Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 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.

Language: Английский

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Late-Stage C–H Functionalization of Azines

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7655 - 7691

Published: May 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.

Language: Английский

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

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(8), P. 1091 - 1099

Published: June 26, 2023

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2748 - 2756

Published: Jan. 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.

Language: Английский

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

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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

Organic Letters, Journal Year: 2023, Volume and Issue: 25(10), P. 1742 - 1747

Published: March 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

Language: Английский

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Photoinduced difunctionalization with bifunctional reagents containing N-heteroaryl moieties

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(6), P. 1688 - 1700

Published: May 10, 2023

Language: Английский

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Photochemical Alkene Trifluoromethylimination Enabled by Trifluoromethylsulfonylamide as a Bifunctional Reagent

Organic Letters, Journal Year: 2023, Volume and Issue: 25(12), P. 2129 - 2133

Published: March 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.

Language: Английский

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Unlocking the Potential of β-Fragmentation of Aminophosphoranyl Radicals for Sulfonyl Radical Reactions

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(26), P. 14510 - 14518

Published: June 20, 2023

Exploiting β-scission in aminophosphoranyl radicals for radical-mediated transformations has been a longstanding challenge. In this study, we investigated the untapped potential of β-fragmentation by leveraging unique properties P-N bond and substituents P(III) reagents. Our approach carefully considers factors such as cone angle electronic phosphine employs density functional theory (DFT) calculations to probe structural molecular orbital influence. We successfully induced through N-S cleavage under visible light mild conditions, generating range sulfonyl derived from pyridinium salts via photochemical activity electron donor-acceptor (EDA) complexes. This innovative synthetic strategy exhibits broad applicability, including late-stage functionalization, paves way valuable reactions, alkene hydrosulfonylation, difunctionalization, pyridylic C-H sulfonylation.

Language: Английский

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