Organopalladium Catalysis as a Proving Ground for Data-Rich Approaches to Reaction Development and Quantitative Predictions DOI Creative Commons

Jingru Lu,

David C. Leitch

Published: Oct. 11, 2023

With the advent of high-throughput methods for both computation and experimentation, data-rich approaches to discovering understanding chemical reactions are becoming ever more central catalysis research. Organopalladium is at forefront these new approaches, providing a rich proving ground method development validation. This critical Perspective discusses number recent case studies from academic industrial laboratories that illustrate how generate, analyze, correlate large data sets quantitative predictions reactivity selectivity. Both power potential pitfalls discussed, as opportunities practical fundamental mechanistic insights.

Language: Английский

Synthetic Advantages of Defluorinative C−F Bond Functionalization DOI Creative Commons
Leidy V. Hooker, Jeffrey S. Bandar

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Aug. 22, 2023

Abstract Much progress has been made in the development of methods to both create compounds that contain C−F bonds and functionalize bonds. As such, are becoming common versatile synthetic functional handles. This review summarizes advantages defluorinative functionalization reactions for small molecule synthesis. The coverage is organized by type carbon framework fluorine attached mono‐ polyfluorinated motifs. main challenges, opportunities advances discussed each class organofluorine. Most text focuses on case studies illustrate how defluorofunctionalization can improve routes targets or properties enable unique mechanisms reactions. broader goal showcase incorporating exploiting design routes, improvement specific advent new methods.

Language: Английский

Citations

60
Photogeneration of α-Bimetalloid Radicals via Selective Activation of Multifunctional C1 Units DOI Creative Commons

Lewis McGhie,

Alessandro Marotta,

Patrick O. Loftus

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(23), P. 15850 - 15859

Published: May 28, 2024

Light-driven strategies that enable the chemoselective activation of a specific bond in multifunctional systems are comparatively underexplored comparison to transition-metal-based technologies, yet desirable when considering controlled exploration chemical space. With current drive discover next-generation therapeutics, reaction design enables strategic incorporation an sp3 carbon center, containing multiple synthetic handles for subsequent space would be highly enabling. Here, we describe photoactivation ambiphilic C1 units generate α-bimetalloid radicals using only Lewis base and light source directly activate C–I bond. Interception these transient with various SOMOphiles rapid synthesis organic scaffolds (B, Si, Ge) orthogonal activation. In-depth theoretical mechanistic studies reveal prominent role 2,6-lutidine forming photoactive charge transfer complex stabilizing situ generated iodine radicals, as well influential boron p-orbital activation/weakening This simple efficient methodology enabled expedient access functionalized 3D frameworks can further derivatized available technologies C–B C–Si

Language: Английский

Citations

14
Oxidative Addition of (Hetero)aryl (Pseudo)halides at Palladium(0): Origin and Significance of Divergent Mechanisms DOI
Matthew J. Kania, Albert Reyes, Sharon R. Neufeldt

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(28), P. 19249 - 19260

Published: July 3, 2024

Two limiting mechanisms are possible for oxidative addition of (hetero)aryl (pseudo)halides at Pd(0): a 3-centered concerted and nucleophilic displacement mechanism. Until now, there has been little understanding about when each mechanism is relevant. Prior investigations to distinguish between these pathways were limited few specific combinations the substrate ligand. Here, we computationally evaluated over 180 transition structures in order determine mechanistic trends based on substrate, ligand(s), coordination number. Natural abundance

Language: Английский

Citations

10
Catalyst-Controlled Enantioselective and Regiodivergent Addition of Aryl Boron Nucleophiles to N-Alkyl Nicotinate Salts DOI
Kacey G. Ortiz,

Jordan J. Dotson,

Donovan J. Robinson

et al.

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

Citations

22
Enantiocovergent Cross-Coupling Reaction with 1,4-Dihydropyridine Derivatives via Photoinduced Nickel Catalysis DOI
Tongtong Li, Lifeng Luo, Xiaokai Cheng

et al.

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

Citations

9
C2-Selective Palladium-Catalyzed C–S Cross-Coupling of 2,4-Dihalopyrimidines DOI
Oliver D. Jackson, Albert Reyes, Collin D. Stein

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 19, 2025

Under most conditions, 2,4-dihalopyrimidines undergo substitution reactions at C4. Here we report that Pd(II) precatalysts supported by bulky N-heterocyclic carbene ligands uniquely effect C2-selective cross-coupling of 2,4-dichloropyrimidine with thiols. The regioselectivity this reaction stands in stark contrast to ∼1500 previously reported Pd-catalyzed cross-couplings favor C4 the absence other substituents on pyrimidine ring. Selectivity catalytic system herein is extremely sensitive structure precatalyst, largely due competing C4-selective nucleophilic aromatic substitution. C2-selectivity high 1° thiols and thiophenols, a range substituted dichloropyrimidines can be used. atypical selectivity transformation may facilitate diversity-oriented synthesis, as demonstrated for derivatives an antiviral agent. these C2─Cl cleavage not take place through typical oxidative addition pathway.

Language: Английский

Citations

1
Regioselective Suzuki–Miyarua Cross-Coupling for Substituted 2,4-Dibromopyridines Catalyzed by C3-Symmetric Tripalladium Clusters DOI

Zhixin He,

Meng Chen,

Yingrui Song

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: 90(5), P. 1895 - 1904

Published: Jan. 24, 2025

Multipalladium clusters possess peculiar structures and synergistic effects for reactivity selectivity. Herein, C3-symmetric tripalladium (1, 0.5 mol %) afford C2-regioselective SMCC of 2,4-dibromopyridine with phenylboronic acids or pinacol esters (C2:C4 up to 98:1), in contrast Pd(OAc)2 ligand-free conditions. In addition, similar C2-selectivity was achieved Sonogashira, Negishi, Kumada coupling reactions. This method highlights their powerful catalytic ability, exclusive C2-selectivity, broad substrate scope, efficient amplification, multiple ligand-exchange feasibility demonstrates that the conventional sites could be successfully regulated even reversed by catalysts.

Language: Английский

Citations

1
Recent advances in the application of ligands in palladium-catalyzed chemoselective coupling reactions at C–Br, C–OTf, and C–Cl sites DOI

Shan Shan Ng,

Wai Hang Pang,

On Ying Yuen

et al.

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 10(17), P. 4408 - 4436

Published: Jan. 1, 2023

This article presents a comprehensive analysis of the progress in palladium-catalyzed coupling reactions, with an emphasis on how ligand characteristics affect chemoselectivity aryl (pseudo)halides.

Language: Английский

Citations

14
Triflate‐Selective Suzuki Cross‐Coupling of Chloro‐ and Bromoaryl Triflates Under Ligand‐Free Conditions DOI Creative Commons

Grace M. Ibsen,

Vitor H. Menezes da Silva,

J. Cole Pettigrew

et al.

Chemistry - An Asian Journal, Journal Year: 2023, Volume and Issue: 18(9)

Published: March 25, 2023

In the absence of strong ancillary ligands such as phosphines or N-heterocyclic carbenes, palladium salts are selective for C-OTf cleavage in room-temperature Suzuki couplings chloroaryl triflates acetonitrile. Similar "ligand-free" conditions DMSO also promote triflate-selective coupling bromoaryl triflates. This triflate selectivity complements typical preference reaction bromides prior reports using phosphine ligands. DFT calculations and additional experimental evidence consistent with oxidative addition taking place at homogeneous, possibly mononuclear, anionic supported by a solvent molecule.

Language: Английский

Citations

10
Site-selective chemical reactions by on-water surface sequential assembly DOI Creative Commons
Anupam Prasoon, Xiaoqing Yu, Mike Hambsch

et al.

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

Published: Dec. 14, 2023

Controlling site-selectivity and reactivity in chemical reactions continues to be a key challenge modern synthetic chemistry. Here, we demonstrate the discovery of site-selective on water surface via sequential assembly approach. A negatively charged surfactant monolayer guides electrostatically driven, epitaxial, aligned reagent amino-substituted porphyrin molecules, resulting well-defined J-aggregated structure. This constrained geometry molecules prompts subsequent directional alignment perylenetetracarboxylic dianhydride reagent, enabling selective formation one-sided imide bond between reagent. Surface-specific in-situ spectroscopies reveal underlying mechanism dynamic interface that promotes multilayer growth product. The reaction is further demonstrated by three reversible irreversible reactions, such as imide-, imine-, 1, 3-diazole (imidazole)- bonds involving molecules. unique approach enables can bring on-water synthesis forefront organic

Language: Английский

Citations

9