Nickel‐Catalyzed Tunable Enantioconvergence and Kinetic Resolution in the Coupling of Tertiary Cyclobutenols with Arylboroxines DOI
Xufei Yan,

Yulei Zhu,

Ying Xia

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(25)

Published: April 22, 2023

Abstract We report that a nickel catalyst system with modified 1,1′‐spirobiindane‐7,7′‐diol‐phosphoramidite (SPINOL) as the chiral ligand can enable coupling of tertiary cyclobutenols and arylboroxines in an enantioconvergent manner, providing cyclobutenes all‐carbon quaternary stereocenter good yields (up to 84 % yield) excellent enantioselectivities >99 ee). Moreover, catalytic be applied kinetic resolution under slightly conditions, giving enantioenriched s factor up >200. The reaction uses free hydroxyl groups leaving group without additional activation while strained ring remains untouched. Preliminary mechanistic studies reveal inherent discrepant reactivity two enantiomers is key controllable process.

Language: Английский

C(sp2)–H cyclobutylation of hydroxyarenes enabled by silver-π-acid catalysis: diastereocontrolled synthesis of 1,3-difunctionalized cyclobutanes DOI Creative Commons
Lei Tang, Qin-An Huang, Feng Wu

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(36), P. 9696 - 9703

Published: Jan. 1, 2023

Ring-opening of bicyclo[1.1.0]butanes (BCBs) is emerging as a powerful strategy for 1,3-difunctionalized cyclobutane synthesis. However, reported radical strain-release reactions are typically plagued with diastereoselectivity issues. Herein, an atom-economic protocol the highly chemo- and diastereoselective polar ring-opening BCBs hydroxyarenes catalyzed by π-acid catalyst AgBF4 has been developed. The use readily available starting materials, low loading, high selectivity (up to >98 : 2 d.r.), broad substrate scope, ease scale-up, versatile functionalizations products make this approach very attractive synthesis 1,1,3-trisubstituted cyclobutanes. Moreover, control experiments theoretical calculations were performed illustrate reaction mechanism selectivity.

Language: Английский

Citations

42
Enantioselective Synthesis of Chiral Cyclobutenes Enabled by Brønsted Acid-Catalyzed Isomerization of BCBs DOI

Si-Li Lin,

Ye‐Hui Chen, Huanhuan Liu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(39), P. 21152 - 21158

Published: Sept. 21, 2023

Chiral cyclobutene units are commonly found in natural products and biologically active molecules. Transition-metal-catalysis has been extensively used asymmetric synthesis of such structures, while organocatalytic approaches remain elusive. In this study, bicyclo[1.1.0]butanes involved enantioselective transformation for the first time to offer a highly efficient route toward cyclobutenes with good regio- enantiocontrol. The utilization N-triflyl phosphoramide as chiral Brønsted acid promoter enables isomerization process proceed under mild conditions low catalyst loading well functional group compatibility. resulting could serve platform molecules downstream manipulations excellent reservation stereochemical integrity, demonstrating synthetic practicality developed method. Control experiments have also performed verify formation key carbocation intermediate at benzylic position.

Language: Английский

Citations

40
Palladium-Catalyzed Divergent Enantioselective Functionalization of Cyclobutenes DOI

Zhonggui Wang,

Jie Zhu, Minyan Wang

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(18), P. 12691 - 12701

Published: April 27, 2024

Aliphatic strained rings have been increasingly applied in medicinal chemistry due to their beneficial physicochemical and pharmacokinetic properties. However, the divergent synthesis of enantioenriched cyclobutane derivatives with various structural patterns continues be a significant challenge. Here, we disclose palladium-catalyzed enantioselective desymmetrization cyclobutenes, resulting series hydroarylation 1,2- 1,3-diarylation products via interceptions common Heck intermediate. Mechanistic investigations provide valuable insights into understanding catalytic mode palladium catalysts observed variations deuterium-responsive behavior during reactions. Furthermore, synthetic utility is demonstrated syntheses deuterated drug candidate belaperidone skeletons pseudosymmetrical truxinic acid-type derivatives.

Language: Английский

Citations

9
Rhodium‐Catalyzed Asymmetric Arylation of Cyclobutenone Ketals DOI Creative Commons
David Egea‐Arrebola, F. Wieland Goetzke, Stephen P. Fletcher

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(13)

Published: Feb. 2, 2023

Complex cyclobutanes are important motifs in both bioactive molecules and natural products, yet their enantioselective preparation has not been widely explored. In this work, we describe rhodium-catalyzed additions of aryl vinyl boronic acids to cyclobutenone ketals. This transformation involves carbometalation give cyclobutyl-rhodium intermediates, followed by β-oxygen elimination afford enantioenriched enol ethers. Overall, addition serves as a surrogate for Rh-catalyzed 1,4-additions cyclobutenone.

Language: Английский

Citations

17
Nickel‐Catalyzed Tunable Enantioconvergence and Kinetic Resolution in the Coupling of Tertiary Cyclobutenols with Arylboroxines DOI
Xufei Yan,

Yulei Zhu,

Ying Xia

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(25)

Published: April 22, 2023

We report that a nickel catalyst system with modified 1,1'-spirobiindane-7,7'-diol-phosphoramidite (SPINOL) as the chiral ligand can enable coupling of tertiary cyclobutenols and arylboroxines in an enantioconvergent manner, providing cyclobutenes all-carbon quaternary stereocenter good yields (up to 84 % yield) excellent enantioselectivities >99 ee). Moreover, catalytic be applied kinetic resolution under slightly conditions, giving enantioenriched s factor up >200. The reaction uses free hydroxyl groups leaving group without additional activation while strained ring remains untouched. Preliminary mechanistic studies reveal inherent discrepant reactivity two enantiomers is key controllable process.

Language: Английский

Citations

12
Sc-Catalyzed Asymmetric [2 + 2] Annulation of 2-Alkynylnaphthols with Dienes to Access Cyclobutene Frameworks DOI
Ke Xu, Heping Li,

Yan‐Ling Ji

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 1006 - 1011

Published: Jan. 16, 2025

Herein, we introduce a scandium-catalyzed synthetic strategy that provides access to diverse and functionalized array of cyclobutene frameworks adorned with quaternary carbon center. This approach broadens the repertoire 2-alkynylnaphthols alkenes, offering versatile platform for construction complex molecular architectures. The asymmetric catalytic [2 + 2] cycloaddition reaction demonstrates wide substrate scope an impressive functional group tolerance, yielding products high efficiency, up 97% yield, excellent enantiomeric excess 97%. simplicity scaling this process, coupled ease converting these into variety substituted products, significantly enhances utility method.

Language: Английский

Citations

0
Visible-Light-Induced [2 + 2] Cyclization of Alkynes with Bromodifluoroacetylsilanes: Facile Access to gem-Difluorocyclobutenones DOI
Gang Zhou, Yongpeng Li, Ying Liu

et al.

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

Published: April 29, 2025

Herein, we report a simple and efficient method for the synthesis of gem-difluorocyclobutenones from alkynes bromodifluoroacetylsilanes, proceeding via formal cyclization with in situ generated difluoroketene under visible-light-induced conditions. The reaction conditions are mild exhibit broad substrate scope, including both aromatic aliphatic alkynes. Additionally, demonstrates good functional group tolerance, facile scalability, potential diverse downstream transformations. Mechanistic studies suggest that bromodifluoroacetylsilanes act as photochemical precursors to difluoroketene.

Language: Английский

Citations

0
Divergent Synthesis of 1,2,3,4‐Tetrasubstituted Cyclobutenes from a Common Scaffold: Enantioselective Desymmetrization by Dual‐Catalyzed Photoredox Cross‐Coupling DOI Creative Commons
Dawson J. Konowalchuk, Dennis G. Hall

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Oct. 19, 2023

Four-membered carbocycles are important structural motifs found in several natural products and drugs. Amongst those, cyclobutenes attractive intermediates because the residual olefin can be manipulated selectively into various saturated unsaturated analogs. Few methods exist to access chiral tri- tetra-C-substituted they generally limited terms of diversification. Herein, a divergent synthetic strategy was developed where single optically enriched scaffold is diversified variety derivatives with different substitution patterns. To this end, enantioselective desymmetrization prochiral 1,2-dibromocyclobutene imides enabled by dual Ir/Ni-catalyzed photoredox C(sp2 )-C(sp3 ) cross-coupling an alkyltrifluoroborate salt install convertible carbon fragment good yields >90 % enantiomeric excess. Exceptional mono-coupling selectivity observed resulting bromocyclobutene serves as common that transformed manner valuable 1,2,3,4-tetra-C-substituted cyclobutane while maintaining optical purity.

Language: Английский

Citations

8
Recent Advances in Asymmetric Synthesis of Chiral Cyclobutenes DOI Open Access
Fangdong Hu,

Yueting Zhao,

Lin Che

et al.

ChemCatChem, Journal Year: 2023, Volume and Issue: 16(3)

Published: Nov. 21, 2023

Abstract Cyclobutene scaffolds occur in natural products and bioactive compounds. Their unique structural features intrinsic ring strain make cyclobutene a type of important building block synthetic chemistry. In recent years, considerable efforts have been dedicated to the synthesis chiral cyclobutenes. Enantioselective [2+2] cycloadditions functionalization derivatives emerged as powerful reliable protocols for achieving this goal, resulting significant progress field. This review provides comprehensive summary advancements asymmetric cyclobutenes, discussion is logically divided into four parts according reaction mode.

Language: Английский

Citations

7
Rh(I)-Catalyzed Regio- and Enantioselective Ring Opening of Vinyl Cyclopropanes DOI Creative Commons
Stephen J. Webster,

László B. Balázs,

F. Wieland Goetzke

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(35), P. 24708 - 24715

Published: Aug. 20, 2024

We describe a Rh(I) catalyzed asymmetric ring opening of racemic vinyl cyclopropanes using aryl boronic acids as C-nucleophiles. When ferrocene-based chiral bisphosphines are used ligands, the products obtained with regioselectivities typically 99:1 r.r. and ee's generally between 88 96%. A wide range can be used, converted into variety targets. Preliminary mechanistic studies indicate that Zn(OTf)2 plays significant role in reaction by promoting rhodium-ligand complex formation accelerating reaction. expect this method these insights to useful development new methods.

Language: Английский

Citations

2