Dynamic Kinetic Cross-Electrophile Arylation of Benzyl Alcohols by Nickel Catalysis

Journal of the American Chemical Society, Год журнала: 2020, Номер 143(1), С. 513 - 523

Опубликована: Дек. 28, 2020

Catalytic transformation of alcohols via metal-catalyzed cross-coupling reactions is very important, but it typically relies on a multistep procedure. We here report dynamic kinetic approach for the direct functionalization alcohols. The feasibility this strategy demonstrated by nickel-catalyzed cross-electrophile arylation reaction benzyl with (hetero)aryl electrophiles. proceeds broad substrate scope both coupling partners. electron-rich, electron-poor, and ortho-/meta-/para-substituted electrophiles (e.g., Ar–OTf, Ar–I, Ar–Br, inert Ar–Cl) all coupled well. Most functionalities, including aldehyde, ketone, amide, ester, nitrile, sulfone, furan, thiophene, benzothiophene, pyridine, quinolone, Ar–SiMe3, Ar–Bpin, Ar–SnBu3, were tolerated. nature method enables benzylic alcohol in presence various nucleophilic groups, nonactivated primary/secondary/tertiary alcohols, phenols, free indoles. It thus offers robust alternative to existing methods precise construction diarylmethanes. synthetic utility was concise synthesis biologically active molecules its application peptide modification conjugation. Preliminary mechanistic studies revealed that situ formed oxalates nickel, possibly radical process, an initial step aryl

Язык: Английский

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Nickel‐Catalyzed Synthesis of Dialkyl Ketones from the Coupling of N‐Alkyl Pyridinium Salts with Activated Carboxylic Acids

Angewandte Chemie International Edition, Год журнала: 2020, Номер 59(32), С. 13484 - 13489

Опубликована: Май 6, 2020

Abstract While ketones are among the most versatile functional groups, their synthesis remains reliant upon reactive and low‐abundance starting materials. In contrast, amide formation is most‐used bond‐construction method in medicinal chemistry because reliable draws large diverse substrate pools. A new for of presented here that from same substrates used bond synthesis: amines carboxylic acids. nickel terpyridine catalyst couples N‐alkyl pyridinium salts with situ formed acid fluorides or 2‐pyridyl esters under reducing conditions (Mn metal). The reaction has a broad scope, as demonstrated by 35 different bearing wide variety groups an average yield 60±16 %. This approach capable coupling substrates, including pharmaceutical intermediates, to rapidly form complex ketones.

Язык: Английский

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Oriented External Electric Fields and Ionic Additives Elicit Catalysis and Mechanistic Crossover in Oxidative Addition Reactions

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(8), С. 3836 - 3850

Опубликована: Янв. 29, 2020

Judiciously applied oriented external electric fields (OEEFs) exert catalytic effects on the kinetics and improve thermodynamics of chemical reactions. Herein, we examine ability OEEFs to assist catalysts show that rate oxidative addition between palladium alkyl/aryl electrophiles can be controlled by an OEEF along direction electron reorganization (the "reaction axis"). The concerted mechanism proceeds through a transition state with moderate charge transfer character. We demonstrate reaction axis control this impart electrostatic catalysis. When field exceeds certain critical value (∼0.15 V/Å), observed mechanistic crossover from dissociative CSNAr type reactivity for aryl electrophiles. To our surprise, alkyl follow hitherto unexplored SN2 pathway large stabilization at relatively low OEEFs. A valence-bond correlation diagram (VBSCD) is employed comprehend results. Finally, although effect salt additives in known, its still under debate. Our findings further evidence electric-field cross-coupling reactions, their cocatalytic judiciously reproduced fields. As such, propose use (anionic or cationic) experimentally viable strategy implement routinely used

Язык: Английский

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Sulfonate Versus Sulfonate: Nickel and Palladium Multimetallic Cross-Electrophile Coupling of Aryl Triflates with Aryl Tosylates

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(24), С. 10634 - 10640

Опубликована: Июнь 2, 2020

While phenols are frequent and convenient aryl sources in cross-coupling, typically as sulfonate esters, the direct cross-Ullmann coupling of two different esters is unknown. We report here a general solution to this challenge catalyzed by combination Ni Pd with Zn reductant LiBr an additive. The reaction has broad scope, demonstrated 33 examples (65% ± 11% average yield). Mechanistic studies show that strongly prefers triflate, catalyst small preference for tosylate, transfer between catalysts mediated Zn, improves yields consuming arylzinc intermediates.

Язык: Английский

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Ni-Catalyzed Reductive Cyanation of Aryl Halides and Phenol Derivatives via Transnitrilation

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(49), С. 19257 - 19262

Опубликована: Ноя. 11, 2019

Herein, we report a Ni-catalyzed reductive coupling for the synthesis of benzonitriles from aryl (pseudo)halides and an electrophilic cyanating reagent, 2-methyl-2-phenyl malononitrile (MPMN). MPMN is bench-stable, carbon-bound CN reagent that does not release cyanide under reaction conditions. A variety medicinally relevant can be made in good yields. Addition NaBr to mixture allows use more challenging electrophiles such as chlorides, tosylates, triflates. Mechanistic investigations suggest plays role facilitating oxidative addition with these substrates.

Язык: Английский

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Nickel-Catalyzed Reductive Carboxylation and Amidation Reactions

Accounts of Chemical Research, Год журнала: 2021, Номер 54(20), С. 3941 - 3952

Опубликована: Сен. 29, 2021

ConspectusThe ubiquity and importance of carboxylic acids amides in peptides, pharmaceuticals, agrochemicals, synthetic materials has challenged chemists to design de novo catalytic carboxylation amidation protocols. They represent a powerful alternative canonical oxidation alcohols aldehydes, hydrolysis nitriles, transamidation reactions, or condensation techniques for the synthesis these functional groups. Among various scenarios, recent years have witnessed considerable advances Ni-catalyzed reductive reactions utilizing carbon dioxide isocyanate counterparts. This Account aims highlight progress made this arena with historical perspective, particular emphasis on methodologies that emanated from our laboratories without losing sight underlying principles by which operate, ultimate goal allowing transition comprehension prediction exciting field.Unlike utilization conventional polar yet highly reactive organometallic reagents nickel catalysts allowed use isocyanates less less-polarized counterparts formations amides. These groups include organic halides pseudohalides (i.e., alkyl bromides chlorides, esters, alcohols, ammonium salts), unsaturated hydrocarbons alkynes, styrenes, unactivated alkenes, dienes) even C–H bonds, where forging targeted C–C bond at previously unfunctionalized linkages was possible, thus giving access densely functionalized compounds would be difficult otherwise. The functionalization includes chain-walking subtle changes ligand reaction conditions marked selectivity transformations, via [1,4]-Ni shift, selective aromatic rings could achieved. Conceptuality practicality aside, transformations offered possibility modulating dictating site-selectivity pattern, providing not only new vistas when controlling bond-forming specific sites within side chain but also knowledge retrosynthetic analysis accessing amide backbones. Importantly, shown particularly suited preparation isotopically labeled molecules using 13CO2 14CO2, becoming useful endeavor drug discovery pipeline. Although mechanistic understanding molecular level still constitutes "Achilles heel" empirical discoveries rapid adoption protocols community augurs well widespread both academic industrial laboratories.

Язык: Английский

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Chemodivergence between Electrophiles in Cross‐Coupling Reactions

Chemistry - A European Journal, Год журнала: 2020, Номер 27(20), С. 6161 - 6177

Опубликована: Ноя. 18, 2020

Chemodivergent cross-couplings are those in which either one of two (or more) potentially reactive functional groups can be made to react based on choice conditions. In particular, this review focuses involving different (pseudo)halides that compete for the role electrophilic coupling partner. The discussion is primarily organized by pairs electrophiles including chloride vs. triflate, bromide tosylate, and halide halide. Some common themes emerge regarding origin selectivity control. These include catalyst ligation state solvent polarity or coordinating ability. However, many cases, further systematic studies will necessary deconvolute influences metal identity, ligand, solvent, additives, nucleophilic partner, other factors chemoselectivity.

Язык: Английский

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Chemoselective Cross-Coupling between Two Different and Unactivated C(aryl)–O Bonds Enabled by Chromium Catalysis

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(17), С. 7715 - 7720

Опубликована: Апрель 17, 2020

We report here the first example of cross-coupling between two different and unactivated C(aryl)–O bonds with chromium catalysis. The combination a low-cost Cr(II) salt, 4,4′-di-tert-butyl-2,2′-dipyridyl (dtbpy) as ligand, magnesium reductant shows high reactivity in promoting reductive aryl methyl ether derivatives esters by cleavage coupling under mild conditions. formation active low-valent Cr species reduction CrCl2 Mg can be considered, which prefers to initially activate bond phenyl chelation help dtbpy an o-imine auxiliary. subsequent consecutive reduction, second activation, elimination allow for achievement selective C(aryl)–O/C(aryl)–O bonds.

Язык: Английский

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Ni-Catalyzed Aryl Sulfide Synthesis through an Aryl Exchange Reaction

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(27), С. 10333 - 10340

Опубликована: Июнь 28, 2021

A Ni-catalyzed aryl sulfide synthesis through an exchange reaction between sulfides and a variety of electrophiles was developed. By using 2-pyridyl as donor, this achieved the without odorous toxic thiols. The use Ni/dcypt catalyst capable cleaving forming aryl–S bonds important for electrophiles, which include aromatic esters, arenol derivatives, halides. Mechanistic studies revealed that can simultaneously undergo oxidative additions followed by ligand generated aryl–Ni–SR aryl–Ni–OAr species to furnish exchanged compounds.

Язык: Английский

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Stereoselective gem-Difluorovinylation of gem-Difluorinated Cyclopropanes Enabled by Ni/Pd Cooperative Catalysis

ACS Catalysis, Год журнала: 2021, Номер 11(19), С. 11960 - 11965

Опубликована: Сен. 13, 2021

A cross-electrophile coupling between gem-difluorinated cyclopropanes and 2,2-difluorovinyl tosylate via dual Ni/Pd cooperative catalysis under mild reaction conditions is presented. Various structurally unique organofluorine compounds bearing both monofluoroalkene gem-difluoroalkene moieties can be effectively afforded in good yields with a high (Z)-selectivity. The synthetic utility of this protocol has been successfully demonstrated by the late-stage modification series complex bioactive molecules.

Язык: Английский

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