Enantioselective Synthesis of Chiral γ‐Amino Acid Esters via Photoredox/Nickel‐Catalyzed Aryl‐Aminoalkylation of Alkenes DOI
Ye Fu, Youzhi Xu,

Songlin Zheng

et al.

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

Comprehensive Summary Chiral γ ‐amino acids are among the most valuable and ubiquitous structural units in natural products, pharmaceuticals many physiologically active compounds. Herein, we demonstrate a convenient synthetic approach to chiral acid structures via an asymmetric aryl‐aminoalkylation of alkenes enabled by dual photoredox/nickel catalysis. Taking advantage mild redox‐neutral condition, high levels enantiocontrol α ‐carbonyl benzylic stereocenters obtained. Experimental computational mechanistic studies were performed gain insights into mechanism origin enantioselectivity. The results reveal that reaction follows Ni(0)/Ni(I)/Ni(III)/Ni(I) catalytic cycle C–X bond oxidative addition is enantiodetermining step.

Language: Английский

Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis DOI Creative Commons
Lauren E. Ehehalt, Omar M. Beleh, Isabella C. Priest

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Cross-electrophile coupling (XEC), defined by us as the cross-coupling of two different σ-electrophiles that is driven catalyst reduction, has seen rapid progression in recent years. As such, this review aims to summarize field from its beginnings up until mid-2023 and provide comprehensive coverage on synthetic methods current state mechanistic understanding. Chapters are split type bond formed, which include C(sp

Language: Английский

Citations

24
O-Allylhydroxyamine: A Bifunctional Olefin for Construction of Axially and Centrally Chiral Amino Alcohols via Asymmetric Carboamidation DOI

Ruijie Mi,

Zhiying Ding,

Songjie Yu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(14), P. 8150 - 8162

Published: April 4, 2023

Difunctionalization of olefins offers an attractive approach to access complex chiral structures. Reported herein is the design N-protected O-allylhydroxyamines as bifunctional that undergo catalytic asymmetric 1,2-carboamidation with three classes (hetero)arenes afford amino alcohols via C-H activation. The C═C bond in O-allylhydroxyamine activated by intramolecular electrophilic amidating moiety well a migrating directing group. carboamidation reaction pattern depends on nature (hetero)arene reagent. Simple achiral reacted give centrally β-amino excellent enantioselectivity. employment axially prochiral or racemic heteroarenes afforded both axial and central chirality enantio- diastereoselectivity. In case heteroarenes, coupling follows kinetic resolution s-factor up >600. A nitrene-based mechanism has been suggested based experimental studies, unique mode induction diastereoselectivity proposed. Applications alcohol products have demonstrated.

Language: Английский

Citations

38
Enantioselective Directed Nickel-Catalyzed Three-Component Reductive Arylalkylation of Alkenes via the Carbometalation/Radical Cross-Coupling Sequence DOI

Zhan Dong,

Changyu Xu,

Jianchao Chang

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 4395 - 4406

Published: March 8, 2024

Asymmetric reductive three-component arylalkylation of alkenes via the radical relay method has been well established, while asymmetric migratory insertion strategy remains unexplored. We report enantioselective nickel-catalyzed cross-electrophile with aryl- and alkyl halides an integrated Heck carbometalation/radical cross-coupling sequence. This protocol employing a chiral Ni/PHOX catalytic system allows terminal internal to successfully engage exquisite control regio-, chemo-, stereoselectivity. More importantly, this undergoes regio- arylnickelation followed by Csp3–Csp3 elimination, thus exhibiting reverse regioselectivity method. Mild reaction conditions exceptional functional group tolerance facilitate method's compatibility bioactive motifs modular synthesis biologically active compounds. The experiments density theory calculations provide insights into mechanism origin stereoselectivity, hemilabile nature PHOX ligand is critical for achieving arylalkylation.

Language: Английский

Citations

15
Transition‐Metal‐Mediated Fluoroalkylation of Carbon Electrophiles through Cross‐Electrophile Couplings DOI
Yun‐Cheng Luo, Xingang Zhang

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Comprehensive Summary Organofluorine compounds have attracted substantial interest in life and materials sciences due to the unique properties of fluorine atom(s) that often change physicochemical biological organic molecules. Transition‐metal‐mediated cross‐electrophile coupling between carbon electrophiles fluoroalkyl has emerged as a straightforward efficient route for synthesis wide range fluoroalkylated because its synthetic convenience without tedious organometallic reagents. Moreover, alkenes or alkynes‐involved three‐component couplings provide rapid effective access carbonfunctionalized alkanes alkenes. Herein, we comprehensively summarize transition‐metal‐mediated reductive fluoroalkylation diverse through historical perspective, including trifluoromethylation, difluoroalkylation, monofluoroalkylation, so on. Different transition metals (Cu, Ni, etc .) strategies are discussed, which nickel‐catalyzed reactions represent an attractive site‐selectively organofluorine compounds. Key Scientists As early 1965, McLoughlin Thrower finished first stoichiometric copper‐mediated aromatic iodides with iodides. However, excess elevated temperature were used this method. In 1969, Kobayashi Kumadaki reported studies on trifluoromethylation halides trifluoromethyl iodide. After more than four decades, Zhang group developed β ‐fluorinated alkylation (hetero)aryl secondary alkyl bromides 2015, difluoromethylation chlorides chlorodifluoromethane ClCF 2 H 2017. The also enantioselective alkyl‐arylation 3,3,3‐trifluoropropene tertiary 2018, MacMillan novel copper/photoredox dual catalytic system aryl ( S )‐(trifluoromethyl) dimesitylsulfonium triflate presence tris‐(trimethylsilyl) silanol. They nickel/photoredox catalyzed silane. During time, Wang monofluoroalkylation monofluoroalkyl halides. From 2021 2023, same further series trifluoroalkylation aryl, alkenyl, acyl nonfluorinated alkynes could be couplings. Chu fluoroalkyl‐acylation Later, they fluoroalkyl‐arylation unactivated tethering pendant chelating group. 2019, Chaładaj palladium‐catalyzed perfluoroalkyl‐arylation perfluoroalkyl

Language: Английский

Citations

12
Ni- and Pd-Catalyzed Enantioselective 1,2-Dicarbofunctionalization of Alkenes DOI
Taeho Kang,

Omar Apolinar,

Keary M. Engle

et al.

Synthesis, Journal Year: 2023, Volume and Issue: 56(01), P. 1 - 15

Published: June 12, 2023

Abstract Catalytic enantioselective 1,2-dicarbofunctionalization (1,2-DCF) of alkenes is a powerful transformation growing importance in organic synthesis for constructing chiral building blocks, bioactive molecules, and agrochemicals. Both two- three-component context, this family reactions generates densely functionalized, structurally complex products single step. Across several distinct mechanistic pathways at play these transformations with nickel or palladium catalysts, stereocontrol can be obtained through tailored ligands. In Review we discuss the various strategies, mechanisms, catalysts that have been applied to achieve enantioinduction alkene 1,2-DCF. 1 Introduction 2 Two-Component Enantioselective 1,2-DCF via Migratory Insertion 3 Radical Capture 4 Three-Component 5 6 Miscellaneous Mechanisms 7 Conclusion

Language: Английский

Citations

24
Nickel-Catalyzed Asymmetric Cross-Electrophile trans-Aryl-Benzylation of α-Naphthyl Propargylic Alcohols DOI
Zhiyang Lin,

Weitao Hu,

Linchuan Zhang

et al.

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(10), P. 6795 - 6803

Published: May 3, 2023

Herein, we report a nickel-catalyzed asymmetric three-component trans-dicarbofunctionalization of β-substituted α-naphthyl propargylic alcohols using readily available aryl and benzyl halides as the coupling partners under reductive conditions. This cross-electrophile strategy enables synthesis various axially chiral allylic bearing tetrasubstituted olefinic unit in complete regio- E selectivity, well high enantiocontrol. Relying on hydroxyl group functional handle, such structural motifs are successfully derivatized into diverse functional-group-rich alkenes.

Language: Английский

Citations

19
Enantioselective Ni‐Catalyzed Three‐Component Dicarbofunctionalization of Alkenes DOI Open Access

Zhan Dong,

Liangliang Song, Liang‐An Chen

et al.

ChemCatChem, Journal Year: 2023, Volume and Issue: 15(18)

Published: Aug. 3, 2023

Abstract Asymmetric multicomponent reactions are considered as efficient protocols for constructing complex chiral molecules because of their step‐ and atom‐economy. Nickel‐catalyzed asymmetric three‐component dicarbofunctionalization alkenes has been well developed in recent years, which is used the area total synthesis natural products late‐stage modification drugs rapid incorporation sp 3 ‐enriched carbon centers. In this concept, significant breakthroughs field summarized, together with related mechanisms. Moreover, remaining challenges potential opportunities also highlighted.

Language: Английский

Citations

19
Ball-milling-enabled nickel-catalyzed radical relayed reductive cross-coupling DOI Creative Commons
Chunying Fan, Bobo Wang, Tianle Wu

et al.

Cell Reports Physical Science, Journal Year: 2024, Volume and Issue: 5(2), P. 101831 - 101831

Published: Feb. 1, 2024

Nickel-catalyzed radical relayed dicarbofunctionalizations of olefins, utilizing carbon electrophiles as coupling partners, present a powerful strategy for the streamlined construction aliphatic structures. However, traditional solution-phase methods encounter challenges such need bulk solvents, limited long reaction times, and air-/moisture-sensitive reagents. As an alternative strategy, ball-mill-enabled metal-catalyzed cross-coupling reactions have gained attention due to their high reactivity atomic efficiency. While many are single- two-component methodologies, three-component solid-state remain relatively scarce. In this work, we report first, our knowledge, ball-milling-enabled Ni-catalyzed reductive dicarbofunctionalization alkenes. Two distinct readily available electrophiles, Csp2 Csp3 halides, simultaneously installed across variety olefins at room temperature in highly regioselective manner withing 1.5 h. By harnessing benefits ball milling reactions, anticipate further advancements sustainable efficient synthetic methodologies.

Language: Английский

Citations

8
Metallaphotoredox-Catalyzed Three-Component Asymmetric Cross-Electrophile Coupling for Chiral Boronate Synthesis DOI
Xiaofang Li, Yuntong Hu,

Zhonghou Huang

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(20), P. 15790 - 15798

Published: Oct. 10, 2024

Here, we report a photoredox and nickel-catalyzed cross-electrophile coupling strategy for the asymmetric three-component 1,2-alkylarylation of vinyl boronates with (hetero)aryl bromides (2°, 3°)-alkyl redox-active esters in presence Hantzsch ester. With fluorinated pyridyl-substituted chiral biimidazoline ligand, this reaction enables straightforward access to wide variety synthetically valuable α-aryl from readily available starting materials. This features mild conditions, broad substrate generality, good functional group tolerance proceeds without using metal reductants or alkyl halides. Furthermore, alkenyl halides other electron-deficient alkenes such as acrylates phosphonates can be applied successfully. Preliminary mechanistic studies shed light on potential pathways roles organic amines.

Language: Английский

Citations

7
Modular Access to Chiral Benzylamines via Ni/Photoredox-Catalyzed Multicomponent Cross-Electrophile Coupling DOI

Panting Cao,

Wenhui Xiong,

Tao Yang

et al.

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

Published: Jan. 30, 2025

A Ni/photoredox dual-catalyzed multicomponent cross-electrophile coupling of N-vinyl amides with (hetero)aryl halides and (2°, 3°)-alkyl redox-active esters in the presence cheap reductant Hantzsch ester is reported here. This reductive protocol provides direct access to various synthetically challenging chiral α-arylamides good yields excellent enantioselectivities (up 99% ee, majority exceeding 97% ee), which can be further derived into primary secondary amines. Preliminary experimental studies shed light on potential catalytic pathways.

Language: Английский

Citations

1