Cross-Electrophile Coupling: Principles, Methods, and Applications in Synthesis

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

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Computational Methods Enable the Prediction of Improved Catalysts for Nickel-Catalyzed Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(5), P. 3043 - 3051

Published: Jan. 26, 2024

Cross-electrophile coupling has emerged as an attractive and efficient method for the synthesis of C(sp2)–C(sp3) bonds. These reactions are most often catalyzed by nickel complexes nitrogenous ligands, especially 2,2′-bipyridines. Precise prediction, selection, design optimal ligands remains challenging, despite significant increases in reaction scope mechanistic understanding. Molecular parameterization statistical modeling provide a path to development improved bipyridine that will enhance selectivity existing broaden electrophiles can be coupled. Herein, we describe generation computational ligand library, correlation observed outcomes with features silico Ni-catalyzed cross-electrophile coupling. The new nitrogen-substituted display 5-fold increase product formation versus homodimerization when compared current state art. This yield was general several couplings, including challenging aryl chloride N-alkylpyridinium salt.

Language: Английский

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Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes

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

Published: Feb. 19, 2024

In contemporary drug discovery, enhancing the sp

Language: Английский

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Alkene Hydrobenzylation by a Single Catalyst That Mediates Iterative Outer-Sphere Steps

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2351 - 2357

Published: Jan. 17, 2024

Cross-coupling catalysts typically react and unite functionally distinct partners via sequential inner-sphere elementary steps: coordination, migratory insertion, reductive elimination, etc. Here, we report a single catalyst that cross-couples styrenes benzyl bromides iterative outer-sphere metal–ligand-carbon interactions. Each partner forms stabilized radical intermediate, yet heterocoupled products predominate. The system is redox-neutral and, thus, avoids exogenous oxidants, resulting in simple scalable conditions. Numerous variations of alkene hydrobenzylation are made possible, including access to the privileged heterodibenzyl (1,2-diarylethane) motif challenging quaternary carbon variants.

Language: Английский

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One-Pot Synthesis of Sulfonamides from Unactivated Acids and Amines via Aromatic Decarboxylative Halosulfonylation

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(39), P. 21189 - 21196

Published: Sept. 20, 2023

The coupling of carboxylic acids and amines to form amide linkages is the most commonly performed reaction in pharmaceutical industry. Herein, we report a new strategy that merges these traditional partners generate sulfonamides, important bioisosteres. This method leverages copper ligand-to-metal charge transfer (LMCT) convert aromatic sulfonyl chlorides, followed by one-pot amination corresponding sulfonamide. process requires no prefunctionalization native acid or amine extends diverse set aryl, heteroaryl, s-rich aliphatic substrates. Further, extend this synthesis (hetero)aryl fluorides, which have found utility as "click" handles chemical probes programmable bifunctional reagents. Finally, demonstrate protocols analogue synthesis.

Language: Английский

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Formation of C(sp²)–C(sp³) Bonds Instead of Amide C–N Bonds from Carboxylic Acid and Amine Substrate Pools by Decarbonylative Cross-Electrophile Coupling

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 9951 - 9958

Published: May 1, 2023

Carbon-heteroatom bonds, most often amide and ester are the standard method to link together two complex fragments because carboxylic acids, amines, alcohols ubiquitous reactions reliable. However, C-N C-O linkages a metabolic liability they prone hydrolysis. While C(sp

Language: Английский

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Rapid planning and analysis of high-throughput experiment arrays for reaction discovery

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 3, 2023

High-throughput experimentation (HTE) is an increasingly important tool in reaction discovery. While the hardware for running HTE chemical laboratory has evolved significantly recent years, there remains a need software solutions to navigate data-rich experiments. Here we have developed phactor™, that facilitates performance and analysis of laboratory. phactor™ allows experimentalists rapidly design arrays reactions or direct-to-biology experiments 24, 96, 384, 1,536 wellplates. Users can access online reagent data, such as inventory, virtually populate wells with produce instructions perform array manually, assistance liquid handling robot. After completion array, analytical results be uploaded facile evaluation, guide next series All metadata, are stored machine-readable formats readily translatable various software. We also demonstrate use discovery several chemistries, including identification low micromolar inhibitor SARS-CoV-2 main protease. Furthermore, been made available free academic 24- 96-well via interface.

Language: Английский

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A decarbonylative approach to alkylnickel intermediates and C(sp ³ )-C(sp ³ ) bond formation

Science, Journal Year: 2024, Volume and Issue: 385(6715), P. 1331 - 1337

Published: Sept. 19, 2024

The myriad nickel-catalyzed cross-coupling reactions rely on the formation of an organonickel intermediate, but limitations in forming monoalkylnickel species have limited options for C(sp 3 ) cross-coupling. monoalkylnickel(II) from abundant carboxylic acid esters would be valuable, derivatives are primarily decarboxylated to form alkyl radicals that lack correct reactivity. In this work, we disclose a facile oxidative addition and decarbonylation sequence forms intermediates through nonradical process. key ligand, bis(4-methylpyrazole)pyridine, accelerates decarbonylation, stabilizes alkylnickel(II) destabilizes off-cycle nickel(0) carbonyl species. utility new reactivity )-C(sp bond is demonstrated reaction challenging by purely radical methods—the selective primary with iodides.

Language: Английский

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Persistent organonickel complexes as general platforms for Csp2–Csp3 coupling reactions

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(9), P. 1515 - 1522

Published: April 29, 2024

Language: Английский

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Ligand Relay for Nickel‐Catalyzed Decarbonylative Alkylation of Aroyl Chlorides

Advanced Science, Journal Year: 2023, Volume and Issue: 11(9)

Published: Dec. 13, 2023

Abstract Transition metal‐catalyzed direct decarboxylative transformations of aromatic carboxylic acids usually require high temperatures, which limit the substrate's scope, especially for late‐stage applications. The development selective decarbonylative acid derivatives, most fundamental aroyl chlorides, with stable and cheap electrophiles under mild conditions is highly desirable meaningful, but remains challenging. Herein, a strategy nickel‐catalyzed alkylation chlorides via phosphine/nitrogen ligand relay reported. simple phosphine found essential decarbonylation step, while nitrogen promotes cross‐electrophile coupling. Such system can effectively orderly carry out catalytic process at room temperature, utilizing easily available as an aryl electrophile reductive alkylation. This discovery provides new coupling, features operationally simple, conditions, excellent functional group tolerance. approach applied to methylation various pharmaceuticals. Extensive experiments are carried provide insights into reaction pathway support process.

Language: Английский

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