Recent advances in transition metal-mediated trifluoromethylation reactions

Chemical Communications, Год журнала: 2022, Номер 58(75), С. 10442 - 10468

Опубликована: Янв. 1, 2022

Fluorine compounds are known for their abundance in more than 20% of pharmaceutical and agrochemical products mainly due to the enhanced lipophilicity, metabolic stability pharmacokinetic properties organofluorides. Consequently, last decade has seen enormous growth incorporation a trifluoromethyl group into organic motifs. With significance, this review aims provide complete picture transition metal-mediated construction C(sp3, sp2, sp)-CF3 bonds via C-H/X bond functionalization or addition processes both aliphatic aromatic hydrocarbons. Diversified reagents ranging from radical electrophilic nucleophilic trifluoromethylating agents respective mechanisms have been further deliberated comprehensive overview. The coverage on topic is expected make unique beneficial future applications enriching community towards improvements field trifluoromethylation reactions, turn improving propensity development drugs.

Язык: Английский

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Expedient Access to Underexplored Chemical Space: Deoxygenative C(sp³)–C(sp³) Cross-Coupling

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(14), С. 7736 - 7742

Опубликована: Март 28, 2023

Alcohols are commercially abundant and structurally diverse reservoirs of sp3-hybridized chemical space. However, the direct utilization alcohols in C-C bond-forming cross-couplings remains underexplored. Herein we report an N-heterocyclic carbene (NHC)-mediated deoxygenative alkylation alkyl bromides via nickel-metallaphotoredox catalysis. This C(sp3)-C(sp3) cross-coupling exhibits a broad scope is capable forming bonds between two secondary carbon centers, longstanding challenge field. Highly strained three-dimensional systems such as spirocycles, bicycles, fused rings were excellent substrates, enabling synthesis new molecular frameworks. Linkages pharmacophoric saturated ring readily forged, representing alternative to traditional biaryl formation. The utility this technology highlighted with expedited bioactive molecules.

Язык: Английский

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Highlights on U.S. FDA-approved fluorinated drugs over the past five years (2018–2022)

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 256, С. 115476 - 115476

Опубликована: Май 15, 2023

Язык: Английский

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Reductive Deoxygenative Functionalization of Alcohols by First‐Row Transition Metal Catalysis

Chinese Journal of Chemistry, Год журнала: 2023, Номер 41(13), С. 1637 - 1652

Опубликована: Янв. 23, 2023

Comprehensive Summary Alcohols are among the most accessible functionalities. Catalytic deoxygenative functionalization of alcohols is highly synthetically appealing. While significant progress has been made on reactions with nucleophiles, electrophilic coupling partners remain a real challenge. This manuscript highlights advance in this direction, which mainly achieved by first‐row transition metals. The low‐valent titanium catalyst shown unique reactivity to homolytically cleave C—OH bonds. formed carbon radicals could either undergo reduction give protonation products or couple fragments form C—C chemistry initially realized using stoichiometric amount reagents and later extended catalytic variants. Nickel features variety oxidation states ranging from Ni 0 IV , both two‐electron oxidative addition single‐electron process involved their activation an electrophile. These properties enable nickel catalyze reductive R–X electrophiles. reaction first reported allylic alcohols, then benzylic and, very recently non‐activated alcohols. Recent effort resulted many invaluable methodologies that improve efficiency for construction aliphatic use cobalt copper catalysts not only expands substrate scope these but also shows new selectivity issues.

Язык: Английский

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Rapid and Modular Access to Quaternary Carbons from Tertiary Alcohols via Bimolecular Homolytic Substitution

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16330 - 16336

Опубликована: Июль 20, 2023

Quaternary carbons are ubiquitous in bioactive molecules; however, synthetic methods for the construction of this motif remain underdeveloped. Here, we report synthesis quaternary from tertiary alcohols, a class structurally diverse, bench-stable feedstocks, via merger photoredox catalysis and iron-mediated SH2 bond formation. This alcohol-bromide cross-coupling is enabled by novel halogen-atom transfer (XAT) reagent, which first reductively activated XAT reagent to be reported. A wide variety sterically congested products can accessed through mild practical protocol including derived both alkylation benzylation fragments. We further demonstrate utility method expedited liver receptor agonist two-step conversion ketones esters products, enables modular control up three four substituents on center.

Язык: Английский

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Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions

Chemical Reviews, Год журнала: 2024, Номер 124(9), С. 6078 - 6144

Опубликована: Апрель 17, 2024

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods their functionalization require them to first be converted into a more activated derivative, while recent years have seen vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can used toward this goal. These broadly classified three categories. Deoxygenative functionalizations, representing derivatization C–O bond, enable alcohol act as leaving group formation new C–C bonds. Etherifications, characterized by O–H represent classical reactivity has been modernized include mild reaction conditions, diverse partners, high selectivities. Lastly, chain reactions described, wherein acts mediator formal C–H alkyl backbone. Each these classes transformation will discussed context intermolecular arylation, alkylation, related reactions, illustrating alcohols harnessed

Язык: Английский

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Development of a General Organophosphorus Radical Trap: Deoxyphosphonylation of Alcohols

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(12), С. 7942 - 7949

Опубликована: Март 12, 2024

Here we report the design of a general, redox-switchable organophosphorus alkyl radical trap that enables synthesis broad range C(sp3)–P(V) modalities. This "plug-and-play" approach relies upon in situ activation alcohols and O═P(R2)H motifs, two broadly available inexpensive sources molecular complexity. The mild, photocatalytic deoxygenative strategy described herein allows for direct conversion sugars, nucleosides, complex pharmaceutical architectures to their analogs. includes facile incorporation medicinally relevant phosphonate ester prodrugs.

Язык: Английский

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Direct Bioisostere Replacement Enabled by Metallaphotoredox Deoxydifluoromethylation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(8), С. 5067 - 5073

Опубликована: Фев. 16, 2024

The replacement of a functional group with its corresponding bioisostere is widely employed tactic during drug discovery campaigns that allows medicinal chemists to improve the ADME properties candidates while maintaining potency. However, incorporation bioisosteres typically requires lengthy de novo resynthesis potential candidates, which represents bottleneck in their broader evaluation. An alternative would be directly convert into at late stage. Herein, we report realization this approach through conversion aliphatic alcohols difluoromethylated analogues via merger benzoxazolium-mediated deoxygenation and copper-mediated C(sp3)–CF2H bond formation. utility method showcased variety complex compounds.

Язык: Английский

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Engaging Alkenes in Metallaphotoredox: A Triple Catalytic, Radical Sorting Approach to Olefin-Alcohol Cross-Coupling

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(18), С. 12300 - 12309

Опубликована: Апрель 24, 2024

Metallaphotoredox cross-coupling is a well-established strategy for generating clinically privileged aliphatic scaffolds via single-electron reactivity. Correspondingly, expanding metallaphotoredox to encompass new C(

Язык: Английский

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Harnessing alcohols as sustainable reagents for late-stage functionalisation: synthesis of drugs and bio-inspired compounds

Chemical Society Reviews, Год журнала: 2024, Номер 53(9), С. 4607 - 4647

Опубликована: Янв. 1, 2024

This review collectively discussed the utilisation of alcohols in various organic transformations and their application toward intermediates drugs, drug derivatives natural product-like molecules.

Язык: Английский

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