Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dichloroheteroarenes under Ligand-Controlled and Ligand-Free Systems

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(11), P. 7414 - 7421

Published: May 18, 2022

Halides adjacent to nitrogen are conventionally more reactive in Pd-catalyzed cross-couplings of dihalogenated N-heteroarenes. However, a very sterically hindered N-heterocyclic carbene ligand is shown promote room-temperature cross-coupling at C4 2,4-dichloropyridines with high selectivity (∼10:1). This work represents the first highly selective method broad scope for C4-coupling these substrates where clearly under control. Under optimized conditions, diverse substituted and related compounds undergo form C4–C(sp2) C4–C(sp3) bonds using organoboron, -zinc, -magnesium reagents. The synthetic utility this highlighted multistep syntheses that combine C4-selective subsequent nucleophilic aromatic substitution reactions. majority products herein (71%) have not been previously reported, emphasizing ability methodology open up underexplored chemical space. Remarkably, we find ligand-free "Jeffery" conditions enhance Suzuki coupling by an order magnitude (>99:1). These enable C5-selective 2,5-dichloropyridine 2,5-dichloropyrimidine.

Language: Английский

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Catalyst-Controlled Enantioselective and Regiodivergent Addition of Aryl Boron Nucleophiles to N-Alkyl Nicotinate Salts

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(21), P. 11781 - 11788

Published: May 19, 2023

Dihydropyridines are versatile building blocks for the synthesis of pyridines, tetrahydropyridines, and piperidines. Addition nucleophiles to activated pyridinium salts allows 1,2-, 1,4-, or 1,6-dihydropyridines; however, this process often leads a mixture constitutional isomers. Catalyst-controlled regioselective addition pyridiniums has potential solve problem. Herein, we report that boron-based can be accomplished by choice Rh catalyst.

Language: Английский

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Machine Learning-Guided Development of Trialkylphosphine Ni^(I) Dimers and Applications in Site-Selective Catalysis

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(28), P. 15414 - 15424

Published: July 6, 2023

Owing to the unknown correlation of a metal’s ligand and its resulting preferred speciation in terms oxidation state, geometry, nuclearity, rational design multinuclear catalysts remains challenging. With goal accelerate identification suitable ligands that form trialkylphosphine-derived dihalogen-bridged Ni(I) dimers, we herein employed an assumption-based machine learning approach. The workflow offers guidance space for desired without (or only minimal) prior experimental data points. We experimentally verified predictions synthesized numerous novel dimers as well explored their potential catalysis. demonstrate C–I selective arylations polyhalogenated arenes bearing competing C–Br C–Cl sites under 5 min at room temperature using 0.2 mol % newly developed dimer, [Ni(I)(μ-Br)PAd2(n-Bu)]2, which is so far unmet with alternative dinuclear or mononuclear Ni Pd catalysts.

Language: Английский

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Enantiocovergent Cross-Coupling Reaction with 1,4-Dihydropyridine Derivatives via Photoinduced Nickel Catalysis

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(5), P. 3278 - 3286

Published: Feb. 15, 2024

Herein, we reported the enantioconvergent Csp3–Csp2 cross-coupling reaction with 1,4-dihydropyridine (DHP) derivatives via photoredox/nickel dual catalysis to access chiral products good yield and enantioselectivity. The operationally simple was carried out under mild conditions functional group tolerance. Due use of a stoichiometric equivalent aryl/alkenyl halides as coupling partners, sequential iterative synthesis could be achieved smoothly in one pot for position isomers stereoisomers. In proposed mechanism, kinetic experiments mechanistic studies indicated that radical generation, depended on excited photocatalyst DHP, rate-determining step.

Language: Английский

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Visible‐Light‐Mediated Photocatalyst‐Free Hydroacylation of Azodicarboxylic Acid Derivatives with 4‐Acyl‐1,4‐dihydropyridines

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: 42(11), P. 1230 - 1236

Published: Feb. 5, 2024

Comprehensive Summary A visible‐light‐enabled, photocatalyst‐free hydroacylation reaction of azodicarboxylic acid derivatives was described. This radical conjugate addition (RCA) protocol relied on the dual role 4‐acyl‐1,4‐dihydropyridine (acyl‐DHP) reagents that besides being as reservoirs, they also enabled conversion adducts to anion intermediates via reduction. Under “catalyst‐oxidant‐additive free” conditions, a wide range structurally different acyl hydrazide products were readily obtained in 56%—99% yields. The utility this transformation further demonstrated by scale‐up synthesis and downstream derivatization.

Language: Английский

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The Road Less Traveled: Unconventional Site Selectivity in Palladium-Catalyzed Cross-Couplings of Dihalogenated N-Heteroarenes

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(19), P. 12014 - 12026

Published: Sept. 19, 2022

The vast majority (≥90%) of literature reports agree on the regiochemical outcomes Pd-catalyzed cross-coupling reactions for most classes dihalogenated N-heteroarenes. Despite a well-established mechanistic rationale typical selectivity, several examples reveal that changes to catalyst can switch site leading unconventional product. In this Perspective, we survey these unusual cases in which divergent selectivity is controlled by ligands or speciation. some cases, origin inverted has been established, but others mechanism remains unknown. This Perspective concludes with discussion remaining challenges and opportunities field site-selective cross-coupling. These include developing better understanding oxidative addition mechanisms, role speciation establishing an explanation influence ring substituents outcome, inverting "stubborn" substrates, minimizing unwanted over-reaction di- polyhalogenated substrates.

Language: Английский

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Recent progress in the oxidative bromination of arenes and heteroarenes

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(8), P. 1571 - 1590

Published: Jan. 1, 2023

This review summarizes recent developments in the field of oxidative preparation bromoarenes and bromoheteroarenes covering from 2012 to 2022.

Language: Английский

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Nickel‐Catalyzed C−I‐Selective C(sp²)−C(sp³) Cross‐Electrophile Coupling of Bromo(iodo)arenes with Alkyl Bromides

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(26)

Published: May 4, 2023

Despite several methodologies established for C(sp2 )-I selective )-C(sp3 ) bond formations, achieving arene-flanked quaternary carbons by cross-coupling of tertiary alkyl precursors with bromo(iodo)arenes in a manner is rare. Here we report general Ni-catalyzed cross-electrophile coupling (XEC) reaction, which, beyond 3° bromides (for constructing carbons), 2° and 1° are also demonstrated to be viable partners. Moreover, this mild XEC displays excellent selectivity functional group compatibility. The practicality simplifying the routes medicinally relevant synthetically challenging compounds. Extensive experiments show that terpyridine-ligated NiI halide can exclusively activate bromides, forming -alkyl complex through Zn reduction. Attendant density theory (DFT) calculations reveal two different pathways oxidative addition bromo(iodo)arenes, explaining both high generality our XEC.

Language: Английский

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Electrocatalytic dehalogenation in the applications of organic synthesis and environmental degradation

EcoEnergy, Journal Year: 2024, Volume and Issue: 2(1), P. 83 - 113

Published: Feb. 26, 2024

Abstract Electrocatalytic dehalogenation technology is a promising approach for the synthesis of chemicals (such as pesticides and pharmaceutical intermediates) disposal halogenated organic pollutants. Compared with traditional chemical reduction technology, electrocatalytic method has advantages high efficiency, controllable operation, reduced secondary pollution. This review systematically consolidates recent advances in application environmental degradation, focusing on involved mechanisms, influences factors (e.g., electrocatalysts, solution environment, reaction conditions) performance dehalogenation. Furthermore, latest characterization analytical methods industrial are summarized. Lastly, existing challenges perspectives proposed efficient

Language: Английский

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Mechanisms and Site Selectivity of (Het)Ar–X Oxidative Addition to Pd(0) Are Controlled by Frontier Molecular Orbital Symmetry

Published: May 28, 2024

We report how the reaction mechanism and site-selectivity of 2-halopyridine oxidative addition to L2Pd(0) are both controlled by frontier molecular orbital symmetry. Comparing rates for pairs 2-chloro-3-EDG-pyridines / 2-chloro-5-EDG-pyridines (EDG = electron-donating group: NH2, OMe F) Pd(PCy3)2 reveals 3-EDG isomers undergo ~100 times faster than their 5-EDG counterparts (∆ΔG‡OA 10.4-11.6 kJ mol-1). Experimental computational mechanistic studies reveal that LUMO symmetries substrates control mechanism. For derivatives, high coefficients at reactive C2 position, antibonding symmetry through C2=N bond pyridine lead a nucleophilic displacement oxida-tive Conversely, derivatives has node C5–C2 plane, lead-ing minimal contribution carbon. The higher energy LUMO+1 substantial density C2, but nitrogen. This leads undergoing 3-centered insertion These effects also multihalogenated pyridines, which we investigate electron-withdrawing substituents. Incorporating simple fron-tier based descriptors quantitative multivariate linear model im-proved prediction accuracy relative substituted L2Pd(0).

Language: Английский

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