Installing the “magic methyl” – C–H methylation in synthesis

Chemical Society Reviews, Год журнала: 2021, Номер 50(9), С. 5517 - 5563

Опубликована: Янв. 1, 2021

Following notable cases of remarkable potency increases in methylated analogues lead compounds, this review documents the state-of-the-art C–H methylation technology.

Язык: Английский

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C(sp ³ )–H methylation enabled by peroxide photosensitization and Ni-mediated radical coupling

Science, Год журнала: 2021, Номер 372(6540), С. 398 - 403

Опубликована: Апрель 22, 2021

Adding methyl groups with good timing In pharmaceutical research, swapping out hydrogens for is a frequent strategy to optimize small-molecule properties. Vasilopoulos et al. report versatile, convenient, and comparatively safe method methylation of carbon centers adjacent nitrogen or aryl rings. Under carefully optimized conditions, di-tert-butyl peroxide plays dual role as oxidant source. Cleaving the O–O bond through photosensitization produces butoxyl radicals, some which cleave substrate C–H bonds, whereas others release radicals that nickel catalyst delivers those activated substrates. Science , this issue p. 398

Язык: Английский

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Enzymatic Late‐Stage Modifications: Better Late Than Never

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(31), С. 16824 - 16855

Опубликована: Янв. 16, 2021

Enzyme catalysis is gaining increasing importance in synthetic chemistry. Nowadays, the growing number of biocatalysts accessible by means bioinformatics and enzyme engineering opens up an immense variety selective reactions. Biocatalysis especially provides excellent opportunities for late-stage modification often superior to conventional de novo synthesis. Enzymes have proven be useful direct introduction functional groups into complex scaffolds, as well rapid diversification compound libraries. Particularly important highly topical are enzyme-catalysed oxyfunctionalisations, halogenations, methylations, reductions, amide bond formations due high prevalence these motifs pharmaceuticals. This Review gives overview strengths limitations enzymatic modifications using native engineered enzymes synthesis while focusing on examples drug development.

Язык: Английский

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Exploration of the bio-analogous asymmetric C–C coupling mechanism in tandem CO2 electroreduction

Nature Catalysis, Год журнала: 2022, Номер 5(10), С. 878 - 887

Опубликована: Сен. 29, 2022

Язык: Английский

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Modular Dual-Tasked C–H Methylation via the Catellani Strategy

Journal of the American Chemical Society, Год журнала: 2019, Номер 141(40), С. 15986 - 15993

Опубликована: Сен. 12, 2019

We report a dual-tasked methylation that is based on cooperative palladium/norbornene catalysis. Readily available (hetero)aryl halides (39 iodides and 4 bromides) inexpensive MeOTs or trimethylphosphate are utilized as the substrates methylating reagent, respectively. Six types of "ipso" terminations can modularly couple with this "ortho" C–H to constitute versatile toolbox for preparing diversified methylated arenes. This features methyl sources, excellent functional-group tolerance, simple reaction procedures, scalability. Importantly, it be uneventfully extended isotope-labeled by switching corresponding reagents CD3OTs 13CH3OTs. Moreover, applied late-stage modification biorelevant complete stereoretention. believe these salient practical our will welcomed academic industrial researchers.

Язык: Английский

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Mechanochemical Solvent‐Free Catalytic C−H Methylation

Angewandte Chemie International Edition, Год журнала: 2020, Номер 60(12), С. 6660 - 6666

Опубликована: Окт. 8, 2020

The mechanochemical, solvent-free, highly regioselective, rhodium-catalyzed C-H methylation of (hetero)arenes is reported. reaction shows excellent functional-group compatibility and demonstrated to work for the late-stage biologically active compounds. method requires no external heating benefits from considerably shorter times than previous solution-based protocols. Additionally, mechanochemical approach shown enable efficient synthesis organometallic complexes that are difficult generate conventionally.

Язык: Английский

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Iron-Catalyzed Borrowing Hydrogen β-C(sp³)-Methylation of Alcohols

ACS Catalysis, Год журнала: 2019, Номер 9(9), С. 8575 - 8580

Опубликована: Авг. 21, 2019

Herein we report the iron-catalyzed β-C(sp3)-methylation of primary alcohols using methanol as a C1 building block. This borrowing hydrogen approach employs well-defined bench-stable (cyclopentadienone)iron(0) carbonyl complex precatalyst (5 mol %) and enables diverse selection substituted 2-arylethanols to undergo in good isolated yields (24 examples, 65% average yield).

Язык: Английский

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Ruthenium(II) Complexes of Heteroditopic N-Heterocyclic Carbene Ligands: Efficient Catalysts for C–N Bond Formation via a Hydrogen-Borrowing Strategy under Solvent-Free Conditions

Inorganic Chemistry, Год журнала: 2020, Номер 59(3), С. 1835 - 1847

Опубликована: Янв. 13, 2020

Both imidazol-2-ylidene (ImNHC) and 1,2,3-triazol-5-ylidene (tzNHC) have evolved to be elite groups of N-heterocyclic carbene (NHC) ligands for homogeneous catalysis. To develop efficient ruthenium(II)-based catalysts incorporating these C-N bond-forming reactions via hydrogen-borrowing methodology, we utilized chelating integrated with ImNHC mesoionic tzNHC donors connected a CH2 spacer diverse triazole backbone. The synthesized ruthenium(II) complexes 3 are found highly bond formation across wide range primary amine alcohol substrates under solvent-free conditions, among all the studied here, catalyst 3a mesityl substituent displayed maximum activity. our delight, is also effective selective mono-N-methylation various anilines utilizing methanol as coupling partner, known relatively more difficult than other alcohols. Furthermore, complex delivers substituted quinolines successfully reaction 2-aminobenzyl several secondary Importantly, exhibited highest activity reported both N-benzylation aniline [achieving turnover number (TON) 50000] realization quinoline 8a by reacting 2-phenylethanol (attaining TON 30000).

Язык: Английский

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Commercial Pd/C-Catalyzed N-Methylation of Nitroarenes and Amines Using Methanol as Both C1 and H₂ Source

The Journal of Organic Chemistry, Год журнала: 2019, Номер 84(23), С. 15389 - 15398

Опубликована: Ноя. 8, 2019

Herein, we report commercially available carbon-supported-palladium (Pd/C)-catalyzed N-methylation of nitroarenes and amines using MeOH as both a C1 H2 source. This transformation proceeds with high atom-economy in an environmentally friendly way via borrowing hydrogen mechanism. A total >30 structurally diverse N-methylamines, including bioactive compounds, were selectively synthesized isolated yields up to 95%. Furthermore, selective deuteration nimesulide, nonsteroidal anti-inflammatory drug, realized through the late-stage functionalization.

Язык: Английский

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Electrochemical Reductive N-Methylation with CO₂ Enabled by a Molecular Catalyst

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(47), С. 19983 - 19991

Опубликована: Ноя. 16, 2021

The development of benign methylation reactions utilizing CO2 as a one-carbon building block would enable more sustainable chemical industry. Electrochemical reduction has been extensively studied, but its application for reductive remains out the scope current electrocatalysis. Here, we report first electrochemical N-methylation reaction with and demonstrate compatibility amines, hydroxylamines, hydrazine. Catalyzed by cobalt phthalocyanine molecules supported on carbon nanotubes, proceeds in aqueous media via condensation an electrophilic intermediate, proposed to be adsorbed or near-electrode formaldehyde formed from four-electron CO2, nucleophilic nitrogenous reactants subsequent reduction. By comparing various discover that nucleophilicity amine reactant is descriptor C–N coupling efficacy. We extend compatible cheap abundant nitro-compounds developing cascade process which are reduced concurrently yield N-methylamines high monomethylation selectivity overall transfer 12 electrons protons.

Язык: Английский

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