Direct Decarboxylation of Trifluoroacetates Enabled by Iron Photocatalysis**

Angewandte Chemie International Edition, Год журнала: 2023, Номер 63(5)

Опубликована: Дек. 13, 2023

Trifluoroacetates are the most abundant and accessible sources of trifluoromethyl groups, which key components in pharmaceuticals agrochemicals. The generation reactive radicals from trifluoroacetates requires their decarboxylation, is hampered by high oxidation potential. This constitutes a major challenge for redox-based methods, because need to pair redox potentials with trifluoroacetate. Here we report strategy based on iron photocatalysis promote direct photodecarboxylation that displays reactivity features escape limitations. Our synthetic design has enabled use trifluoromethylation more easily oxidizable organic substrates, offering new opportunities late-stage derivatization campaigns using chemical feedstocks, Earth-abundant catalysts, visible-light.

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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Recent Advances in Electron Donor‐Acceptor (EDA)‐Complex Reactions involving Quaternary Pyridinium Derivatives

Advanced Synthesis & Catalysis, Год журнала: 2023, Номер 365(10), С. 1538 - 1564

Опубликована: Март 6, 2023

Abstract Quaternary pyridinium compounds are valuable intermediates in organic synthesis, which have gained immense popularity the synthetic community. The application of transition metal or photoredox catalysis transforming quaternary into various C−C and C−X bonds is well established. A majority these methods require high temperatures, expansive catalysts, delicate conditions for successful execution. On other hand, use metal‐free photocatalysis‐free strategies constructing using derivatives has been sought‐after. In this context, electron‐donor‐acceptor (EDA)‐complex reactions emerged as a state‐of‐the‐art methodology, do not any photocatalyst their EDA‐complex photochemistry takes advantage electron‐acceptor ability derivatives, can quickly generate radical precursor via deaminative process. These newly generated useful several transformations. We hereby, review, discuss an area major progress mediated involving with mechanism, substrate scope, limitations. magnified image

Язык: Английский

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The Rational Design of Reducing Organophotoredox Catalysts Unlocks Proton-Coupled Electron-Transfer and Atom Transfer Radical Polymerization Mechanisms

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(3), С. 1835 - 1846

Опубликована: Янв. 6, 2023

Photocatalysis has become a prominent tool in the arsenal of organic chemists to develop and (re)imagine transformations. However, only handful versatile photocatalysts (PCs) are available, hampering discovery new reactivities. Here, we report design complete physicochemical characterization 9-aryl dihydroacridines (9ADA) 12-aryl dihydrobenzoacridines (12ADBA) as strong reducing PCs. Punctual structural variations modulate their molecular orbital distributions unlock locally or charge-transfer (CT) excited states. The PCs presenting state showed better performances photoredox defunctionalization processes (yields up 92%), whereas featuring CT produced promising results atom transfer radical polymerization under visible light (up 1.21 Đ, 98% I*). Unlike all PC classes reported so far, 9ADA 12ADBA feature free NH group that enables catalytic multisite proton-coupled electron (MS-PCET) mechanism. This manifold allows reduction redox-inert substrates including aryl, alkyl halides, azides, phosphate ammonium salts (Ered -2.83 vs SCE) single-photon excitation. We anticipate these will open mechanistic manifolds field photocatalysis by allowing access previously inaccessible intermediates one-photon

Язык: Английский

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General and Modular Route to (Halo)alkyl BCP-Heteroaryls Enabled by α-Aminoalkyl Radical-Mediated Halogen-Atom Transfer

ACS Catalysis, Год журнала: 2023, Номер 14(2), С. 619 - 627

Опубликована: Дек. 28, 2023

Synthesis of bicyclo[1.1.1]pentane (BCP) heteroaryls continues to be a part the most important tasks in organic synthesis because they are significant class bioisosteres with universal applications drug discovery. However, substrate scope current multicomponent reactions is limited tertiary alkyl radicals and prefunctionalized (het)arenes due their intrinsic mechanisms, resulting decrease application value. Herein, we report straightforward alternative for (halo)alkyl BCP-heteroaryls from [1.1.1]propellane enabled by α-aminoalkyl radical-mediated halogen-atom transfer (XAT). Carbon derived commonly available precursors such as primary, secondary, halides polyhalides perform additions onto give BCP radicals, which then engage C–H/C–C couplings different heteroarenes. A wide range easily constructed moderate-to-good yields. Late-stage functionalization performed on approved derivatives proceeds good efficiency produce corresponding BCP-heteroaryls. The control experiments density functional theory (DFT) calculations reveal radical nature reaction. This approach not only verifies (XAT) strategy but also provides practical efficient route multifunctionalized BCPs, significantly expands BCP-heteroaryl-type development.

Язык: Английский

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Synthesis of 1-(Halo)alkyl-3-heteroaryl Bicyclo[1.1.1]pentanes Enabled by a Photocatalytic Minisci-type Multicomponent Reaction

ACS Catalysis, Год журнала: 2024, Номер 14(8), С. 6247 - 6258

Опубликована: Апрель 10, 2024

Aryl-substituted bicyclo[1.1.1]pentane (BCP-aryl) derivatives represent the most important bioisosteres of biaryl scaffolds and widely exist in numerous complex pharmaceutical molecules. The current synthetic method limitations using only tertiary radical precursors, prefunctionalized heteroarenes, toxic transition metals, expensive photocatalysts make it urgent to develop a more simple practical protocol. To confront enrich Minisci-type chemistry, herein, we disclose photocatalytic multicomponent reaction for synthesis various (halo)alkyl BCP-aryls [1.1.1]propellane, alkyl halides, unfunctionalized heteroarenes as starting materials. Diverse kinds radicals (primary, secondary, carbons) derived from chlorides, bromides, fluoroalkyl iodides are very compatible this transformation. practicability is additionally boosted by product derivatizations late-stage functionalization pharmaceutically relevant mechanistic studies demonstrate that relay mechanism initiated consecutive photoinduced electron transfer (ConPET) process operation. We anticipate methodology would act useful tool biaryl-type drug derivatives, ultimately resulting great utility discovery program.

Язык: Английский

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Recent advances in FeCl3-photocatalyzed organic reactions via hydrogen-atom transfer

Chinese Chemical Letters, Год журнала: 2024, Номер 35(9), С. 109517 - 109517

Опубликована: Янв. 21, 2024

Язык: Английский

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A Bimolecular Homolytic Substitution-Enabled Platform for Multicomponent Cross-Coupling of Unactivated Alkenes

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(15), С. 10274 - 10280

Опубликована: Апрель 3, 2024

The construction of C(sp3)–C(sp3) bonds remains one the most difficult challenges in cross-coupling chemistry. Here, we report a photoredox/nickel dual catalytic approach that enables simultaneous formation two linkages via trimolecular alkenes with alkyl halides and hypervalent iodine-based reagents. reaction harnesses bimolecular homolytic substitution (SH2) mechanism chemoselective halogen-atom transfer (XAT) to orchestrate regioselective addition electrophilic nucleophilic radicals across unactivated without need for directing auxiliary. Utility is highlighted through late-stage (fluoro)alkylation (trideutero)methylation C═C bearing different patterns, offering straightforward access drug-like molecules comprising sp3-hybridized carbon scaffolds.

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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Challenges and Future Perspectives in Photocatalysis: Conclusions from an Interdisciplinary Workshop

JACS Au, Год журнала: 2024, Номер 4(8), С. 2746 - 2766

Опубликована: Авг. 8, 2024

Photocatalysis is a versatile and rapidly developing field with applications spanning artificial photosynthesis, photo-biocatalysis, photoredox catalysis in solution or supramolecular structures, utilization of abundant metals organocatalysts, sustainable synthesis, plastic degradation. In this Perspective, we summarize conclusions from an interdisciplinary workshop young principal investigators held at the Lorentz Center Leiden March 2023. We explore how diverse fields within photocatalysis can benefit one another. delve into intricate interplay between these subdisciplines, by highlighting unique challenges opportunities presented each multidisciplinary approach drive innovation lead to solutions for future. Advanced collaboration knowledge exchange across domains further enhance potential photocatalysis. Artificial photosynthesis has become promising technology solar fuel generation, instance, via water splitting CO

Язык: Английский

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