Deoxytrifluoromethylation of Alcohols

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(27), С. 11961 - 11968

Опубликована: Июль 5, 2022

Deoxy-functionalization of alcohols represents a class reactions that has had profound impact on modern medicine. In particular, deoxyfluorination is commonly employed as means to incorporate high-value fluorine atoms into drug-like molecules. Recently, the trifluoromethyl (CF3) group garnered attention from medicinal chemists due its ability markedly improve pharmaceutical properties small-molecule drug candidates. To date, however, there remains no general accomplish analogous deoxygenative trifluoromethylation alcohols. We report herein copper metallaphotoredox-mediated direct deoxytrifluoromethylation, wherein alcohol substrates are activated in situ by benzoxazolium salts for C(sp3)-CF3 bond formation.

Язык: Английский

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Nickel Catalysis via S_H2 Homolytic Substitution: The Double Decarboxylative Cross-Coupling of Aliphatic Acids

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(46), С. 21278 - 21286

Опубликована: Ноя. 14, 2022

Cross-coupling platforms are traditionally built around a sequence of closed-shell steps, such as oxidative addition, transmetalation, and reductive elimination. Herein, we describe dual photo/nickel catalytic manifold that performs cross-coupling via complementary involving free radical generation, sorting selective binding to Ni(II) center, bimolecular homolytic substitution (SH2) at high-valent nickel-alkyl complex. This enables the hitherto elusive diverse aliphatic carboxylic acids generate valuable C(sp3)-C(sp3)-products. Notably, powerful SH2 mechanism provides general access sterically encumbered quaternary carbon centers, addressing long-standing challenge in fragment coupling chemistry.

Язык: Английский

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Late-Stage C(sp³)–H Methylation of Drug Molecules

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(5), С. 2787 - 2793

Опубликована: Янв. 25, 2023

Methyl groups are well understood to play a critical role in pharmaceutical molecules, especially those bearing saturated heterocyclic cores. Accordingly, methods that install methyl onto complex molecules highly coveted. Late-stage C-H functionalization is particularly attractive approach, allowing chemists bypass lengthy syntheses and facilitating the expedited synthesis of drug analogues. Herein, we disclose direct introduction via C(sp3)-H broad array heterocycles, enabled by merger decatungstate photocatalysis unique nickel-mediated SH2 bond formation. To further demonstrate its synthetic utility as tool for late-stage functionalization, this method was applied range en route an methylated

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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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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Polypyridyl Ru(ii) or cyclometalated Ir(iii) functionalized architectures for photocatalysis

Chemical Society Reviews, Год журнала: 2023, Номер 52(14), С. 4725 - 4754

Опубликована: Янв. 1, 2023

The strategies of integrating the well-known photocatalysts Ru(N^N) 3 and Ir(C^N) 2 (X^N) derivatives into cavities well-defined architectures their photocatalytic properties are presented in this review.

Язык: Английский

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Alcohol-alcohol cross-coupling enabled by S _H 2 radical sorting

Science, Год журнала: 2024, Номер 383(6689), С. 1350 - 1357

Опубликована: Март 21, 2024

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target maximizing exploration space, harnessing these building blocks for carbon-carbon bond-forming reactions is key goal in organic chemistry. particular, leveraging single activation mode form new C(sp

Язык: Английский

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Photoinduced, metal- and photosensitizer-free decarboxylative C–H (amino)alkylation of heteroarenes in a sustainable solvent

Green Chemistry, Год журнала: 2023, Номер 25(5), С. 1975 - 1981

Опубликована: Янв. 1, 2023

This study describes a green and sustainable photoinduced strategy for decarboxylative C–H (amino)alkylation of heteroarenes with carboxylic acids under metal- photosensitizer-free conditions.

Язык: Английский

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Alkene dialkylation by triple radical sorting

Nature, Год журнала: 2024, Номер 628(8006), С. 104 - 109

Опубликована: Фев. 13, 2024

Язык: Английский

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