Ni-catalyzed enantioconvergent deoxygenative reductive cross-coupling of unactivated alkyl alcohols and aryl bromides

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 28, 2024

Abstract Transition metal-catalyzed enantioconvergent cross-coupling of an alkyl precursor presents a promising method for producing enantioenriched C(sp 3 ) molecules. Because alcohol is ubiquitous and abundant family feedstock in nature, the direct reductive coupling aryl halide enables efficient access to valuable compounds. Although several strategies have been developed overcome high bond dissociation energy C − O bond, asymmetric pattern remains unknown. In this report, we describe realization deoxygenative unactivated (β-hydroxy ketone) bromide presence NHC activating agent. The approach can accommodate substituents various sizes functional groups, its synthetic potency demonstrated through gram scale reaction derivatizations into other compound families. Finally, apply our convergent synthesis four β-aryl ketones that are natural products or bioactive

Language: Английский

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Dual Nickel- and Photoredox-Catalyzed Asymmetric Reductive Cross-Couplings: Just a Change of the Reduction System?

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(14), P. 1997 - 2011

Published: July 4, 2024

ConspectusIn recent years, nickel-catalyzed asymmetric coupling reactions have emerged as efficient methods for constructing chiral C(sp

Language: Английский

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Advances in silylation and borylation of fluoroarenes and gem-difluoroalkenes via C–F bond cleavage

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(90), P. 11922 - 11934

Published: Jan. 1, 2021

Organoboron and organosilane compounds are widely used in organic synthesis pharmaceuticals.

Language: Английский

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Nickel-catalyzed reductive cross-coupling of polyfluoroarenes with alkyl electrophiles by site-selective C–F bond activation

Chinese Chemical Letters, Journal Year: 2022, Volume and Issue: 33(9), P. 4287 - 4292

Published: Feb. 3, 2022

Language: Английский

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Asymmetric construction of allylicstereogenic carbon center featuring atrifluoromethyl group via enantioselective reductive fluoroalkylation

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Nov. 17, 2022

Abstract Emerging as a powerful tool for lead optimization in pharmaceutical research and development, to develop the facile, general protocols that allows incorporation of fluorine-containing motif drug candidates has accumulated enormous interest recent years. Among these important motifs, strategic CF 3 on aliphatic chain especially with concomitant construction trifluoromethylated alkanes bearing -substituted stereogenic carbon, is paramount importance. Herein, we disclose an asymmetric nickel-catalyzed reductive trifluoroalkylation alkenyl halides enantioselective syntheses diverse α -trifluoromethylated allylic alkanes, offering protocol access trifluoromethyl analogue chiral -methylated one most prevalent key components among natural products pharmaceuticals. Utilities method including application multiple biologically active complex molecules, derivatization transformable functionality were demonstrated, providing facile diversity-oriented -containing drugs bioactive-molecules.

Language: Английский

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Fe-Catalyzed Alkylazidation of α-Trifluoromethylalkenes: An Access to Quaternary Stereocenters Containing CF₃ and N₃ Groups

Organic Letters, Journal Year: 2023, Volume and Issue: 25(8), P. 1336 - 1341

Published: Feb. 23, 2023

A concise Fe-catalyzed alkylazidation of α-trifluoromethylalkenes via a C–C bond cleavage/radical addition/azidation cascade is described. This protocol features broad substrate scope, excellent functional group compatibility, and the ability to be performed on gram scale, thus offering practical step-economic approach synthetically useful tertiary α-trifluoromethyl azides.

Language: Английский

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Diverse Synthesis of Chiral Trifluoromethylated Alkanes via Nickel-Catalyzed Enantioconvergent Reductive Hydroalkylation of Unactivated Olefins

Organic Letters, Journal Year: 2022, Volume and Issue: 24(9), P. 1796 - 1801

Published: March 2, 2022

Here, we report a nickel-catalyzed enantioconvergent hydroalkylation of olefins with trifluoromethyl-containing α-alkyl halides for the synthesis enantioenriched trifluoromethylated alkanes. This reaction employs readily available and bench-stable alkenes as alkyl coupling partners, featuring mild conditions, broad substrate scope, high functional group tolerance. The synthetic utility this method is further demonstrated in late-stage functionalization range drug molecules natural products.

Language: Английский

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Nickel-Catalyzed Cross-Coupling of Acyl Chloride with Racemic α-Trifluoromethyl Bromide to Access Chiral α-Trifluoromethyl Ketones

Organic Letters, Journal Year: 2022, Volume and Issue: 24(24), P. 4322 - 4327

Published: June 10, 2022

The nickel-catalyzed reductive cross-coupling reaction of acyl chloride with racemic secondary α-trifluoromethyl bromide has been developed. By this chemistry, a series structurally interesting chiral α-CF3 carbonyl compounds could be accessed great enantioselectivity and good functional group tolerance. study late-stage transformation indicated that chemistry used as the robust method to prepare products contain bioactive motif. Furthermore, importance illustrated by control experiments.

Language: Английский

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A General Copper‐Box System for the Asymmetric Arylative Functionalization of Benzylic, Propargylic or Allenylic Radicals

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

Published: July 27, 2024

Abstract Radical‐involved arylative cross‐coupling reactions have recently emerged as an attractive strategy to access valuable aryl‐substituted motifs. However, there still exist several challenges such limited scope of radical precursors/acceptors, and lack general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a copper‐Box system for three‐component vinylarenes 1,3‐enynes, with oxime carbonates aryl boronic acids. The proceed under practical conditions in absence or presence visible‐light irradiation, affording chiral 1,1‐diarylalkanes, benzylic alkynes allenes good enantioselectivities. Mechanistic studies imply that copper/Box complexes play dual role both generation ensuing cross‐coupling. In cases irradiation could improve activity complex toward initial generation, enabling better efficiency match between formation

Language: Английский

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CF2H-synthon enables asymmetric radical difluoroalkylation for synthesis of chiral difluoromethylated amines

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

Published: Jan. 11, 2025

The difluoromethyl group is a crucial fluorinated moiety with distinctive biological properties, and the synthesis of chiral CF₂H-containing analogs has been recognized as powerful strategy in drug design. To date, most established method for accessing enantioenriched compounds involves enantioselective functionalization nucleophilic electrophilic CF₂H synthons. However, this approach limited by lower reactivity reduced enantioselectivity. Leveraging unique fluorine effect, we design synthesize radical synthon incorporating isoindolinone into alkyl halides asymmetric transformation. Here, report an efficient construction carbon stereocenters featuring via nickel-catalyzed Negishi cross-coupling. This demonstrates mild reaction conditions excellent Given that optically pure difluoromethylated amines isoindolinones are key structural motifs bioactive compounds, offers practical solution drug-like molecules. moiety, screening. authors

Language: Английский

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