyzed, highly enantioselective radical alkyne 1,2-halofunctionalization, utilizing custom-designed tridentate anionic N,N,N-ligands with bulky peripheral substituents. This method efficiently employs (hetero)aryl alkyl sulfonyl chlorides, as well α-carbonyl bromides, precursors utilizes diverse range of 2-amino 2-oxy aryl terminal alkynes substrates produce halides. The reaction is scalable gram quantities, the halides can be further transformed into thiourea, pyridyl carboxamide, quinolyl sulfonamide compounds, some which show significant potential catalysis. Both experimental theoretical mechanistic studies support an halogen atom transfer mechanism. opens avenue accessing facilitating broad applications various related fields.

Language: Английский

Enantioselective synthesis of molecules with multiple stereogenic elements DOI Creative Commons
Arthur Gaucherand, Expédite Yen‐Pon,

Antoine Domain

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(22), P. 11165 - 11206

Published: Jan. 1, 2024

This review explores the fascinating world of molecules featuring multiple stereogenic elements, unraveling different strategies designed over years for their enantioselective synthesis.

Language: Английский

Citations

12
Silanes as a versatile hydride source for Ni–H catalysis: a promising tool for π-hydro functionalization DOI
Yafia Kousin Mirza, Partha Sarathi Bera, Sachin Balaso Mohite

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(15), P. 4290 - 4317

Published: Jan. 1, 2024

Nickel-catalyzed hydrofunctionalization of π-substrates is a possibly effective method to synthesize several value-added molecular architectures. This review covers the NiH catalyzed reactions alkenes, alkynes and allenes.

Language: Английский

Citations

6
CF2H-synthon enables asymmetric radical difluoroalkylation for synthesis of chiral difluoromethylated amines DOI Creative Commons
Peng Liu, Yan He, Chenhui Jiang

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 11, 2025

The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by lower reactivity reduced enantioselectivity. Leveraging unique fluorine effect, we design synthesize radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild reaction conditions excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules. moiety, screening. authors

Language: Английский

Citations

0
Multimodal Precise Control Over Multiselective Carbonylation of 1,3-Enynes DOI Creative Commons
Chang‐Sheng Kuai, Yuanrui Wang, Ting Yang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7950 - 7964

Published: Feb. 19, 2025

Efficiently constructing structurally diverse and complex organic molecules through selective catalytic functionalization is a central goal in synthetic chemistry, yet achieving precise control over multiple reactive centers multisite substrates remains formidable challenge. Building on foundational advances single- dual-selective transformations, we report multimodal strategy for the carbonylation of 1,3-enynes, versatile class substrates. Through meticulous fine-tuning conditions, our approach enables five distinct regio- stereoselective carbonylative including direct (1,2- 2,1-hydroaminocarbonylation) tandem cyclization pathways (2,4-, 1,3-, 2,3-carbonylation). Furthermore, mechanistic studies suggested that multidimensional regulation seamless relay up to three reactions (hydroaminocarbonylation-hydroamination-transamination) with exceptional accuracy. This unified platform not only establishes robust framework tackling enduring challenges selectivity but also broadens chemical space accessible 1,3-enyne exemplifying atom- step-economic principles paving way transformative advancements drug discovery, materials science, beyond.

Language: Английский

Citations

0
Facile, general allylation of unactivated alkyl halides via electrochemically enabled radical-polar crossover DOI Creative Commons
Haifeng Chen, Magnus Rueping

Chemical Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We present a facile, general and transition-metal-catalyst free electrochemical allylation of unactivated alkyl halides. Broad substrate scopes, excellent functional group tolerance late-stage functionalization showcase its synthetic utility.

Language: Английский

Citations

0
Remote Enantioselective ε‐Alkylation of Copper Ethynylallenylidenes: Precise Control of Central and Axial Chirality DOI

Yu‐Hua Wen,

Minghao Liu, Yuhao Wang

et al.

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

Published: Oct. 17, 2024

Chiral tetrasubstituted allenes have emerged as important architectures for engineering biologically active compounds. The construction of unique allene scaffolds with precise control continuous central and axial chirality remains yet to be developed. Here, we report a remote enantioselective ϵ-alkylation yne-propargylic acetates enals enabled by NHC copper cooperative catalysis, leading series excellent enantioselectivities (up >99 % ee) diastereoselectivities >95 : 5 dr). This method features high regioselectivity simultaneous chirality. Mechanistic studies suggest activation mode synergistic distal created from the ethynylallenylidenes.

Language: Английский

Citations

2
The Difference in Ir-Catalyzed C(sp2)–H and C(sp3)–H Bond Activation Assisted by a Directing Group: Cyclometalation via Cis- or Trans-Chelation? DOI

Ling-Qi Meng,

Jian-Sen Wang,

Xiao-Xia You

et al.

Inorganic Chemistry, Journal Year: 2024, Volume and Issue: 63(38), P. 17626 - 17638

Published: Sept. 5, 2024

Iridium-catalyzed C-H borylation of aromatic and aliphatic hydrocarbons assisted by a directing group was theoretically investigated. Density functional theory (DFT) calculations revealed both Ir-catalyzed C(sp

Language: Английский

Citations

1
Enantio- and Regioselective Ni-Catalyzed Radical Relay 1,4-Arylalkylation of 1,3-Enynes to Access Chiral Tetrasubstituted Allenes DOI
Jinze Du,

Anyao Liu,

Wen Zhang

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(18), P. 13940 - 13946

Published: Sept. 5, 2024

Language: Английский

Citations

1
Remote Enantioselective ε‐Alkylation of Copper Ethynylallenylidenes: Precise Control of Central and Axial Chirality DOI

Yu‐Hua Wen,

Minghao Liu, Yuhao Wang

et al.

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

Published: Oct. 17, 2024

Abstract Chiral tetrasubstituted allenes have emerged as important architectures for engineering biologically active compounds. The construction of unique allene scaffolds with precise control continuous central and axial chirality remains yet to be developed. Here, we report a remote enantioselective ϵ‐alkylation yne‐propargylic acetates enals enabled by NHC copper cooperative catalysis, leading series excellent enantioselectivities (up >99 % ee) diastereoselectivities >95 : 5 dr). This method features high regioselectivity simultaneous chirality. Mechanistic studies suggest activation mode synergistic distal created from the ethynylallenylidenes.

Language: Английский

Citations

0
New CF2H-Synthon Enables Asymmetric Radical Difluoroalkylation for Synthesis of Chiral Difluoromethylated Amines DOI Creative Commons
Xi‐Sheng Wang, Peng Liu, Yan He

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 29, 2024

Abstract The difluoromethyl group (CF₂H) is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design screening. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by reaction scope, lower reactivity, reduced enantioselectivity. Leveraging unique fluorine effect, we designed synthesized novel radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild conditions, broad substrate excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules pharmaceutical research development.

Language: Английский

Citations

0