Nickel-Catalyzed Enantioselective Arylative Cyclization of Alkyne-Oxime Ethers: Access to Chiral Hydroxylamine Ethers

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

Published: March 27, 2025

Chiral hydroxylamines serve as essential scaffolds in modern organic synthesis and are of significant interest drug discovery. Although asymmetric hydrogenation oximes is well-established, the development metal-catalyzed oxime ethers addition reactions, especially those employing earth-abundant metal catalysts, has remained limited. Herein, we report first nickel-catalyzed ethers, providing chiral hydroxylamine moderate to excellent yields (up 94%) with generally enantioselectivities 99% ee). Moreover, this method enables construction bearing multiple contiguous stereocenters via a substrate-controlled diastereoselective process.

Language: Английский

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Recent developments in enantioselective nickel-catalysed cycloadditions

Tetrahedron, Journal Year: 2024, Volume and Issue: 153, P. 133840 - 133840

Published: Jan. 20, 2024

Language: Английский

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Ni‐Catalyzed Enantioselective Difunctionalization of Alkynes to Azepine Derivatives Bearing a Quaternary Center and an Unprotected Imine^†

Chinese Journal of Chemistry, Journal Year: 2023, Volume and Issue: 42(8), P. 873 - 878

Published: Dec. 26, 2023

Comprehensive Summary The azepine ring is a prominent structural scaffold in biologically significant molecules. In this study, we present Ni(II)‐catalyzed asymmetric difunctionalization of alkynes, involving intermolecular regioselective arylation and intramolecular nitrile addition, enabling the synthesis enantioenriched derivatives. This reaction simultaneously installs an all‐carbon quaternary stereocenter introduces unprotected imine functionality, showing great promise for subsequent transformations. exhibits good tolerance toward various functional groups, resulting high yields enantioselectivities. synthetic utility methodology further demonstrated through gram‐scale product derivatization. research offers efficient approach to seven‐membered nitrogen heterocycles.

Language: Английский

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Access to Alkenyl Cyclobutanols by Ni‐Catalyzed Regio‐ and Enantio‐selective syn‐Hydrometalative 4‐exo‐trig Cyclization of Alkynones

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

Abstract Enantioselective synthesis of (spiro)cyclobutane derivatives poses significant challenges yet holds promising applications for both synthetic and medicinal chemistry. We report here a nickel‐catalyzed asymmetric syn ‐hydrometalative 4‐ exo ‐ trig cyclization 1,4‐alkynones to synthesize alkenyl cyclobutanols with tetrasubstituted stereocenter. This strategy features broad substrate scope, delivering variety trifluoromethyl‐containing rigid (spiro)carbocycle skeletons in good yields high enantioselectivities (up 84 % yield 98.5 : 1.5 er). The utility is demonstrated through stereospecific transformations into fused spiro molecules. Experimental computational mechanistic studies indicate that the reaction initiated by an active Ni−H species, carbonyl‐directed hydrometalation as key regioselective control. catalytic method provides general solution hydrofunctionalization alkynes represents efficient pattern assembling highly strained enantioenriched bioisosteres.

Language: Английский

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Enantioselective Synthesis of 3‐Hydroxy‐2‐Oxindoles via Ni‐Catalyzed Asymmetric Addition of Aromatic Bromides to α‐Ketoamides

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract Nickel‐catalyzed asymmetric intramolecular addition of aryl halides to α‐ketoamides has been achieved afford chiral 3‐substituted‐3‐hydroxy‐2‐oxindoles in excellent yields and high enantioselectivities (up 99 % yield 98 ee), which provides efficient access valuable molecules containing 3‐hydroxy‐2‐oxindole core. The gram‐scale reaction proved the potential utility methodology.

Language: Английский

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Enantioselective Synthesis of 3-Hydroxy-2-Oxindoles via Ni-Catalyzed Asymmetric Addition of Aromatic Bromides to a-Ketoamides

Authorea (Authorea), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 30, 2024

Nickel-catalyzed asymmetric intramolecular addition of aryl halides to a-ketoamides has been achieved afford chiral 3-substituted-3-hydroxy-2-oxindoles in excellent yields and high enantioselectivities (up 99% yield 98% ee), which provides efficient access valuable molecules containing 3-hydroxy-2-oxindole core. The gram-scale reaction proved the potential utility methodology.

Language: Английский

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Access to Alkenyl Cyclobutanols by Ni‐Catalyzed Regio‐ and Enantio‐selective syn‐Hydrometalative 4‐exo‐trig Cyclization of Alkynones

Angewandte Chemie, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 12, 2024

Abstract Enantioselective synthesis of (spiro)cyclobutane derivatives poses significant challenges yet holds promising applications for both synthetic and medicinal chemistry. We report here a nickel‐catalyzed asymmetric syn ‐hydrometalative 4‐ exo ‐ trig cyclization 1,4‐alkynones to synthesize alkenyl cyclobutanols with tetrasubstituted stereocenter. This strategy features broad substrate scope, delivering variety trifluoromethyl‐containing rigid (spiro)carbocycle skeletons in good yields high enantioselectivities (up 84 % yield 98.5 : 1.5 er). The utility is demonstrated through stereospecific transformations into fused spiro molecules. Experimental computational mechanistic studies indicate that the reaction initiated by an active Ni−H species, carbonyl‐directed hydrometalation as key regioselective control. catalytic method provides general solution hydrofunctionalization alkynes represents efficient pattern assembling highly strained enantioenriched bioisosteres.

Language: Английский

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Recent Advances in Radical Reactions of 1,n‐Enynes with Phosphorus‐Centered Radicals

ChemistrySelect, Journal Year: 2024, Volume and Issue: 9(42)

Published: Nov. 1, 2024

Abstract Organophosphorus compounds have been widely used as achiral and chiral ligands in organic synthesis (PPh 3 , BINAP, dppe, Duphos, Xantphos, PPFA, Chiraphos, SEGPHOS), flame retardants, functional materials (LED, PV), well agrochemicals medicines due to their broad biological activities. As the privileged versatile building blocks, 1,n‐enynes successfully applied of various functionalized cyclic based on two active unsaturated chemical bonds (C═C double C≡C triple bonds). With development highly selective efficient methods chemistry, organophosphorus through radical cascade strategy has attracted considerable attention recent years. In here, we summarized main achievements reactions with phosphorus‐centered radicals. Furthermore, also displayed detailed reaction mechanisms this review.

Language: Английский

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