Cooperative NHC/Photoredox Catalyzed Ring‐Opening of Aryl Cyclopropanes to 1‐Aroyloxylated‐3‐Acylated Alkanes

Angewandte Chemie International Edition, Год журнала: 2021, Номер 60(48), С. 25252 - 25257

Опубликована: Сен. 28, 2021

Cyclopropanes are an important class of building blocks in organic synthesis. Herein, a ring-opening/arylcarboxylation/acylation cascade reaction for the 1,3-difunctionalization aryl cyclopropanes enabled by cooperative NHC and organophotoredox catalysis is reported. The works on monosubstituted that contrast to heavily investigated donor-acceptor more challenging be difunctionalized. key step radical/radical cross coupling benzylic radical generated photoredox cycle with ketyl from cycle. transformation features metal-free conditions tolerates diverse range functionalities.

Язык: Английский

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Late-Stage C–H Functionalization of Azines

Chemical Reviews, Год журнала: 2023, Номер 123(12), С. 7655 - 7691

Опубликована: Май 3, 2023

Azines, such as pyridines, quinolines, pyrimidines, and pyridazines, are widespread components of pharmaceuticals. Their occurrence derives from a suite physiochemical properties that match key criteria in drug design is tunable by varying their substituents. Developments synthetic chemistry, therefore, directly impact these efforts, methods can install various groups azine C–H bonds particularly valuable. Furthermore, there growing interest late-stage functionalization (LSF) reactions focus on advanced candidate compounds often complex structures with multiple heterocycles, functional groups, reactive sites. Because factors electron-deficient nature the effects Lewis basic N atom, distinct arene counterparts, application LSF contexts difficult. However, have been many significant advances reactions, this review will describe progress, much which has occurred over past decade. It possible to categorize radical addition processes, metal-catalyzed activation transformations occurring via dearomatized intermediates. Substantial variation reaction within each category indicates both rich reactivity heterocycles creativity approaches involved.

Язык: Английский

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Late-stage Functionalization for Improving Drug-like Molecular Properties

Chemical Reviews, Год журнала: 2023, Номер 123(13), С. 8127 - 8153

Опубликована: Июнь 7, 2023

The development of late-stage functionalization (LSF) methodologies, particularly C–H functionalization, has revolutionized the field organic synthesis. Over past decade, medicinal chemists have begun to implement LSF strategies into their drug discovery programs, allowing for process become more efficient. Most reported applications drugs and drug-like molecules been rapidly diversify screening libraries explore structure–activity relationships. However, there a growing trend toward use methodologies as an efficient tool improving molecular properties promising candidates. In this review, we comprehensively reviewed recent progress in emerging area. Particular emphasis is placed on case studies where multiple techniques were implemented generate library novel analogues with improved properties. We critically analyzed current scope improve commented how believe can transform future. Overall, aim provide comprehensive survey tools efficiently properties, anticipating its continued uptake programs.

Язык: Английский

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The promise and pitfalls of photocatalysis for organic synthesis

Chem Catalysis, Год журнала: 2022, Номер 2(3), С. 468 - 476

Опубликована: Фев. 3, 2022

Язык: Английский

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Modular Access to Chiral α-(Hetero)aryl Amines via Ni/Photoredox-Catalyzed Enantioselective Cross-Coupling

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(19), С. 8797 - 8806

Опубликована: Май 3, 2022

Chiral α-aryl N-heterocycles are commonly found in natural products, pharmaceutical agents, and chiral catalysts but remain challenging to access via asymmetric catalysis. Herein, we report a general modular approach for the direct enantioselective α-arylation of saturated azacycles acyclic N-alkyl benzamides nickel/photoredox dual This process exploits hydrogen atom transfer ability photoeliminated chlorine radicals convert corresponding α-amino alkyl that then coupled with ubiquitous inexpensive (hetero)aryl chlorides. These coupling reactions require no oxidants or organometallic reagents, feature feedstock starting materials, broad substrate scope, high enantioselectivities, applicable late-stage diversification medicinally relevant complex molecules. Mechanistic studies suggest nickel catalyst uncommonly plays multiple roles, accomplishing radical generation, capture, cross-coupling, induction.

Язык: Английский

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Photochemistry Journey to Multielectron and Multiproton Chemical Transformation

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(36), С. 16219 - 16231

Опубликована: Сен. 2, 2022

The odyssey of photochemistry is accompanied by the journey to manipulate "electrons" and "protons" in time, space, energy. Over past decades, single-electron (1e-) photochemical transformations have brought marvelous achievements. However, as each photon absorption typically generates only one exciton pair, it exponentially challenging accomplish multielectron proton transformations. multistep differences thermodynamics kinetics urgently require us optimize light harvesting, expedite consecutive electron transfer, interaction catalysts with substrates, coordinate transfer furnish selective bond formations. Tandem catalysis enables orchestrating different events catalytic from subpicoseconds seconds, which facilitates redox chemistries brings consecutive, value-added reactivities. Joint efforts molecular material design, mechanistic understanding, theoretical modeling will bring synthetic opportunities for fuels, fertilizers, chemicals enhanced versatility, efficiency, selectivity, scalability, thus taking better advantage photons (i.e., sunlight) our sustainable society.

Язык: Английский

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Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis

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

Опубликована: Янв. 9, 2023

Abstract Site- and enantioselective cross-coupling of saturated N -heterocycles carboxylic acids—two the most abundant versatile functionalities—to form pharmaceutically relevant α-acylated amine derivatives remains a major challenge in organic synthesis. Here, we report general strategy for highly site- α-acylation with situ-activated acids. This modular approach exploits hydrogen-atom-transfer reactivity photocatalytically generated chlorine radicals combination asymmetric nickel catalysis to selectively functionalize cyclic α-amino C−H bonds presence benzylic, allylic, acyclic α-amino, α-oxy methylene groups. The mild scalable protocol requires no organometallic reagents, displays excellent chemo-, enantioselectivity, is amenable late-stage diversification, including synthesis previously inaccessible Taxol derivatives. Mechanistic studies highlight exceptional versatility chiral catalyst orchestrating (i) catalytic elimination, (ii) alkyl radical capture, (iii) cross-coupling, (iv) induction.

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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Green chemistry meets medicinal chemistry: a perspective on modern metal-free late-stage functionalization reactions

Chemical Society Reviews, Год журнала: 2021, Номер 50(19), С. 10955 - 10982

Опубликована: Янв. 1, 2021

This review summarizes the most recent advances of metal-free late-stage functionalization (LSF) pharmaceutically relevant molecules. Particular emphasis is placed on C – H activation as well use endogenous functional groups.

Язык: Английский

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Asymmetric benzylic C(sp3)−H acylation via dual nickel and photoredox catalysis

Nature Communications, Год журнала: 2021, Номер 12(1)

Опубликована: Июнь 10, 2021

Abstract Asymmetric C(sp 3 )−H functionalization is a persistent challenge in organic synthesis. Here, we report an asymmetric benzylic C−H acylation of alkylarenes employing carboxylic acids as acyl surrogates for the synthesis α-aryl ketones via nickel and photoredox dual catalysis. This mild yet straightforward protocol transforms diverse array feedstock simple alkyl benzenes into highly valuable with high enantioselectivities. The utility this method showcased gram-scale late-stage modification medicinally relevant molecules. Mechanistic studies suggest photocatalytically generated bromine radical can perform cleavage to activate nucleophilic coupling partners which then engage nickel-catalyzed cross-coupling reaction. bromine-radical-mediated activation strategy be also applied enantioselective chloroformate chiral esters.

Язык: Английский

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