Asymmetric synthesis of β-amino acid derivatives by stereocontrolled C(sp3)-C(sp2) cross-electrophile coupling via radical 1,2-nitrogen migration DOI Creative Commons
Shi Tang,

Zi-Cheng Liao,

Mengwu Xiao

et al.

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

Published: Nov. 26, 2024

Abstract Optically pure non-natural β-amino acids are noteworthy molecular motifs of numerous pharmaceutically important molecules. Skeletal editing abundant α-amino acid scaffolds via tandem radical 1,2-N-shift/cross-coupling represents an attractive and powerful tool to straightforward assemble new molecules; however, this strategy presents substantial challenges owing difficulties in reactivity regio-/enantiocontrol. Herein, we report unprecedented remote cross-electrophile C(sp2)-C(sp3) coupling β-bromo esters with aryl bromides a π-system-independent 1,2-N-shift, which allows access α-arylated β-amino high efficiency regioselectivity. Furthermore, upon the novel cooperative catalysis Ni(II)/new-style Box complex chiral phosphoric (CPA), migratory further achieves enantioselectivity control C(sp3)–C(sp2) bond construction. In addition, detailed experimental studies DFT calculations were conducted gain insight into mechanism origin enantioselectivity, was evidenced by two-step synthesis pan-Akt inhibitor molecule. Overall, synergistic expands these methods challenging enantioselective C(sp2)–C(sp3) 1,2-amino migration.

Language: Английский

Asymmetric construction of enantioenriched furo[2,3-b]pyridines through sequential gold, palladium/phosphoric acid catalysis DOI
Ke Xie, Guoqing Zhang,

Bao-Rui Kong

et al.

Organic Chemistry Frontiers, Journal Year: 2024, Volume and Issue: 11(14), P. 3900 - 3905

Published: Jan. 1, 2024

A multi-catalytic system combining gold, palladium and phosphoric acid was applied for asymmetric assembly of ynamides carbonate 4-hydroxy-2-cyclopentenone, furnishing furo[2,3- b ]pyridines in high yields stereoselectivities.

Language: Английский

Citations

3
Catalyst-controlled regiodivergence and stereodivergence in formal cross-[4+2] cycloadditions: The unique effect of bismuth(III) DOI
Qiumeng Hou,

Chenxi Cai,

Shuai‐Jiang Liu

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(13)

Published: March 26, 2025

The [4+2] cycloaddition is crucial for constructing six-membered rings in pharmaceuticals and natural products. Cross-[4+2] cycloadditions offer greater product diversity than traditional diene-dienophile reactions due to multiple possible pathways. However, precise control over regio- stereoselectivity various isomers remains a great challenge. This study reports catalyst-controlled regiodivergent formal cross-cycloadditions of acyclic dienes enones, significantly enhancing access diverse pyrazole-fused spirooxindoles. Chiral phosphoric acid (CPA) catalysis enables endoselective cycloadditions, while Bi(III) with CPA ligand yields [2+4] products high stereoselectivity. A Claisen rearrangement the adduct produces exo-selective product, further increasing stereochemical enabling synthesis six stereo-isomers from single substrate set. DFT calculations reveal that reverses regioselectivity by repositioning reactants pocket stabilizing enone oxygen’s negative charge. In addition, 3as demonstrates therapeutic potential against triple-negative breast cancer, an IC 50 8.5 μM MDA-MB-453 cells.

Language: Английский

Citations

0
Asymmetric Synthesis of 1,3-Cyclohexadienes Enabled by Pd/Chiral Phosphoric Acid Cooperative Catalysis DOI
Mark Lautens, Colton E. Johnson

Synfacts, Journal Year: 2024, Volume and Issue: 20(05), P. 0493 - 0493

Published: April 15, 2024

Key words palladium catalysis - cooperative asymmetric cycloaddition

Language: Английский

Citations

0
Facile construction of 2-pyrones under carbene catalysis DOI Creative Commons
Miao Yu, Jie Huang, Haibin Zhu

et al.

RSC Advances, Journal Year: 2024, Volume and Issue: 14(39), P. 28585 - 28595

Published: Jan. 1, 2024

2-Pyrones are valuable structural motifs in organic chemistry, found numerous natural products and pharmaceuticals. The synthesis of these heterocycles has been significantly advanced by the application N-Heterocyclic Carbene (NHC) catalysis. This review examines recent advancements NHC-catalyzed 2-pyrones, highlighting key methodologies, mechanisms, synthetic applications. NHC catalysis revolutionized providing efficient, selective, versatile methods for constructing heterocycles.

Language: Английский

Citations

0
Catalytic asymmetric inverse-electron-demand Diels–Alder reaction of 2-pyrones with aryl enol ethers DOI
Fangqing Zhang, Yu Wang, Zhenda Tan

et al.

Chinese Chemical Letters, Journal Year: 2024, Volume and Issue: unknown, P. 110581 - 110581

Published: Oct. 1, 2024

Language: Английский

Citations

0
Asymmetric synthesis of β-amino acid derivatives by stereocontrolled C(sp3)-C(sp2) cross-electrophile coupling via radical 1,2-nitrogen migration DOI Creative Commons
Shi Tang,

Zi-Cheng Liao,

Mengwu Xiao

et al.

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

Published: Nov. 26, 2024

Abstract Optically pure non-natural β-amino acids are noteworthy molecular motifs of numerous pharmaceutically important molecules. Skeletal editing abundant α-amino acid scaffolds via tandem radical 1,2-N-shift/cross-coupling represents an attractive and powerful tool to straightforward assemble new molecules; however, this strategy presents substantial challenges owing difficulties in reactivity regio-/enantiocontrol. Herein, we report unprecedented remote cross-electrophile C(sp2)-C(sp3) coupling β-bromo esters with aryl bromides a π-system-independent 1,2-N-shift, which allows access α-arylated β-amino high efficiency regioselectivity. Furthermore, upon the novel cooperative catalysis Ni(II)/new-style Box complex chiral phosphoric (CPA), migratory further achieves enantioselectivity control C(sp3)–C(sp2) bond construction. In addition, detailed experimental studies DFT calculations were conducted gain insight into mechanism origin enantioselectivity, was evidenced by two-step synthesis pan-Akt inhibitor molecule. Overall, synergistic expands these methods challenging enantioselective C(sp2)–C(sp3) 1,2-amino migration.

Language: Английский

Citations

0