Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(8), С. 4237 - 4352

Опубликована: Янв. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

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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Energy-transfer-induced [3+2] cycloadditions of N–N pyridinium ylides

Nature Chemistry, Год журнала: 2023, Номер 15(8), С. 1091 - 1099

Опубликована: Июнь 26, 2023

Язык: Английский

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Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(4), С. 2748 - 2756

Опубликована: Янв. 12, 2024

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated great potential non-natural photoenzymes, all transformations are initiated by single-electron reduction substrate, with only one notable exception. Herein, we report an oxidation-initiated enantioselective hydrosulfonylation olefins using novel mutant gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known systems, our approach does not rely formation electron donor–acceptor complex between substrates and enzyme cofactor simplifies reaction system obviating addition regeneration mixture. More importantly, GluER variant exhibits high reactivity broad substrate scope. Mechanistic studies support proposed mechanism reveal that tyrosine-mediated HAT process is involved.

Язык: Английский

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Photoinduced Regiodivergent and Enantioselective Cross-Coupling of Glycine Derivatives with Hydrocarbon Feedstocks

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Regiodivergent asymmetric synthesis represents a transformative strategy for the efficient generation of structurally diverse chiral products from single set starting materials, significantly enriching their enantiomeric composition. However, design radical-mediated regiodivergent and enantioselective reactions that can accommodate wide range functional groups substrates has posed significant challenges. The obstacles primarily lie in switching regioselectivity achieving high enantiodiscrimination, especially when dealing with high-energy intermediates. To address these issues, we have developed new catalytic system integrates photoinduced hydrogen atom transfer (HAT) copper catalysis, involving fine-tuning ligands, additives, other reaction parameters. facilitates cross-couplings between N-aryl glycine ester/amide derivatives abundant hydrocarbon feedstocks through strong C(sp3)–H bond activation. This approach allows controlled stereoselective formation C(sp3)–C(sp3) C(sp3)–N bonds, yielding rich variety C- or N-alkylated esters amides commendable yields (up to 92% yield), exclusive regioselectivities (typically >20:1 rr), enantioselectivities 96% ee). Our methodology not only provides promising avenue incorporation alkyl functionalities onto specific sites biologically molecules but also offers practical while simultaneously induction within photochemical reactions.

Язык: Английский

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Photoredox-Catalyzed Alkene Acylesterification with Acyloxime Esters via C–C and Tertiary C–O Bond Formation

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

We describe an efficient acyl esterification method for alkenes utilizing acyloxime esters as bifunctional reagents featuring radical acylation and congested C–O bond formation. This approach is characterized by mild photoredox conditions, high step atom economy, a broad substrate scope, excellent regioselectivity. A variety of valuable α-acyl hindered alcohol esters, including those obtained via gram-scale synthesis late-stage functionalization pharmaceutical molecules, were presented, demonstrating its synthetic potential practicability.

Язык: Английский

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Photocatalytic 1,2-Iminosulfonylation and Remote 1,6-Iminosulfonylation of Olefins

Organic Letters, Год журнала: 2023, Номер 25(10), С. 1742 - 1747

Опубликована: Март 8, 2023

A new class of iminosulfonylation reagents were developed and extensively used in the 1,2-iminosulfonylation various olefins. Olefins containing bioactive molecules, such as indomethacin, gemfibrozil, clofibrate, fenbufen, afforded desired products synthetically useful yields. Furthermore, first remote 1,6-iminosulfonylation alkenes was realized by using oxime ester bifunctionalization reagents. Overall, more than 40 structurally diverse β-imine sulfones obtained moderate to excellent

Язык: Английский

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Photoinduced difunctionalization with bifunctional reagents containing N-heteroaryl moieties

Science China Chemistry, Год журнала: 2023, Номер 66(6), С. 1688 - 1700

Опубликована: Май 10, 2023

Язык: Английский

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Photochemical Alkene Trifluoromethylimination Enabled by Trifluoromethylsulfonylamide as a Bifunctional Reagent

Organic Letters, Год журнала: 2023, Номер 25(12), С. 2129 - 2133

Опубликована: Март 21, 2023

Herein, we disclose a facile and versatile trifluoromethylimination of alkene with rationally designed N-(diphenylmethylene)-1,1,1-trifluoromethanesulfonamide as bench-stable readily accessible carboamination reagent. Enabled by an energy transfer (EnT) process, array alkenes were able to be facilely CF3-iminated under metal-free photocatalytic conditions. The mild reaction conditions good functional group compatibility render this protocol highly valuable for the difunctionalization olefins structural complexity diversity.

Язык: Английский

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Divergent Synthesis of F- and CF₃-Containing N-Fused Heterocycles Enabled by Fragmentation Cycloaddition of β-CF₃-1,3-Enynes with N-Aminopyridiniums Ylides

Organic Letters, Год журнала: 2024, Номер 26(6), С. 1255 - 1260

Опубликована: Фев. 7, 2024

The two novel cyclization modes of β-CF

Язык: Английский

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