Native Amides as Enabling Vehicles for Forging sp³–sp³ Architectures via Interrupted Deaminative Ni-Catalyzed Chain-Walking

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(7), С. 3869 - 3874

Опубликована: Фев. 8, 2023

Herein, we disclose an interrupted deaminative Ni-catalyzed chain-walking strategy that forges sp3-sp3 architectures at remote, yet previously unfunctionalized, methylene sp3 C-H sites enabled by the presence of native amides. This protocol is characterized its mild conditions and wide scope, including challenging substrate combinations. Site-selectivity can be dictated a judicious choice ligand, thus offering opportunity to enable bond formations are otherwise inaccessible in conventional events.

Язык: Английский

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Diversifying Amino Acids and Peptides via Deaminative Reductive Cross-Couplings Leveraging High-Throughput Experimentation

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(10), С. 5684 - 5695

Опубликована: Фев. 28, 2023

A deaminative reductive coupling of amino acid pyridinium salts with aryl bromides has been developed to enable efficient synthesis noncanonical acids and diversification peptides. This method transforms natural, commercially available lysine, ornithine, diaminobutanoic acid, diaminopropanoic alanines homologated derivatives varying chain lengths. Attractive features include ability transverse scales, tolerance pharma-relevant (hetero)aryls biorthogonal functional groups, the applicability beyond monomeric short macrocyclic peptide substrates. The success this work relied on high-throughput experimentation identify complementary reaction conditions that proved critical for achieving a broad scope range substrates including

Язык: Английский

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Recent Advances in Electron Donor‐Acceptor (EDA)‐Complex Reactions involving Quaternary Pyridinium Derivatives

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(10), С. 1538 - 1564

Опубликована: Март 6, 2023

Abstract Quaternary pyridinium compounds are valuable intermediates in organic synthesis, which have gained immense popularity the synthetic community. The application of transition metal or photoredox catalysis transforming quaternary into various C−C and C−X bonds is well established. A majority these methods require high temperatures, expansive catalysts, delicate conditions for successful execution. On other hand, use metal‐free photocatalysis‐free strategies constructing using derivatives has been sought‐after. In this context, electron‐donor‐acceptor (EDA)‐complex reactions emerged as a state‐of‐the‐art methodology, do not any photocatalyst their EDA‐complex photochemistry takes advantage electron‐acceptor ability derivatives, can quickly generate radical precursor via deaminative process. These newly generated useful several transformations. We hereby, review, discuss an area major progress mediated involving with mechanism, substrate scope, limitations. magnified image

Язык: Английский

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

Chemical Reviews, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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

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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Upgrading ketone synthesis direct from carboxylic acids and organohalides

Nature Communications, Год журнала: 2020, Номер 11(1)

Опубликована: Июль 3, 2020

Abstract The ketone functional group has a unique reactivity in organic chemistry and is associated with number of useful reactions. Catalytic methods for synthesis are continually being developed. Here, we report photoredox, nickel phosphoranyl radical synergistic cross-electrophile coupling commercially available chemicals, aromatic acids aryl/alkyl bromides. This allows concise highly functionalized ketones directly, without the preparation activated carbonyl intermediates or organometallic compounds, thus complements conventional Weinreb synthesis. Use appropriate photocatalyst, ligand amount solvents can match reaction rate required by any simple catalytic cycle. practicality synthetic robustness illustrated facile complex from readily feedstock chemicals.

Язык: Английский

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Visible-Light-Induced Deaminative Thioesterification of Amino Acid Derived Katritzky Salts via Electron Donor–Acceptor Complex Formation

Organic Letters, Год журнала: 2019, Номер 21(21), С. 8673 - 8678

Опубликована: Окт. 22, 2019

A visible-light-mediated deaminative thioesterification of amino acid derived Katritzky salts with thiobenzoic has been developed, which provides a novel synthetic method for the synthesis α-mercapto derivatives under mild conditions. This photoredox catalyst-free generation alkyl radicals via C-N bond cleavage is enabled by formation an electron-donor-acceptor (EDA) complex between salt and anion, represents new entry EDA chemistry.

Язык: Английский

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Recent Methodologies That Exploit Oxidative Addition of C–N Bonds to Transition Metals

ACS Catalysis, Год журнала: 2020, Номер 10(21), С. 12738 - 12759

Опубликована: Окт. 19, 2020

The activation of σ-bonds by transition metals underpins a wide range methods for the synthesis complex molecules. Within this context, C–N bond has emerged recently as powerful strategy preparation or utilization nitrogen-containing compounds, due to prevalence bonds in organic compounds. A key challenge area is that most are relatively inert, and makes their difficult task. Since turn millennium number published articles regarding grown exponentially, providing important improvements methodologies such transformations. Indeed, several distinct strategies have been developed achieve activation. common exploited either strain release quaternization nitrogen center, while other state-of-the-art strategies, oxidative addition neutral use directing groups, also appeared. Despite considerable progress, deeper insight into mechanisms atom economy still required field advance. In Perspective we give an overview advances catalytic where achieved metals.

Язык: Английский

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Photoredox-Catalyzed Deaminative Alkylation via C–N Bond Activation of Primary Amines

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(43), С. 18310 - 18316

Опубликована: Окт. 15, 2020

Primary amines are often cheap, naturally occurring, and chemically diverse starting materials. For these reasons, deaminative functionalization of has emerged as an important area research. Recent advances in C-N activation transform simple α-1° α-2° into alkylating reagents via Katritzky pyridinium salts. We report a complementary method that activates sterically encumbered α-3° primary through visible light photoredox catalysis. By condensing with electron-rich aryl aldehyde, we enable oxidation deprotonation event, which generates key imidoyl radical intermediate. A subsequent β-scission event liberates alkyl radicals for coupling electron-deficient olefins the generation unnatural γ-quaternary amino acids other valuable synthetic targets.

Язык: Английский

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In-Situ Bromination Enables Formal Cross-Electrophile Coupling of Alcohols with Aryl and Alkenyl Halides

ACS Catalysis, Год журнала: 2021, Номер 12(1), С. 580 - 586

Опубликована: Дек. 21, 2021

Although alcohols are one of the largest pools alkyl substrates, approaches to utilize them in cross-coupling and cross-electrophile coupling limited. We report use 1° 2° with aryl vinyl halides form C(sp

Язык: Английский

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