Atroposelective Three-Component (Fluoro)methylative Alkylation of Terminal Alkynes DOI

Yaheng Zhao,

Liping Huo,

Xiaoyu Zhao

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 15(1), P. 63 - 71

Published: Dec. 13, 2024

The development of synthetic methods for the selective installation methyl and fluoromethyl groups is highly desired due to their critical role in drug development. While significant advances have been made methylation difluoromethylation aromatic compounds, catalytic atroposelective (fluoro)methylative functionalization alkynes forge axially chiral alkenes remains underexploited. Herein, we report an enantioselective cross-electrophile strategy efficient 1,2-carbo-(fluoro)methylation with two different alkyl halides via nickel catalysis. By integrating a one-electron radical process two-electron organometallic process, this protocol employs simple catalyst effectively discriminate between secondary tertiary (fluoro)methyl alkyne difunctionalization. This demonstrates good compatibility activated secondary/tertiary bromides, terminal alkynes, halides, permitting straightforward synthesis broad range synthetically valuable (fluoro)methyl-substituted high chemo-, regio-, trans-, atropo-selectivity. Preliminary mechanistic studies provide insight into potential reaction pathway.

Language: Английский

Enantioselective 1,4-Borylamination via Copper-Catalyzed Cascade Hydroborylation and Hydroamination of Arylidenecyclopropanes DOI

Yu-Shen Zhu,

Yuecong Guo, Yingying Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(47), P. 32283 - 32291

Published: Nov. 13, 2024

Compounds bearing both boryl and amino groups at distal positions are invaluable synthons for synthesizing pharmaceuticals, drug candidates, natural products, but their catalytic enantioselective synthesis remains rarely explored. We report the first 1,4-borylamination reaction through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This combines four readily available components in highly chemo-, site-, fashion (>20:1 r.r. up to 99% ee), yielding diverse array synthetically valuable enantioenriched 4-amino alkylboronates. The versatile utility these products is highlighted by transformations wide applications pharmaceutical discovery. Preliminary mechanistic studies were conducted elucidate operative pathway, intermediates, origins its high chemo- site-selectivity.

Language: Английский

Citations

6
Enantioselective Copper-Catalyzed Three-Component Cascade Boronation–Dearomatization Reaction: Synthesis of Chiral Boron-Containing 1,4-Dihydropyridines DOI

Fazhou Yang,

Yujie Dong, Jinbao Wang

et al.

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

Published: Jan. 10, 2025

A three-component cascade boronation–dearomatization reaction of alkenes, a diboron compound, and pyridinium salt is diclosed, affording chiral boron-containing 1,4-dihyropyridines in high yields (≤98%) diastereoselectivity (≤10:1 dr), along with excellent enantioselectivity (typically >99% ee). The catalytic system performs efficiently at low catalyst loadings (1 mol %) was tested >50 examples, including some biologically active molecules.

Language: Английский

Citations

0
Palladium-Catalyzed Intermolecular 1,3-Dienylation of Propargyl Esters Involving the Insertion of SO2 DOI

Haohao Jiang,

Mengzhao Yu,

Shuoshuo Zhang

et al.

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

Published: Feb. 20, 2025

A palladium-catalyzed three-component 1,3-dienylation of propargylic esters with DABSO and aryl iodides has been developed. This novel reductive cross-coupling reaction produces 2-sufonylated 1,3-dienes as single products in the presence metal Mn high regio- chemoselectivities. Control experiments demonstrated that transformation may undergo a radical process.

Language: Английский

Citations

0
Approach Toward Stereoselective α‐Arylation by Pd/Cu‐Catalyzed Arylboration of Electron Deficient Alkenes DOI Creative Commons
Suman Das,

Michael Reilly,

Stanna K. Dorn

et al.

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Palladium‐catalyzed cross coupling of enolates—α‐arylation—is an established method for chemical synthesis. A major challenge in the field is control stereochemistry α‐carbon. This typically due to facile epimerization under basic reaction conditions α‐arylation. In this study, alternative approach presented that involves Pd/Cu‐catalyzed arylboration electron deficient alkenes. The products are generated with high levels diastereoselectivity a broad range substitution patterns. Enantioselective variants also addition product derivatizations.

Language: Английский

Citations

0
Approach Toward Stereoselective α‐Arylation by Pd/Cu‐Catalyzed Arylboration of Electron Deficient Alkenes DOI Creative Commons
Suman Das,

Michael Reilly,

Stanna K. Dorn

et al.

Angewandte Chemie, Journal Year: 2025, Volume and Issue: unknown

Published: March 27, 2025

Abstract Palladium‐catalyzed cross coupling of enolates—α‐arylation—is an established method for chemical synthesis. A major challenge in the field is control stereochemistry α‐carbon. This typically due to facile epimerization under basic reaction conditions α‐arylation. In this study, alternative approach presented that involves Pd/Cu‐catalyzed arylboration electron deficient alkenes. The products are generated with high levels diastereoselectivity a broad range substitution patterns. Enantioselective variants also addition product derivatizations.

Language: Английский

Citations

0
Enantioselective 1,4-Borylamination Enabled by Copper Catalysis DOI
Bo Su, Yu‐Jie Zhu

Synlett, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Compounds bearing both boryl and amino groups are highly valuable synthons in organic synthesis. However, while enantioselective 1,1- 1,2-borylamination reactions have been developed, processes enabling distal borylamination rarely investigated. Here, we present an 1,4-borylamination reaction, achieved through a copper-catalyzed cascade hydroborylation hydroamination of arylidenecyclopropanes. This four-component reaction provides direct access to enantioenriched 4-aminoalkylboronate products with high chemo-, site-, enantioselectivity. The versatility these was demonstrated their broad transformations extensive applications the synthesis various drug core structures. Additionally, preliminary mechanistic studies were conducted investigate pathway, intermediates, chemo- site-selectivity.

Language: Английский

Citations

0
Cu-catalyzed enantioselective assembly of axially chiral allylic boronates DOI
Shuai Wang, Jianbo Liu,

Wenyue Ma

et al.

Science China Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Language: Английский

Citations

2
Atroposelective Three-Component (Fluoro)methylative Alkylation of Terminal Alkynes DOI

Yaheng Zhao,

Liping Huo,

Xiaoyu Zhao

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 15(1), P. 63 - 71

Published: Dec. 13, 2024

The development of synthetic methods for the selective installation methyl and fluoromethyl groups is highly desired due to their critical role in drug development. While significant advances have been made methylation difluoromethylation aromatic compounds, catalytic atroposelective (fluoro)methylative functionalization alkynes forge axially chiral alkenes remains underexploited. Herein, we report an enantioselective cross-electrophile strategy efficient 1,2-carbo-(fluoro)methylation with two different alkyl halides via nickel catalysis. By integrating a one-electron radical process two-electron organometallic process, this protocol employs simple catalyst effectively discriminate between secondary tertiary (fluoro)methyl alkyne difunctionalization. This demonstrates good compatibility activated secondary/tertiary bromides, terminal alkynes, halides, permitting straightforward synthesis broad range synthetically valuable (fluoro)methyl-substituted high chemo-, regio-, trans-, atropo-selectivity. Preliminary mechanistic studies provide insight into potential reaction pathway.

Language: Английский

Citations

0