Catalysis in the Excited State: Bringing Innate Transition Metal Photochemistry into Play

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4665 - 4680

Published: March 5, 2025

Transition metal catalysis is an indispensable tool for organic synthesis that has been harnessed, modulated, and perfected many decades by careful selection of centers ligands, giving rise to synthetic methods with unparalleled efficiency chemoselectivity. Recent developments have demonstrated how light irradiation can also be recruited as a powerful dramatically alter the outcome catalytic reactions, providing access innovative pathways remarkable potential. In this context, adoption photochemical conditions mainstream strategy drive reactions unveiled exciting opportunities exploit rich excited-state framework transition metals applications. This Perspective examines advances in application complexes standalone photocatalysts, exploiting innate reactivity their excited states beyond common use photoredox catalysts. An account relevant examples dissected provide discussion on electronic reorganization, orbitals involved, associated different types states. analysis aims practitioners fundamental principles guiding strategies understand, design, apply light-activation homogeneous synthesis.

Language: Английский

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General Regio- and Diastereoselective Allylic C–H Oxygenation of Internal Alkenes

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(27), P. 18218 - 18223

Published: June 26, 2024

Branched allylic esters and carboxylates are fundamental motifs prevalent in natural products drug molecules. The direct C-H oxygenation of internal alkenes represents one the most straightforward approaches, bypassing requirement for an leaving group as classical Tsuji-Trost reaction. However, current methods suffer from limited scope─often accompanied by selectivity issues─thus hampering further development. Herein we report a photocatalytic platform general solution to these problems, enabling coupling diverse with carboxylic acids, alcohols, other

Language: Английский

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Catalytic Asymmetric Cascade Dearomatization of Indoles via a Photoinduced Pd‐Catalyzed 1,2‐Bisfunctionalization of Butadienes

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(26)

Published: April 20, 2024

Photoinduced Pd-catalyzed bisfunctionalization of butadienes with a readily available organic halide and nucleophile represents an emerging attractive method to assemble versatile alkenes bearing various functional groups at the allylic position. However, enantiocontrol and/or diastereocontrol in C-C or C-X bond-formation step have not been solved due open-shell process. Herein, we present cascade asymmetric dearomatization reaction indoles via photoexcited 1,2-biscarbonfunctionalization 1,3-butadienes, wherein control on both electrophile part is achieved for first time photoinduced butadienes. This delivers structurally novel chiral spiroindolenines two contiguous stereogenic centers high diastereomeric ratios (up >20 : 1 dr) good excellent enantiomeric 97 3 er). Experimental computational studies mechanism confirmed radical pathway involving excited-state palladium catalysis. The alignment non-covalent interactions between substrate catalyst were found be essential stereocontrol.

Language: Английский

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Selective 1,4-syn-Addition to Cyclic 1,3-Dienes via Hybrid Palladium Catalysis

ACS Central Science, Journal Year: 2024, Volume and Issue: 10(6), P. 1191 - 1200

Published: May 15, 2024

1,4-cis-Disubstituted cyclic compounds play a pivotal role in pharmaceutical development, offering enhanced potency and bioavailability. However, their stereoselective modular synthesis remains long-standing challenge. Here, we report an innovative strategy for accessing these structures via mild conditions employing 1,3-dienes/alkyl(aryl)halides amines. This procedure exhibits wide substrate scope that tolerates various functional groups. The utility of this method is demonstrated the efficient TRPV6 inhibitor, CFTR modulator, other bioactive molecules. Combined experimental computational studies suggest hybrid palladium-catalyzed radical-polar crossover mechanism crucial achieving exceptional 1,4-syn-addition selectivity (dr > 20:1).

Language: Английский

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Dynamic Kinetic Activation of Aziridines Enables Radical-Polar Crossover (4 + 3) Cycloaddition with 1,3-Dienes

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

Published: Jan. 10, 2025

The cycloaddition of aziridines with unsaturated compounds is a valuable method for synthesizing nitrogen heterocycles. However, this process predominantly substrate-controlled, posing significant challenges in regulating the regioselectivity C–N bond cleavage. In study, we report nickel-catalyzed dynamic kinetic activation strategy that enables catalyst-controlled aziridines. Various types aziridines, including 2-phenyl, 2-carbonyl, 2-alkyl, and disubstituted consistently cleave their more sterically hindered bonds to generate 1,3-radical anion intermediates. These intermediates participate highly regioselective 1,4-Heck/allylic substitution cascade aromatic branched 1,3-dienes, resulting radical-polar crossover (4 + 3) produces seven-membered azepine products. This approach not only complements traditional dipolar cycloaddition, which typically act as zwitterionic 1,3-dipoles, but also introduces an unusual mode 1,3-dienes. Experimental investigations density functional theory (DFT) calculations provide insight into reaction mechanism.

Language: Английский

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Copper-Initiated Regiodivergent Chloropentafluorosulfanylation of 1,3-Enynes under Substrate Control

Organic Letters, Journal Year: 2024, Volume and Issue: 26(23), P. 5049 - 5054

Published: June 4, 2024

A copper-catalyzed regiodivergent chloropentafluorosulfanylation strategy for 1,3-enynes using SF

Language: Английский

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Ketyl Radical Generation by Photoexcited Palladium and Development of Organopalladium-Type Reactions

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(7), P. 5269 - 5274

Published: March 25, 2024

Enabling reactions of traditional substrates that are inert to Pd catalysts has the potential for further advancements in field chemistry. In this study, we developed a method generating ketyl radicals through reaction photoexcited species with ketones. Upon subsequent olefins, generated yielded Pd-specific reductive and Heck-type coupling products. Mechanistic studies indicated proposed radical generation exhibits characteristics distinct from those methods such as SmI2 reduction photoredox-catalyzed reactions.

Language: Английский

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Photoinduced Pd‐Catalyzed Direct Sulfonylation of Allylic C–H Bonds

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 64(1)

Published: Sept. 17, 2024

Allylic sulfones are valuable motifs due to their medicinal and biological significance versatile chemical reactivities. While direct allylic C-H sulfonylation represents a straightforward desirable approach, these methods primarily restricted terminal alkenes, leaving the engagement of internal counterparts formidable challenge. Herein we report photocatalytic approach that accommodates both cyclic acyclic alkenes with diverse substitution patterns electronic properties. Importantly, obtained can be readily diversified into wide range products, thus enabling formal alkene transposition all-carbon quaternary center formation through sequential functionalization.

Language: Английский

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Illuminating Palladium Catalysis

Accounts of Chemical Research, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

ConspectusThe past decade has witnessed significant advancements of visible-light-induced photocatalysis, establishing it as a powerful and versatile tool in organic synthesis. The major focus this field centered on the development methodologies that either rely solely photocatalysts or combine photocatalysis with other catalytic methods, such transition metal catalysis, to address broader more diverse array transformations. Within rapidly evolving area, subfield we refer garnered attention due its growing impact mechanistic uniqueness. A distinguishing feature is dual functionality single complex, which not only acts photocatalyst initiate photochemical processes but also functions traditional catalyst, facilitating key bond-breaking bond-forming events. As such, an exogenous required photocatalysis. However, implications harnessing both excited- ground-state reactivities complex can extend beyond simplification. One most compelling aspects area photoexcited complexes exhibit unique inaccessible through conventional thermal photocatalytic approaches. These distinct be leveraged accomplish novel transformations by engaging entirely different substrate pool unlocking new known substrates.In 2016, our group pioneered use phosphine-ligated palladium catalysts upon visible-light irradiation engage substrates radical reactions. In initial discovery, showed photoexcitation redirect well-established oxidative addition Pd(0) into aryl iodides toward unprecedented process, generating hybrid Pd(I) species. We subsequently extended strategy formation alkyl radicals from halides. reactive intermediates have been harnessed wide variety transformations, including desaturation, Heck reactions, alkene difunctionalization cascades, among others.Seeking further expand avenue, achieved first example asymmetric context allylic C–H amination, where catalyst now plays triple duty additionally controlling stereochemical outcome reaction. parallel reaction established diazo compounds, strained molecules, electron-deficient alkenes serve precursors halides redox-active esters. Notably, engagement made possible photoinduced hydricity enhancement Pd–H species, representing mode reactivity.This Account presents discovery organized type explored. Given rapid progress field, anticipate will provide readers guiding principles inspiration for designing developing efficient

Language: Английский

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The Construction of Highly Substituted Piperidines via Dearomative Functionalization Reaction

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(49)

Published: Oct. 20, 2023

Nitrogen heterocycles play a vital role in pharmaceuticals and natural products, with the six-membered aromatic aliphatic architectures being commonly used. While synthetic methods for N-heterocycles are well-established, synthesis of their functionalized analogues, particularly piperidine derivatives, poses significant challenge. In that regard, we propose stepwise dearomative functionalization reaction construction highly decorated derivatives diverse functional handles. We also discuss challenges related to site-selectivity, regio- diastereoselectivity, provide insights into mechanism through mechanistic studies density theory computations.

Language: Английский

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