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

Atroposelective catalysis DOI

Tanno A. Schmidt,

Valeriia Hutskalova,

Christof Sparr

et al.

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(7), P. 497 - 517

Published: June 18, 2024

Language: Английский

Citations

16
Mechanism and Origin of Stereoselectivity for the NHC-Catalyzed Desymmetrization Reaction for the Synthesis of Axially Chiral Biaryl Aldehydes DOI
Xiaoxiao Hou, Donghui Wei

The Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 89(5), P. 3133 - 3142

Published: Feb. 15, 2024

Organocatalytic desymmetrization reaction is a powerful tool for constructing axial chirality, but the theoretical study on origin of stereoselectivity still lags behind even now. In this work, N-heterocyclic carbene (NHC)-catalyzed biaryl frameworks synthesis axially chiral aldehydes has been selected and theoretically investigated by using density functional theory (DFT). The fundamental pathway involves several steps, i.e., desymmetrization, formation Breslow oxidation, esterification, NHC regeneration. processes have identified as stereoselectivity-determining rate-determining steps. Further weak interaction analyses proved that C–H···O hydrogen bond C–H···π interactions are responsible stability key stereoselective transition states. This research contributes to understanding nature NHC-catalyzed reactions compounds.

Language: Английский

Citations

14
Organocatalytic Atroposelective Dynamic Kinetic Resolution Involving Ring Manipulations DOI

Qin Shi,

Fang Fang, Dao‐Juan Cheng

et al.

Advanced Synthesis & Catalysis, Journal Year: 2024, Volume and Issue: 366(6), P. 1269 - 1284

Published: Jan. 31, 2024

Abstract Axially chiral architectures exist widely in natural products, biologically relevant molecules, ligands and catalysts as well functional materials. Therefore, catalytic asymmetric synthesis of atropisomers has become one the most fast‐growing fields community chemistry rapid advances have occurred. Among different methods reported, organocatalytic atroposelective dynamic kinetic resolution (DKR) involving ring manipulations stands out a cutting‐edge technology to construct axial chirality from point atom/step economy. In this DKR strategy, configurational lability starting materials originates chirally‐labile structure cyclic substrates/intermediates or transient formation through noncovalent interactions acyclic substrates. The two material are equilibrium reaction medium, ensuring constant transformation less reactive atropisomer into more one, then single enantiopure product presence an appropriate organocatalyst. This review summarizes recent advancements on topic, including their scopes, limitations, mechanisms, applications provides some insights further developments.

Language: Английский

Citations

11
Copper- and Palladium-Cocatalyzed Chemo-, Regio-, Stereo-, and Atroposelective Arylboration of 1,3-Enynes DOI
Wangyang Li, Haohua Chen,

Yanping Zheng

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(15), P. 11318 - 11331

Published: July 15, 2024

Catalytic enantioselective borylation reactions of unsaturated bonds as powerful tools for the synthesis diverse chiral organoboron compounds have gained much attention and wide applications in various fields. However, atroposelective arylboration reaction with carbon–carbon triple 1,3-enynes to obtain axially 1,3-dienylboronates remains an elusive significant challenge. Hence, we develop a cooperative copper- palladium-catalyzed assemble plentiful function enriched single step from easily available 1,3-enynes, B2pin2, aryl bromides high levels chemo-, regio-, stereo-, atroposelectivity. The mild conditions lead good functional group tolerance, which is proven by broad substrate scope late-stage functionalizations bioactive or drug molecules. Moreover, can be scaled up, series further transformations achieved. It worth emphasizing that several olefin catalysts ligands axial chirality also synthesized through corresponding elaborations such products, explains transformative ability application potential 1,3-dienylboronates. mechanism experiment density theory (DFT) calculations revealed process copper palladium catalysis, indicating chemoselectivity regioselectivity boration are determined enyne insertion on copper, atroposelectivity controlled reductive elimination center. Meanwhile, calculation demonstrated distinct interactions between P═O C═O groups Pd Bpin center key transition state formation products varying configurations while employing identical configuration ligands.

Language: Английский

Citations

8
Recent advances in organocatalytic atroposelective reactions DOI Creative Commons

Henrich Szabados,

Radovan Šebesta

Beilstein Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 21, P. 55 - 121

Published: Jan. 9, 2025

Axial chirality is present in a variety of naturally occurring compounds, and becoming increasingly relevant also medicine. Many axially chiral compounds are important as catalysts asymmetric catalysis or have chiroptical properties. This review overviews recent progress the synthesis via organocatalysis. Atroposelective organocatalytic reactions discussed according to dominant catalyst activation mode. For covalent organocatalysis, typical enamine iminium modes presented, followed by N -heterocyclic carbene-catalyzed reactions. The bulk devoted non-covalent activation, where Brønsted acids feature most prolific catalytic structure. last part article discusses hydrogen-bond-donating other motifs such phase-transfer catalysts.

Language: Английский

Citations

1
Organocatalytic Atroposelective Hydroselenation of Alkynes To Access Axially Chiral Vinyl Selenides DOI

Yi-Xin Wang,

Jing-Run Wang,

Chen Cui

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4051 - 4060

Published: Feb. 20, 2025

Language: Английский

Citations

1
Copper-catalysed dynamic kinetic asymmetric C−O cross-coupling to access chiral aryl oxime ethers and diaryl ethers DOI Creative Commons

Meiru Zhang,

Haoran Wang,

Hui-Mei Shan

et al.

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

Published: March 13, 2025

Dynamic kinetic resolution (DKR) has emerged as an elegant and powerful tool for enantioselective synthesis, enabling the transformation of racemic compounds into enantiomerically enriched products with theoretically quantitative yields. Despite its widespread success, dynamic asymmetric C−O cross-coupling presented significant challenges remains unexplored. In this study, we report a oximes phenols via copper/BOX-catalysed O-arylation diaryliodonium salts. This method efficiently produces wide range inherently chiral oxime ethers, well axially styrenes, high yields excellent regio- enantioselectivities. Through controlled experiments Density Functional Theory (DFT) studies, have elucidated process gained insights origins enantioselectivity. The Here, authors

Language: Английский

Citations

1
Novel Stereo‐Induction Pattern in Pudovik Addition/Phospha‐Brook Rearrangement Towards Chiral Trisubstituted Allenes DOI

Jia‐Yan Zheng,

Handong Wang, Yan Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 23, 2024

Abstract Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity reports on axially allenyl phosphorus compounds. Here, we disclosed an efficient straightforward cascade reaction between ethynyl ketones phosphine oxides, resulting broad array trisubstituted allenes incorporating moiety high yields with excellent stereoselectivities facilitated by peptide‐mimic phosphonium salt (PPS) Additionally, comprehensive series mechanistic experiments have been conducted to elucidate that this proceeds via asymmetric Pudovik addition followed subsequent phospha ‐Brook rearrangement occurs concomitantly kinetic resolution, representing stereospecific protonation process facilitating central‐to‐axial chirality transfer manner. We anticipate our research will pave way for promising exploration novel stereo‐induction pattern addition/ reaction.

Language: Английский

Citations

8
Development of Configurationally Labile Biaryl Reagents for Atropisomer Synthesis DOI
Changhui Wu, Jin Yang,

Xiaoyuan Zhang

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 27(28)

Published: May 16, 2024

Abstract Axially chiral biaryl scaffolds are important in pharmaceuticals, natural products, and asymmetric synthesis. Atroposelective ring‐opening of configurationally labile reagents via dynamic kinetic transformation provides a valuable approach to access axially atropisomers. This review summarizes seminal contributions recent advancements on this topic based the use different types reagents.

Language: Английский

Citations

6
Engineered enzymes for enantioselective nucleophilic aromatic substitutions DOI Creative Commons

Thomas M. Lister,

George W. Roberts, Euan J. Hossack

et al.

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

Published: Jan. 15, 2025

Language: Английский

Citations

0