Palladium (II)‐Catalyzed C−H Activation with Bifunctional Ligands: From Curiosity to Industrialization

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(19)

Опубликована: Фев. 29, 2024

Abstract In 2001, our curiosity to understand the stereochemistry of C−H metalation with Pd prompted first studies in Pd(II)‐catalyzed asymmetric activation (RSC Research appointment: 020 7451 2545, Grant: RG 36873, Dec. 2002). We identified four central challenges: 1. poor reactivity simple salts native substrates; 2. few strategies control site selectivity for remote bonds; 3. lack chiral catalysts achieve enantioselectivity via metalation, and 4. low practicality due limited coupling partner scope use specialized oxidants. These challenges necessitated new catalyst reaction development. For , we developed approaches enhance substrate–catalyst affinity together novel bifunctional ligands which participate accelerate cleavage step. site‐selectivity introduced concept systematically modulating distance geometry between a directing template, catalyst, substrate selectively access bonds. devised predictable stereomodels catalyst‐controlled enantioselective based on participation ligands. Finally, have varied catalytic manifolds Pd(II) accommodate diverse partners while employing practical oxidants such as peroxides. advances culminated numerous reactions, setting stage broad industrial applications.

Язык: Английский

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Biopesticide Compounds from an Endolichenic Fungus Xylaria sp. Isolated from the Lichen Hypogymnia tubulosa

Molecules, Год журнала: 2025, Номер 30(3), С. 470 - 470

Опубликована: Янв. 22, 2025

Endolichenic fungi represent an important ecological group of microorganisms that form associations with photobionts in the lichen thallus. These endofungi live and coevolve lichens are known for synthesizing secondary metabolites novel structures diverse chemical skeletons making them unexplored microbial community great interest. As part our search new phytoprotectants, this work, we studied endolichenic fungus Xylaria sp. isolated from Hypogymnia tubulosa, which grows as epiphyte on bark endemic Canarian tree Pinus canariensis. From extract liquid fermentation, two unreported piliformic derivatives, (+)-9-hydroxypiliformic acid (1) (+)-8-hydroxypiliformic (2), along four previously reported compounds, (+)-piliformic (3), hexylaconitic A anhydride (4), 2-hydroxyphenylacetic (5), 4-hydroxyphenylacetic (6). Their were elucidated based NMR HRESIMS data. The compounds tested their insect antifeedant (Myzus persicae, Rhopalosiphum padi, Spodoptera littoralis), antifungal (Alternaria alternata, Botrytis cinerea, Fusarium oxysporum), nematicidal (Meloidogyne javanica), phytotoxic effects mono- dicotyledonous plant models (Lolium perenne Lactuca sativa). Compounds 4, 5, 6 effective antifeedants against M. persicae 4 was also active R. padi. Moreover, 3 showed activity B. cinerea only nematicidal. had a strong effect L. sativa growth, 3, 5 identified agents, while at low concentrations stimulated root growth.

Язык: Английский

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Iron-Catalyzed Hydrobenzylation: Stereoselective Synthesis of (−)-Eugenial C

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(29), С. 15714 - 15720

Опубликована: Июль 12, 2023

Metal-hydride hydrogen atom transfer (MHAT) has emerged as a useful tool to form quaternary carbons from alkenes via hydrofunctionalization. Methods date that cross-couple with sp3 partners rely on heterobimetallic catalysis merge the two cycles. Here, we report an iron-only cross-coupling putative MHAT/SH2 steps solves key stereochemical problem in synthesis of meroterpenoid eugenial C and obviates need for nickel. The concise benefits conformationally locked o,o′-disubstituted benzyl bromide locally sourced chiral pool terpene coupling partner.

Язык: Английский

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Hydrogen-bond-acceptor ligands enable distal C(sp3)–H arylation of free alcohols

Nature, Год журнала: 2023, Номер 622(7981), С. 80 - 86

Опубликована: Сен. 6, 2023

Язык: Английский

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Diversification of pharmaceutical molecules via late-stage C(sp2)–H functionalization

Green Synthesis and Catalysis, Год журнала: 2023, Номер 4(2), С. 104 - 123

Опубликована: Янв. 2, 2023

C–H late-stage functionalization has gradually become a powerful approach for the rapid optimization of lead compounds' bioactivity. Significant advances in this field have been achieved past few years, mainly, system (hetero)aryl activation owing to importance moiety pharmaceutical. In review, we described selected recent examples how developed intermolecular C(sp2)–H methodologies involving diverse techniques diversify pharmaceutical molecules late stage.

Язык: Английский

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Direct C–H Hydroxylation of N-Heteroarenes and Benzenes via Base-Catalyzed Halogen Transfer

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(14), С. 9755 - 9767

Опубликована: Март 26, 2024

Hydroxylated (hetero)arenes are valued in many industries as both key constituents of end products and diversifiable synthetic building blocks. Accordingly, the development reactions that complement address limitations existing methods for introduction aromatic hydroxyl groups is an important goal. To this end, we apply base-catalyzed halogen transfer (X-transfer) to enable direct C–H hydroxylation mildly acidic N-heteroarenes benzenes. This protocol employs alkoxide base catalyze X-transfer from sacrificial 2-halothiophene oxidants aryl substrates, forming SNAr-active intermediates undergo nucleophilic hydroxylation. Key process use 2-phenylethanol inexpensive hydroxide surrogate that, after substitution rapid elimination, provides hydroxylated arene styrene byproduct. Use simple 2-halothiophenes allows 6-membered 1,3-azole derivatives, while a rationally designed 2-halobenzothiophene oxidant extends scope electron-deficient benzene substrates. Mechanistic studies indicate reversible, suggesting deprotonation, halogenation, steps operate synergy, manifesting unique selectivity trends not necessarily dependent on most position. The utility method further demonstrated through streamlined target molecule syntheses, examples regioselectivity contrast alternative methods, scalable recycling thiophene oxidants.

Язык: Английский

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Advancing Heterogeneous Organic Synthesis With Coordination Chemistry‐Empowered Single‐Atom Catalysts

Advanced Materials, Год журнала: 2024, Номер unknown

Опубликована: Сен. 18, 2024

Abstract For traditional metal complexes, intricate chemistry is required to acquire appropriate ligands for controlling the electron and steric hindrance of active centers. Comparatively, preparation single‐atom catalysts much easier with more straightforward effective accesses arrangement control The presence coordination atoms or neighboring functional on supports' surface ensures stability single‐atoms their interactions individual substantially regulate performance Therefore, collaborative interaction between surrounding environment enhances initiation reaction substrates formation transformation crucial intermediate compounds, which imparts significant catalytic efficacy, rendering them a valuable framework investigating correlation structure activity, as well mechanism in organic reactions. Herein, comprehensive overviews both homogeneous complexes reactions are provided. Additionally, reflective conjectures about advancement synthesis also proposed present reference later development.

Язык: Английский

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C–H Glycosylation of Native Carboxylic Acids: Discovery of Antidiabetic SGLT-2 Inhibitors

ACS Central Science, Год журнала: 2023, Номер 9(6), С. 1129 - 1139

Опубликована: Июнь 9, 2023

C-Glycosides are critical motifs embedded in many bioactive natural products. The inert C-glycosides privileged structures for developing therapeutic agents owing to their high chemical and metabolic stability. Despite the comprehensive strategies tactics established past few decades, highly efficient C-glycoside syntheses via C-C coupling with excellent regio-, chemo-, stereoselectivity still needed. Here, we report Pd-catalyzed glycosylation of C-H bonds promoted by weak coordination native carboxylic acids without external directing groups install various glycals structurally diverse aglycon parts. Mechanistic evidence points participation a glycal radical donor reaction. method has been applied wide range substrates (over 60 examples), including marketed drug molecules. Natural product- or drug-like scaffolds compelling bioactivities have constructed using late-stage diversification strategy. Remarkably, new potent sodium-glucose cotransporter-2 inhibitor antidiabetic potential discovered, pharmacokinetic/pharmacodynamic profiles molecules changed our approach. developed here provides powerful tool efficiently synthesizing facilitate discovery.

Язык: Английский

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Nondirected Pd-Catalyzed C–H Perdeuteration and meta-Selective Alkenylation of Arenes Enabled by Pyrazolopyridone Ligands

ACS Catalysis, Год журнала: 2023, Номер 13(7), С. 4042 - 4052

Опубликована: Март 16, 2023

The development of ligands and the elucidation their roles in catalytic cycle are key to achieving high efficiency selectivity nondirected transition-metal-catalyzed C–H functionalization. In particular, careful ligand design can enable functionalization previously inaccessible substrate positions, which lead regiodivergent transformations common reactants. this study, a series pyrazolopyridone (PzPyOH) that be easily prepared single step was developed for Pd-catalyzed perdeuteration meta-selective alkenylation arenes. system, 2-pyridone moiety incorporated function as an internal base, facilitating cleavage rendering activation reversible, even at challenging sp2 bonds, thus enabling perdeuteration. addition, reversible bonds implies site is determined during migratory insertion reaction, thereby preferentially functionalizing meta-positions rather than typically more reactive ortho- para-positions anisole derivatives. Further, electronic structural properties pyrazole provide flexibility binding Pd, facile coordination alkene coupling partner alkenylation. process, hydrogen bonding between pyridone acetate crucial stabilize intermediates, allowing different types modes, including L,L- L,X-type bidentate monodentate binding. Kinetic computational studies support proposed mechanisms alkenylation, findings reveal factors functionalization, will useful further pyrazole- pyridone-containing transition metal catalysis.

Язык: Английский

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A tautomerized ligand enabled meta selective C–H borylation of phenol

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Окт. 30, 2023

Remote meta selective C-H functionalization of aromatic compounds remains a challenging problem in chemical synthesis. Here, we report an iridium catalyst bearing bidentate pyridine-pyridone (PY-PYRI) ligand framework that efficiently catalyzes this borylation reaction. We demonstrate the developed concept can be employed to introduce boron functionality at remote position phenols, phenol containing bioactive and drug molecules, which was extraordinary challenge. Moreover, have demonstrated method also applied for C6 indole derivatives including tryptophan key synthetic precursor total synthesis Verruculogen Fumitremorgin A alkaloids. The inspiration catalytic started from O-Si secondary interaction, by means several more detailed control experiments computational investigations revealed unprecedented Bpin shift occurs during transformation bis(boryl) complex tris(boryl) complex, eventually selectivity dispersion between designed steering silane group.

Язык: Английский

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