Transition-Metal-Catalyzed Divergent C–H Functionalization of Five-Membered Heteroarenes

Accounts of Chemical Research, Год журнала: 2021, Номер 54(24), С. 4518 - 4529

Опубликована: Дек. 10, 2021

Conversion of common reactants to diverse products is a key objective organic syntheses. Recent developments in transition-metal-catalyzed C-H functionalization have increased the interest such conversions. Both position and type substituent can be varied, allowing systematic diversification structural cores. Because five-membered heteroarenes (pyrazole, imidazole, thiazole, pyrrole, thiophene) are ubiquitous pharmaceuticals functional materials, selective these heterocyclic cores facilitates both optimization their physicochemical properties streamlining preparation. In addition, parent forms heterocycles more readily available inexpensive than any other derivatives families. Hence, nondirected highly desirable. Although various regioselective reactions been developed, many them target most reactive site; hence, except for some extensively studied arylation reactions, regiodivergent two or sites has limited.This Account summarizes our work on regiodivergent, with alkenes alkynes. These unsaturated hydrocarbons available, all composing atoms incorporated into high atom efficiency. Furthermore, installed alkenyl groups transformed useful groups. To achieve comparable selectivity that observed traditional electrophilic reagents strong bases, transition metal catalytic system was carefully devised streamlined synthesis. A judicious choice metals, ligands, acid base additives, solvents orchestrates divergent transformations using electronic steric effects heteroarenes. cleavage rate- site-selectivity-determining step cases, subsequent steps involving formation C-C bonds often critical steps. For step, modulating catalysts make allows preferential alkenylation at nucleophilic position. presence an internal exploited concerted metalation-deprotonation acidic bond offers alternative regioselectivity. we developed own ligand based conformationally rigid pyrazolonaphthyridine scaffold enables aerobic control. We showed further extended chemodivergent norbornene derivatives. Depending whether palladacycle formed, selectively undergo 1:2 annulation three-component azoles through Pd-norbornene adducts Catellani 2:1 intermediates.Other research also contributed development investigations ranging from pioneering studies early days recent new ligands. discussed context. approaches provide access systematically varied substituents. believe systems mechanistic insights gained will enrich fields beyond

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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Palladium(II)‐Catalyzed Nondirected Late‐Stage C(sp²)−H Deuteration of Heteroarenes Enabled Through a Multi‐Substrate Screening Approach

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(27)

Опубликована: Март 21, 2024

The importance of deuterium labelling in a variety applications, ranging from mechanistic studies to drug-discovery, has spurred immense interest the development new methods for its efficient incorporation organic, and especially bioactive molecules. five-membered heteroarenes at center this work are ubiquitous motifs molecules these compounds therefore highly desirable. However, profound differences chemical properties encountered between different hamper single set broadly applicable reaction conditions, often necessitating separate optimization campaign given type heteroarene. In study we describe use multi-substrate screening approach identify optimal conditions classes minimal number reactions. Using approach, four sets complementary derived our dual ligand-based palladium catalysts nondirected C(sp

Язык: Английский

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Late‐Stage C−H Activation of Drug (Derivative) Molecules with Pd(ll) Catalysis

Chemistry - A European Journal, Год журнала: 2023, Номер 29(71)

Опубликована: Окт. 17, 2023

Abstract This review comprehensively analyses representative examples of Pd(II)‐catalyzed late‐stage C−H activation reactions and demonstrates their efficacy in converting bonds at multiple positions within drug (derivative) molecules into diverse functional groups. These transformative hold immense potential medicinal chemistry, enabling the efficient selective functionalization specific sites molecules, thereby enhancing pharmacological activity expanding scope candidates. Although notable articles have focused on drug‐like using transition‐metal catalysts, reviews specifically focusing Pd(II) catalysts are required owing to prominence as most widely utilized metal for ability introduce a myriad groups bonds. The utilization Pd‐catalyzed methodologies impressive success introducing various groups, such cyano (CN), fluorine (F), chlorine (Cl), aromatic rings, olefin, alkyl, alkyne, hydroxyl with high regioselectivity functional‐group tolerance. breakthroughs serve invaluable tools discovery development, offering strategic options optimize candidates drive exploration innovative therapeutic solutions.

Язык: Английский

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Palladium(II) NCS‐Pincer Complexes Mediated Regioselective Cross Dehydrogenative Alkenation of 2‐Arylthiophenes

ChemCatChem, Год журнала: 2024, Номер 16(15)

Опубликована: Март 18, 2024

Abstract In this report, we have synthesized two new NCS pincer ligands by the Schiff base reaction of 3‐((phenylthio)methoxy)benzaldehyde ( P ) with alkyl amines t butylamine L1 and 1‐adamantylamine L2 )). The palladium complexes butylamine= C1 1‐adamantylamine= C2 these were their PdCl 2 (CH 3 CN) precursor. newly characterized using various analytical spectroscopic techniques such as 1 H, 13 C{ H} Nuclear Magnetic Resonance (NMR), Ultraviolet–visible (UV‐Visible), Fourier Transform Infrared (FTIR) Spectroscopy, High‐Resolution Mass Spectrometry (HRMS). structure ligand its coordination mode precursor studied help single‐crystal X‐ray diffraction. showed distorted square planar geometry around center. used catalysts for regioselective cross‐dehydrogenative alkenation 2‐arylthiophene derivatives. complex , where sterically bulky adamantyl is part side arm a higher yield reaction. Only 2.5 mol% catalyst loading was sufficient to achieve 74–95 % yields desired products excellent functional group tolerance under mild conditions. poisoning experiments (PPh Hg) homogeneous nature catalytic process. plausible mechanism proposed based on control time‐dependent HRMS studies.

Язык: Английский

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Photoredox-Cobaloxime Catalysis for Selective Oxidative Dehydrogenative [4+2] Annulation of Imidazo-Fused Heterocycles with Alkenes

Organic Letters, Год журнала: 2024, Номер 26(13), С. 2529 - 2534

Опубликована: Март 21, 2024

A selective oxidative [4+2] annulation of alkenes with imidazo-fused heterocycles has been developed by using the synergistic combination photoredox and cobaloxime catalysts. It allows facile access to various imidazole-fused polyaromatic scaffolds accompanied H2 evolution. This protocol features high regioselectivity as well a broad substrate scope. Detailed mechanistic studies indicate that twice electron/H transfer processes facilitated this catalytic system achieve π-extension alkenes.

Язык: Английский

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Five-membered ring systems: pyrroles and benzo analogs

Progress in heterocyclic chemistry, Год журнала: 2023, Номер unknown, С. 155 - 207

Опубликована: Янв. 1, 2023

Язык: Английский

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Palladium‐catalyzed CH acetoxylation of arenes using a pyrazolonaphthyridine ligand

Bulletin of the Korean Chemical Society, Год журнала: 2022, Номер 43(10), С. 1173 - 1176

Опубликована: Авг. 5, 2022

Abstract Herein, Pd‐catalyzed CH acetoxylation reactions of arenes are developed using a pyrazolonaphthyridine ligand. In the presence iodomesitylene diacetate as oxidant, electron‐deficient ligand facilitates activation electron‐rich positions while preventing formation Pd black via bidentate binding. Although both acetic acid and hexafluoroisopropanol employed for directing group‐assisted reactions, latter proved to be more efficient nondirected reaction with nitrogen

Язык: Английский

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Nondirected Pd-catalyzed aerobic C–H alkenylation of ruthenocene and ferrocene

Chemical Communications, Год журнала: 2022, Номер 58(77), С. 10809 - 10812

Опубликована: Янв. 1, 2022

Pd-catalyzed alkenylations of metallocenes via C-H activation were developed using electronically tunable pyrazolonaphthyridine (PzNPy) ligands. Ferrocene was alkenylated the most electron-deficient ligand in series, whereas less reactive ruthenocene needed balancing electrophilicity and stability catalysts. Various alkenes installed, allowing fine-tuning redox potentials.

Язык: Английский

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Synergistic Palladium/Silver/Ligand Catalysis for C−H Alkenylation of 2,1,3‐Benzofused Heterodiazoles

Advanced Synthesis & Catalysis, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 18, 2024

Abstract The combination of palladium and silver complexes has emerged as a bimetallic catalytic system in C−H activation, frequently outperforming palladium‐only systems. Beyond the conventional roles (I) salts serving oxidants, halide scavengers, Lewis acids, Pd−Ag synergism been shown to facilitate cleavage. In this study, we explore incorporation pyrazolopyridone (PzPyOH) ligand into system, which together promote both cleavage migratory insertion processes. This synergistic approach enables dehydrogenative alkenylations at C4 position 2,1,3‐benzothiadiazole, 2,1,3‐benzoxadiazole, 2,1,3‐benzotriazole with alkenes. These results demonstrate potential combining novel ligands heterobimetallic systems other elementary steps beyond cleavage, suggesting their broader applicability functionalization.

Язык: Английский

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