Difluoromethylation of Unactivated Alkenes Using Freon-22 through Tertiary Amine-Borane-Triggered Halogen Atom Transfer

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(31), С. 14288 - 14296

Опубликована: Июль 27, 2022

The application of abundant and inexpensive fluorine feedstock sources to synthesize fluorinated compounds is an appealing yet underexplored strategy. Here, we report a photocatalytic radical hydrodifluoromethylation unactivated alkenes with industrial chemical, chlorodifluoromethane (ClCF2H, Freon-22). This protocol realized by merging tertiary amine-ligated boryl radical-induced halogen atom transfer (XAT) organophotoredox catalysis under blue light irradiation. A broad scope readily accessible featuring variety functional groups drug natural product moieties could be selectively difluoromethylated good efficiency in metal-free manner. Combined experimental computational studies suggest that the key XAT process ClCF2H both thermodynamically kinetically favored over hydrogen pathway owing formation strong boron–chlorine (B–Cl) bond low-lying antibonding orbital carbon–chlorine (C–Cl) bond.

Язык: Английский

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Photoinduced Hydrodifluoromethylation and Hydromethylation of Alkenes Enabled by Ligand-to-Iron Charge Transfer Mediated Decarboxylation

ACS Catalysis, Год журнала: 2024, Номер 14(3), С. 1300 - 1310

Опубликована: Янв. 11, 2024

Directly utilizing abundant and inexpensive sources of aliphatic carboxylic acids is highly attractive for the synthesis CF2H- CH3-containing compounds. Herein, we report a versatile photoinduced iron-catalyzed platform hydrodifluoromethylation hydromethylation alkenes without need additional stoichiometric oxidants. These two transformations are accomplished by visible-light-induced ligand-to-iron charge transfer open-shell activation system using industrial chemical difluoroacetic acetic as precursors postulated to operate via difluoromethyl methyl radical-mediated decarboxylation mechanism. Experimental results show that strategy also applicable difunctionalization unactivated alkenes. Meanwhile, this provides viable route pharmaceutically active molecules containing deuterated units. The protocol exhibits several features, including mild reaction conditions, divergent radical precursors, operational simplicity scalability, good chemo- regioselectivity, scalability supported continuous flow technology, ability provide high-value building blocks applications in one step.

Язык: Английский

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Review and Theoretical Analysis of Fluorinated Radicals in Direct C_Ar−H Functionalization of (Hetero)arenes

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(16)

Опубликована: Янв. 29, 2024

Abstract We highlight key contributions in the field of direct radical C Ar − H (hetero)aromatic functionalization involving fluorinated radicals. A compilation Functional Group Transfer Reagents and their diverse activation mechanisms leading to release radicals are discussed. The substrate scope for each is analyzed classified into three categories according electronic properties substrates. Density functional theory computational analysis provides insights chemical reactivity several through electrophilicity nucleophilicity parameters. Theoretical reduction potentials also highlights remarkable correlation between oxidizing ability. It established that highly (e.g. ⋅OCF 3 ) capable engaging single‐electron transfer (SET) processes rather than addition, which good agreement with experimental literature data. scale, based on barrier addition these benzene elaborated using high accuracy DLPNO‐(U)CCSD(T) method.

Язык: Английский

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Hydroalkylation of Unactivated Olefins via Visible-Light-Driven Dual Hydrogen Atom Transfer Catalysis

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(29), С. 11251 - 11261

Опубликована: Июль 16, 2021

Radical hydroalkylation of olefins enabled by hydrogen atom transfer (HAT) catalysis represents a straightforward means to access C(sp3)-rich molecules from abundant feedstock chemicals without the need for prefunctionalization. While Giese-type activated initiated HAT hydridic carbon-hydrogen bonds is well-precedented, unactivated in similar fashion remains elusive, primarily owing lack general methods overcome inherent polarity-mismatch this scenario. Here, we report use visible-light-driven dual achieve goal, where catalytic amounts an amine-borane and situ generated thiol were utilized as abstractor donor, respectively. The reaction completely atom-economical exhibits broad scope. Experimental computational studies support proposed mechanism suggest that hydrogen-bonding between substrates beneficial improving efficiency.

Язык: Английский

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Photoinduced manganese-catalysed hydrofluorocarbofunctionalization of alkenes

Nature Synthesis, Год журнала: 2022, Номер 1(6), С. 475 - 486

Опубликована: Май 30, 2022

Язык: Английский

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Site-Divergent Alkenyl C–H Fluoroallylation of Olefins Enabled by Tunable Rhodium Catalysis

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 8857 - 8867

Опубликована: Июль 10, 2022

The unique properties of the fluorine-containing compounds and their widespread applications raise demand for dependable synthetic methods on precise introduction substituents into organic molecules. Herein, a site-divergent fluoroallylation olefins that can incorporate fluoroallyl motif different alkenyl C–H sites is disclosed. gem-Difluorinated cyclopropanes are employed as sources via rhodium-catalyzed C–C bond activation. This strategy provide two regioisomeric fluorinated skipped dienes in good yields with excellent site-selectivity. resulting products serve useful building blocks to access various molecules isosteric β, γ-unsaturated amides, which promising be exploited medicinal chemistry. Mechanistic studies revealed electronic property rhodium catalysts crucial controllable site-selectivity, providing more insights beyond methodology tuning selectivity metal catalysts.

Язык: Английский

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Electrophotocatalytic tri- or difluoromethylative cyclization of alkenes

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(10), С. 2482 - 2490

Опубликована: Янв. 1, 2023

Photoelectrocatalysis is mild yet potent and this work unlocks the potential of unactivated alkenes for oxidant-free oxidative cyclization alkenes.

Язык: Английский

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An in-situ Generated Proton Initiated Aromatic Fluoroalkylation via Electron Donor-Acceptor Complexes Photoactivation

Green Chemistry, Год журнала: 2024, Номер 26(12), С. 7198 - 7205

Опубликована: Янв. 1, 2024

In situ -generated protonated aromatic hydrocarbons overcome their intrinsic electronic properties to serve as catalytic electron acceptors, avoiding the use of photocatalysts, metals, and redox reagents achieve fluoroalkylation.

Язык: Английский

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Selective Fluoromethyl Couplings of Alkynes via Nickel Catalysis

Angewandte Chemie International Edition, Год журнала: 2021, Номер 61(9)

Опубликована: Дек. 28, 2021

We describe here a Ni-catalyzed intermolecular carbo-fluoromethylation of alkynes with aliphatic halides and fluoromethyl (BrCF2 H ICH2 F) in the presence zinc, enabling facile selective access to diverse range biologically valuable CF2 H/CH2 F-incorporated alkenes excellent regio- stereoselectivity. Notably, merging intramolecular radical cyclization coupling enables expedient constructions lactones lactams high efficiency selectivity. Mechanistic studies disclose that this catalytic protocol proceeds via addition an alkyne followed by unit.

Язык: Английский

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Acyldifluoromethylation Enabled by NHC-Photoredox Cocatalysis

Organic Letters, Год журнала: 2022, Номер 24(20), С. 3721 - 3725

Опубликована: Май 12, 2022

With the continued interest in properties of difluoromethyl (CF2H) group, small molecules with alkyl-CF2H motifs have gained increasing attention. However, concise and efficient synthetic protocols to achieve these structures are still urgently needed. Herein, we report a new acyldifluoromethylation inert alkenes via synergistic NHC-photoredox catalysis featuring broad substrate scope good functional group tolerance.

Язык: Английский

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