Electrochemical Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(19), С. 11269 - 11335

Опубликована: Сен. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Язык: Английский

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Organothianthrenium salts: synthesis and utilization

Chemical Science, Год журнала: 2022, Номер 13(46), С. 13690 - 13707

Опубликована: Янв. 1, 2022

This review summarizes the synthesis of diverse organothianthrenium salts from various precursors and their applications in organic to forge new C–C, C–H C–heteroatom bonds by C–S bond cleavage with different mechanistic considerations.

Язык: Английский

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Asymmetric intermolecular allylic C–H amination of alkenes with aliphatic amines

Science, Год журнала: 2022, Номер 378(6625), С. 1207 - 1213

Опубликована: Дек. 15, 2022

Aliphatic allylic amines are found in a great variety of complex and biorelevant molecules. The direct C-H amination alkenes serves as the most straightforward method toward these motifs. However, use widely available internal with aliphatic this transformation remains synthetic challenge. In particular, palladium catalysis faces twin challenges inefficient coordination Pd(II) to but excessively tight therefore inhibitory by basic amines. We report general solution problems. developed protocol, contrast classical Pd(II/0) scenario, operates through blue light-induced Pd(0/I/II) manifold mild aryl bromide oxidant. This open-shell approach also enables enantio- diastereoselective amination.

Язык: Английский

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Allylic C–H amination cross-coupling furnishes tertiary amines by electrophilic metal catalysis

Science, Год журнала: 2022, Номер 376(6590), С. 276 - 283

Опубликована: Апрель 14, 2022

Intermolecular cross-coupling of terminal olefins with secondary amines to form complex tertiary amines-a common motif in pharmaceuticals-remains a major challenge chemical synthesis. Basic amine nucleophiles nondirected, electrophilic metal-catalyzed aminations tend bind and thereby inhibit metal catalysts. We reasoned that an autoregulatory mechanism coupling the release catalyst turnover could enable functionalization without inhibiting metal-mediated heterolytic carbon-hydrogen cleavage. Here, we report palladium(II)-catalyzed allylic amination using this strategy, featuring 48 cyclic acyclic (10 pharmaceutically relevant cores) 34 (bearing functionality) furnish 81 amines, including 12 drug compounds 10 derivatives, excellent regio- stereoselectivity (>20:1 linear:branched, >20:1 E:Z).

Язык: Английский

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Electrocatalytic Access to Azetidines via Intramolecular Allylic Hydroamination: Scrutinizing Key Oxidation Steps through Electrochemical Kinetic Analysis

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(28), С. 15360 - 15369

Опубликована: Июль 10, 2023

Azetidines are prominent structural scaffolds in bioactive molecules, medicinal chemistry, and ligand design for transition metals. However, state-of-the-art methods cannot be applied to intramolecular hydroamination of allylic amine derivatives despite their underlying potential as one the most prevalent synthetic precursors azetidines. Herein, we report an electrocatalytic method sulfonamides access azetidines first time. The merger cobalt catalysis electricity enables regioselective generation key carbocationic intermediates, which could directly undergo C-N bond formation. mechanistic investigations including electrochemical kinetic analysis suggest that either catalyst regeneration by nucleophilic cyclization or second oxidation intermediate is involved rate-determining step (RDS) our protocol highlight ability electrochemistry providing ideal means mediate oxidation.

Язык: Английский

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Unified metal-free intermolecular Heck-type sulfonylation, cyanation, amination, amidation of alkenes by thianthrenation

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 15, 2024

Abstract Direct and site-selective C-H functionalization of alkenes under environmentally benign conditions represents a useful attractive yet challenging transformation to access value-added molecules. Herein, unified protocol for variety intermolecular Heck-type functionalizations C sp2 -H bond has been developed by thianthrenation. The reaction features metal-free operationally simple exclusive cine -selective aliphatic aryl forge C-C, C-N, C-P, C-S bonds at room temperature, providing general with nucleophiles (Nu = sulfinates, cyanides, amines, amides). Alkenes undergo -sulfonylation, cyanation, amination afford alkenyl sulfones, nitriles enamines.

Язык: Английский

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1,4‐Aminoarylation of Butadienes via Photoinduced Palladium Catalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(14)

Опубликована: Фев. 9, 2024

Abstract A visible‐light‐induced, three‐component palladium‐catalyzed 1,4‐aminoarylation of butadienes with readily available aryl halides and aliphatic amines has been developed, affording allylamines excellent E ‐selectivity. The reaction exhibits exceptional control over chemo‐, regio‐, stereoselectivity, a broad substrate scope, high functional group compatibility, as demonstrated by the late‐stage functionalization bioactive molecules. Mechanistic investigations are consistent photoinduced radical Pd(0)‐Pd(I)‐Pd(II)‐Pd(0) Heck‐Tsuji–Trost allylation cascade.

Язык: Английский

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Adoption of Electrochemistry within the Pharmaceutical Industry: Insights from an Industry-Wide Survey

Organic Process Research & Development, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Язык: Английский

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Photoredox-Catalyzed α-Sulfonylation of Ketones from Sulfur Dioxide and Thianthrenium Salts

Organic Letters, Год журнала: 2022, Номер 24(15), С. 2955 - 2960

Опубликована: Апрель 13, 2022

A photoredox-catalyzed sulfonylation of silyl enol ethers with DABCO·(SO2)2 and thianthrenium salts is achieved, providing diverse β-keto sulfones in moderate to good yields. This protocol features easily accessible starting materials functional group compatibility, enabling the introduction various functionalized sulfonyl groups into ketones. Furthermore, as one important industrial raw materials, methanol can be employed methyl source prepare α-methylsulfonated ketones through a intermediate for first time.

Язык: Английский

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Site-selective amination towards tertiary aliphatic allylamines

Nature Catalysis, Год журнала: 2022, Номер 5(7), С. 642 - 651

Опубликована: Июль 22, 2022

Язык: Английский

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