A Visible‐Light‐Mediated Radical Smiles Rearrangement and its Application to the Synthesis of a Difluoro‐Substituted Spirocyclic ORL‐1 Antagonist

Angewandte Chemie International Edition, Год журнала: 2015, Номер 54(49), С. 14898 - 14902

Опубликована: Окт. 16, 2015

Abstract A visible‐light‐mediated radical Smiles rearrangement has been developed to address the challenging synthesis of gem ‐difluoro group present in an opioid receptor‐like 1 (ORL‐1) antagonist that is currently development for treatment depression and/or obesity. This method enables direct and efficient introduction difluoroethanol motif into a range aryl heteroaryl systems, representing new disconnection this versatile moiety. When applied target compound, photochemical step could be conducted on 15 g scale using industrially relevant [Ru(bpy) 3 Cl 2 ] catalyst loadings 0.01 mol %. transformation part overall five‐step route compares favorably current synthetic sequence demonstrates, specific case, clear strategic benefit photocatalysis.

Язык: Английский

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China's flourishing synthetic organofluorine chemistry: innovations in the new millennium

National Science Review, Год журнала: 2017, Номер 4(3), С. 303 - 325

Опубликована: Май 1, 2017

Abstract The new millennium has witnessed the rapid development of synthetic organofluorine chemistry all over world, and chemists in China have made significant contributions this field. This review aims to provide a brief introduction China's primary innovations from 2000 early 2017, covering fluorination, fluoroalkylation, fluoromethylthiolation, fluoroolefination polyfluoroarylation, as well synthesis with fluorinated building blocks. Recent advances difluorocarbene carbon–fluorine bond activation are also discussed. As conclusion, ends some personal perspectives on future chemistry.

Язык: Английский

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Enantioselective Copper-Catalyzed Defluoroalkylation Using Arylboronate-Activated Alkyl Grignard Reagents

Journal of the American Chemical Society, Год журнала: 2018, Номер 140(29), С. 9061 - 9065

Опубликована: Июль 10, 2018

A copper-catalyzed system has been introduced for the enantioselective defluoroalkylation of linear 1-(trifluoromethyl)alkenes through C-F activation to synthesize various gem-difluoroalkenes as carbonyl mimics. For first time, arylboronate-activated alkyl Grignard reagents were uncovered in this cross-coupling reaction. Mechanistic studies confirmed that tetraorganoborate complexes generated situ key reactive species transformation.

Язык: Английский

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Efficient Docking–Migration Strategy for Selective Radical Difluoromethylation of Alkenes

Angewandte Chemie International Edition, Год журнала: 2018, Номер 57(52), С. 17156 - 17160

Опубликована: Ноя. 6, 2018

Abstract Radical‐mediated difunctionalization of alkenes is a powerful tactic for olefin utilization. However, the transformation unactivated still remains formidable challenge. Now conceptually new docking–migration strategy presented with photoredox catalysis. Both activated and are suitable substrates. A vast array functional groups compatible mild reaction conditions. Heteroaryl difluoromethyl concomitantly incorporated into alkenes, leading to synthetically valuable products that readily converted variety fluorine‐containing molecules. The protocol provides kinetic control stereoselectivity cycloalkenes generate unusual cis‐products, offers an efficient approach late‐stage functionalization complex natural drug portfolio dual‐function reagents prepared elusive radical alkenes.

Язык: Английский

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Heck Reaction of Electronically Diverse Tertiary Alkyl Halides

Organic Letters, Год журнала: 2018, Номер 20(2), С. 357 - 360

Опубликована: Янв. 5, 2018

The efficient Pd-catalyzed Heck reaction of diverse tertiary alkyl halides with alkenes has been developed. Unactivated efficiently react at room temperature under visible light irradiation no exogenous photosensitizers required. For activated halides, the same catalytic system works well without light. These methods offer a general access to electronically possessing quaternary and functionalized allylic carbon centers. substituents these centers include alkyl-, carbalkoxy-, tosyl-, phosphonyl-, boronate groups. It was also shown that end-game mechanism this transformation may vary depending on type substrates used.

Язык: Английский

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Nickel‐Catalyzed Decarboxylative Difluoroalkylation of α,β‐Unsaturated Carboxylic Acids

Angewandte Chemie International Edition, Год журнала: 2016, Номер 55(10), С. 3491 - 3495

Опубликована: Фев. 2, 2016

Abstract The first example of nickel‐catalyzed decarboxylative fluoroalkylation α,β‐unsaturated carboxylic acids has been developed with commonly available fluoroalkyl halides. This novel transformation demonstrated broad substrate scope, excellent functional‐group tolerance, mild reaction conditions, and stereoselectivity. Mechanistic investigations indicate that a radical is involved in the catalytic cycle.

Язык: Английский

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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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Atom Transfer Radical Addition to Alkynes and Enynes: A Versatile Gold/Photoredox Approach to Thio-Functionalized Vinylsulfones

ACS Catalysis, Год журнала: 2018, Номер 8(9), С. 8237 - 8243

Опубликована: Июль 25, 2018

An efficient intermolecular atom-transfer addition reaction of alkynes via the combination visible-light photoredox catalysis and gold has been developed, affording diverse trifluoromethylthio- difluoromethylthio-functionalized vinylsulfones with high stereoselectivity in good yields. Thiosulfonylation enyne can also be realized for constructing functionalized carbo- heterocycles through a radical cascade cyclization process. These reactions proceed gold-assisted sulfonyl pathway.

Язык: Английский

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Copper-Catalyzed C–H Difluoroalkylations and Perfluoroalkylations of Alkenes and (Hetero)arenes

Organic Letters, Год журнала: 2017, Номер 19(16), С. 4187 - 4190

Опубликована: Авг. 7, 2017

A general and facile synthetic method for C(sp2)–H difluoroalkylations perfluoroalkylations of alkenes (hetero)arenes with commercially available fluoroalkyl halides has been developed a copper-amine catalyst system. This is characterized by high yields, mild reaction conditions, low-cost catalyst, broad substrate scope, excellent functional group compatibility, therefore providing convenient strategy toward various difluoroalkyl- perfluoroalkyl-substituted (hetero)arenes.

Язык: Английский

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Radical Dehydroxylative Alkylation of Tertiary Alcohols by Ti Catalysis

Journal of the American Chemical Society, Год журнала: 2020, Номер 142(39), С. 16787 - 16794

Опубликована: Сен. 4, 2020

Deoxygenative radical C–C bond-forming reactions of alcohols are a long-standing challenge in synthetic chemistry, and the current methods rely on multistep procedures. Herein, we report direct dehydroxylative alkylation reaction tertiary alcohols. This new protocol shows feasibility generating carbon radicals from offers an approach for facile precise construction all-carbon quaternary centers. The proceeds with broad substrate scope activated alkenes. It can tolerate wide range electrophilic coupling partners, including allylic carboxylates, aryl vinyl electrophiles, primary alkyl chlorides/bromides, making method complementary to cross-coupling is highly selective alcohols, leaving secondary/primary (benzyl included) phenols intact. utility highlighted by its 10-g-scale late-stage modification complex molecules. A combination experiments density functional theory calculations establishes plausible mechanism implicating generated via Ti-catalyzed homolysis C–OH bond.

Язык: Английский

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