Sustainable Thioetherification via Electron Donor–Acceptor Photoactivation Using Thianthrenium Salts

Angewandte Chemie International Edition, Год журнала: 2022, Номер 61(22)

Опубликована: Март 16, 2022

Abstract The synthesis of sulfides has been widely studied because this functional subunit is prevalent in biomolecules and pharmaceuticals, as well being a useful synthetic platform for further elaboration. Thus, various methods to build C−S bonds have developed, but typically they require the use precious metals or harsh conditions. Electron donor–acceptor (EDA) complex photoactivation strategies emerged versatile sustainable ways achieve bond formation, avoiding challenges associated with previous methods. This work describes an open‐to‐air, photoinduced, site‐selective C−H thioetherification from readily available reagents via EDA formation that tolerates wide range different groups. Moreover, C(sp 2 )−halogen remain intact using protocol, allowing late‐stage installation sulfide motif bioactive scaffolds, while yet modification through more traditional C−X cleavage protocols. Additionally, mechanistic investigations support envisioned scenario.

Язык: Английский

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Tetrachlorophthalimides as Organocatalytic Acceptors for Electron Donor–Acceptor Complex Photoactivation

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(20), С. 8914 - 8919

Опубликована: Май 13, 2022

Excitation of photoactive electron donor-acceptor (EDA) complexes is an effective way to generate radicals. Applications in a catalytic regime typically use donors. Herein, we report that readily available electron-poor tetrachlorophthalimides can act as organocatalytic acceptors trigger the formation EDA with variety radical precursors not amenable previous methods. visible light generates carbon radicals under mild conditions. The versatility this complex platform allowed us develop mechanistically distinct reactions, including combination cobalt-based system. Quantum yield measurements established closed cycle operational, which hints at ability turn over and govern each cycle.

Язык: Английский

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Reductive quenching-initiated catalyst-controlled divergent alkylation of α-CF3-olefins

Chem Catalysis, Год журнала: 2022, Номер 2(6), С. 1380 - 1393

Опубликована: Апрель 21, 2022

Gem-difluoroalkenes and trifluoromethyl alkanes are pervasive in biologically active molecules. Photo-catalyzed alkylation of α-CF3-olefins provides a straightforward approach to access these scaffolds; however, such strategy is often hampered, gem-difluoroalkenes usually formed instead under reductive quenching-initiated photoredox conditions. It both mechanistically synthetically appealing if simple change the catalyst can chemo-selectively lead either type products. Here, we show visible-light-induced photo-catalyst for preparing from α-CF3-olefins. The chemo-selectivity reactions arises judicious choice rather than modification substrate structures. A wide variety substrates bearing an assortment functional groups (62 examples) compatible with this strategy. use HFIP as additive promotes formation probably via facilitation hydrogen atom transfer step O-H but not α-C-H bond.

Язык: Английский

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Exploiting photoredox catalysis for carbohydrate modification through C–H and C–C bond activation

Nature Reviews Chemistry, Год журнала: 2022, Номер 6(11), С. 782 - 805

Опубликована: Сен. 21, 2022

Язык: Английский

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Light-Driven Cobalt Hydride Catalyzed Hydroarylation of Styrenes

ACS Catalysis, Год журнала: 2022, Номер 12(24), С. 14806 - 14811

Опубликована: Ноя. 22, 2022

We report a conceptually distinct strategy for the synthesis of 1,1-diarylalkanes and triarylalkanes. Key to this approach is use light simultaneously trigger (i) formation CoIII–H species which undergoes H atom transfer (MHAT) styrenes, giving carbon-centered radical, (ii) generation persistent (hetero)arene radical. Selective coupling these two yields Markovnikov hydroarylation products under mild conditions without precious metals. In contrast many previous approaches, electron-deficient partners are favored it possible construct highly congested quaternary centers, including those with three different aryl groups.

Язык: Английский

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Nickel-Catalyzed anti-Markovnikov Hydroalkylation of Trifluoromethylalkenes

ACS Catalysis, Год журнала: 2022, Номер 12(15), С. 9410 - 9417

Опубликована: Июль 18, 2022

Transition-metal-catalyzed difunctionalization of olefins constitutes a fertile synthetic platform for rapid access to complex molecules from bulk chemicals. However, substrates featuring fluoroalkyl substituents are rarely employed because facile β-fluoride elimination pathways. Herein, we report hydroalkylation trifluoromethylalkenes with alkyl halides under nickel catalysis that enables the construction 1,1,1-trifluoropropane derivatives. The common pathway is suppressed by identifying competent proton donor favors protonolysis process. Also, unactivated alkenes could be readily as when using Ni/hydrosilane catalytic system.

Язык: Английский

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On-DNA Hydroalkylation to Introduce Diverse Bicyclo[1.1.1]pentanes and Abundant Alkyls via Halogen Atom Transfer

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(27), С. 12184 - 12191

Опубликована: Июнь 27, 2022

DNA-encoded libraries have proven their tremendous value in the identification of new lead compounds for drug discovery. To access chemical space, many methods emerged to transpose traditional mol-scale reactivity nmol-scale, on-DNA chemistry. However, procedures with a greater fraction C(sp3) content are still limited, and need "escape from flatland" more readily remains. Herein, we report Giese addition install highly functionalized bicyclo[1.1.1]pentanes (BCPs) using tricyclo[1.1.1.01,3]pentane (TCP) as radical linchpin, well other diverse alkyl groups, corresponding organohalides non-stabilized precursors. Telescoped allow extension substrate pool by at least an order magnitude ubiquitous alcohols carboxylic acids, allowing us "upcycle" these abundant feedstocks afford non-traditional different physicochemical properties small-molecule products (i.e., non-peptide acids). This approach is amenable library production, DNA damage assessment revealed good PCR amplifiability only 6% mutated sequences full-length tag.

Язык: Английский

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Photochemical Methods Applied to DNA Encoded Library (DEL) Synthesis

Accounts of Chemical Research, Год журнала: 2023, Номер 56(3), С. 385 - 401

Опубликована: Янв. 19, 2023

ConspectusDNA-encoded library technology (DELT) is a new screening modality that allows efficient, cost-effective, and rapid identification of small molecules with potential biological activity. This emerging technique represents an enormous advancement that, in combination other technologies such as high-throughput (HTS), fragment-based lead generation, structure-based drug design, has the to transform how discovery carried out. DELT hybrid which chemically synthesized compounds are linked unique genetic tags (or "barcodes") contain readable information. In this way, millions billions building blocks (BBs) attached on-DNA via split-and-pool synthesis can be evaluated against target single experiment. Polymerase chain reaction (PCR) amplification next-generation sequencing (NGS) analysis sequence oligonucleotides DNA tag used identify those ligands high affinity for target. innovative fusion chemical was conceived 1992 by Brenner Lerner (Proc. Natl. Acad. Sci. 1992, 89, 5381–5383) under accelerated development implementation synthetic techniques protocols compatible DNA. fact, compatibility key parameter increasing chances ligand, central focus been transformations transition robust synthesis. Because sole use amplifiable barcode, its structural integrity during process mandatory. As such, these sensitive, polyfunctional substrates typically requires aqueous solutions within defined pH temperature ranges, considered notable challenge DEL synthesis.Using low-energy visible light driving force promote attractive alternative classical methods, it important well-established tool forging bonds way radical intermediates. Recent advances field photocatalysis extraordinary, powerful research arena still continuous development. Several applications taking advantage mild conditions photoinduced have directed toward synthesis, allowing expansion space available evaluation on-DNA. There no doubts visible-light-driven reactions become one most approaches DELT, given easy they provide construct challenges achieve equal success protocols.Key characteristics photocatalytic include short times efficiency, translate into retention integrity. Account, we describe recent diversification prepared on-DNA, highlighting amenability employed preserving structure molecules. We demonstrate from our group applicability summary table containing all methods reported date demonstrating their aspects scope, applications, compatibilities. With information, practitioners provided compelling reasons developing/choosing applications.

Язык: Английский

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Evolution of chemistry and selection technology for DNA-encoded library

Acta Pharmaceutica Sinica B, Год журнала: 2023, Номер 14(2), С. 492 - 516

Опубликована: Окт. 11, 2023

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and non-self-replicating phenotypes, generating a diverse world. In analogy with biological world, DEL world can evolve by using central dogma, wherein DNA replicates PCR reactions to amplify genetic codes, sequencing transcripts information, DNA-compatible synthesis translates into phenotypes. Importantly, is key expanding space. Besides, evolution-driven selection system pushes chemicals under selective pressure, i.e., desired strategies. this perspective, we summarized recent advances in synthetic toolbox panning strategies, which will shed light on drug discovery harnessing vitro evolution via DEL.

Язык: Английский

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Photoinduced Triphenylphosphine and Iodide Salt Promoted Reductive Decarboxylative Coupling

Advanced Science, Год журнала: 2024, Номер 11(12)

Опубликована: Янв. 17, 2024

Abstract The transient electron donor–acceptor (EDA) complex has been an emerging area in the photoinduced organic synthesis field, generating radicals without exogenous transition‐metal or dye‐based photoredox catalysts. catalytic platform to form suitable photoactive EDA complexes for photochemical reduction reactions remains underdeveloped. Herein, a general reductive alkylation via strategy is described. A simple yet multifunctional system, triphenylphosphine and iodide salt, promotes decarboxylative hydroalkylation, defluorinative of trifluoromethyl alkenes, access alkanes gem ‐difluoroalkenes. Moreover, hydroalkylation can be applied more kinds electron‐deficient alkenes as Giese addition reaction.

Язык: Английский

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