Enhanced Reactivity of Acridinium Perchlorate: Harnessing Redox Mediators for Trace Chloride Activation in Hydrogen Atom Transfer Photocatalysis DOI

Mingyue Wu,

Zugen Wu, Hwee Ting Ang

et al.

ACS Catalysis, Journal Year: 2024, Volume and Issue: 14(12), P. 9364 - 9373

Published: June 5, 2024

Acridinium perchlorates and tetrafluoroborates are commonly employed photocatalysts with similar photophysical characteristics. Nevertheless, perchlorate salts consistently exhibit superior catalytic performance relative to their tetrafluoroborate counterparts. In a serendipitous discovery, we unveiled the latent potential of trace chloride anions originating from acridinium salts. When coupled redox mediators like diphenyl ether or biphenyl, displayed remarkable hydrogen atom transfer (HAT) catalysis capabilities. This innovative approach enabled efficient activation diverse range unactivated C–H bonds, especially primary C(sp3)–H via Giese additions Minisci-type cross-dehydrogenative coupling reactions. Our system stands as one most HAT systems for bond activation, showcasing substrate diversity. Additionally, use stop-flow microtubing (SFMT) reactor enhanced reaction efficiency, enabling gram-scale synthesis seamless transition continuous flow processes practical-scale production.

Language: Английский

Synthetic Applications of Photocatalyzed Halogen‐Radical Mediated Hydrogen Atom Transfer for C−H Bond Functionalization DOI Creative Commons
Stefano Bonciolini, Timothy Noël, Luca Capaldo

et al.

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(34)

Published: May 13, 2022

Abstract The opportunity to activate C(sp 3 )−H bonds via homolytic cleavage by means of halogen radicals has long been disregarded in synthetic endeavors due the unpredictable selectivity. Nowadays, photocatalysis established itself as a method choice for generation such reactive intermediates under mild conditions. This Minireview collects recent examples showcasing how photocatalytic manifolds have used tame aggressive Hydrogen Atom Transfer (HAT) purposes. In last section this work, we address site‐selectivity issues posed methodology and show it can be guided through judicious reaction

Language: Английский

Citations

71
Regioselective aliphatic C–H functionalization using frustrated radical pairs DOI
Zhipeng Lu, Minsoo Ju, Yi Wang

et al.

Nature, Journal Year: 2023, Volume and Issue: 619(7970), P. 514 - 520

Published: July 5, 2023

Language: Английский

Citations

68
Resurgence and advancement of photochemical hydrogen atom transfer processes in selective alkane functionalizations DOI Creative Commons
Liang Chang, Shun Wang, Qing An

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(25), P. 6841 - 6859

Published: Jan. 1, 2023

The selective functionalization of alkanes has long been recognized as a prominent challenge and an arduous task in organic synthesis. Hydrogen atom transfer (HAT) processes enable the direct generation reactive alkyl radicals from feedstock have successfully employed industrial applications such methane chlorination process,

Language: Английский

Citations

67
Rapid Access to 2-Substituted Bicyclo[1.1.1]pentanes DOI
Olivia L. Garry, Michael Heilmann, Jingjia Chen

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(5), P. 3092 - 3100

Published: Jan. 25, 2023

The replacement of aryl rings with saturated carbocyclic structures has garnered significant interest in drug discovery due to the potential for improved pharmacokinetic properties upon substitution. In particular, 1,3-difunctionalized bicyclo[1.1.1]pentanes (BCPs) have been widely adopted as bioisosteres parasubstituted arene rings, appearing a number lead pharmaceutical candidates. However, despite value 2-substituted BCPs replacements ortho- or meta-substituted general and rapid syntheses these scaffolds remain elusive. Current approaches rely on installation bridge substituent prior BCP core construction, leading lengthy step counts often nonmodular sequences. While challenging, direct functionalization strong C-H bonds would offer more streamlined pathway diverse BCPs. Here, we report generalizable synthetic linchpin strategy via radical abstraction core. Through mild generation hydrogen atom abstractor, rapidly synthesize novel linchpins one pot. These then serve common precursors complex BCPs, allowing one-step access previously inaccessible electrophile nucleophile fragments at 2-position two new metallaphotoredox protocols. Altogether, this platform enables expedient synthesis four analogues, all which show similar compared their aryl-containing equivalents, demonstrating development.

Language: Английский

Citations

61
Site- and enantioselective cross-coupling of saturated N-heterocycles with carboxylic acids by cooperative Ni/photoredox catalysis DOI Creative Commons
Xiaomin Shu,

De Zhong,

Qian Huang

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Jan. 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.

Language: Английский

Citations

57
Radical Polarity DOI
Jacob J. A. Garwood, Andrew D. Chen, David A. Nagib

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 3, 2024

The polarity of a radical intermediate profoundly impacts its reactivity and selectivity. To quantify this influence predict effects, the electrophilicity/nucleophilicity >500 radicals has been calculated. This database open-shell species entails frequently encountered synthetic intermediates, including centered at sp

Language: Английский

Citations

36
Visible-Light-Catalyzed Tandem Radical Addition/1,5-Hydrogen Atom Transfer/Cyclization of 2-Alkynylarylethers with Sulfonyl Chlorides DOI
Long Li,

Jiao‐Zhe Li,

Yong-Bin Sun

et al.

Organic Letters, Journal Year: 2022, Volume and Issue: 24(25), P. 4704 - 4709

Published: June 20, 2022

A novel visible-light-catalyzed tandem radical addition/1,5-hydrogen atom transfer/cyclization cascade of 2-alkynylarylethers with sulfonyl chlorides in 2-methyltetrahydrofuran was developed under photocatalyst- and additive-free conditions. This reaction relies on unique energy transfer solvent-radical relay strategies to generate radicals for the preparation a series sulfonyl-functionalized dihydrobenzofurans moderate high yields catalyzed by visible light or solar radiation.

Language: Английский

Citations

54
The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins DOI Creative Commons
Alberto Luridiana, Daniele Mazzarella, Luca Capaldo

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(18), P. 11216 - 11225

Published: Sept. 1, 2022

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis silyl radical-induced halogen (XAT) subsequently intercepted a nickel catalyst to forge the targeted C(sp3)-C(sp2) C(sp3)-C(sp3) bonds. The mild protocol is fast scalable using flow technology, displays broad functional group tolerance, amenable wide variety medicinally relevant moieties. Mechanistic investigations reveal that ketone catalyst, upon photoexcitation, responsible direct activation silicon-based XAT reagent (HAT-mediated XAT) furnishes radical ultimately involved in turnover catalytic cycle.

Language: Английский

Citations

50
Hydrogen Bonding-Assisted and Nonheme Manganese-Catalyzed Remote Hydroxylation of C–H Bonds in Nitrogen-Containing Molecules DOI
Jie Chen, Wenxun Song, Jinping Yao

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5456 - 5466

Published: Feb. 22, 2023

The development of catalytic systems capable oxygenating unactivated C-H bonds with excellent site-selectivity and functional group tolerance under mild conditions remains a challenge. Inspired by the secondary coordination sphere (SCS) hydrogen bonding in metallooxygenases, reported herein is an SCS solvent strategy that employs 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as strong bond donor to enable remote hydroxylation presence basic aza-heteroaromatic rings low loading readily available inexpensive manganese complex catalyst peroxide terminal oxidant. We demonstrate this represents promising compliment current state-of-the-art protection approaches rely on precomplexation Lewis and/or Brønsted acids. Mechanistic studies experimental theoretical reveal existence between nitrogen-containing substrate HFIP, which prevents deactivation nitrogen binding deactivates atom toward oxygen transfer α-C-H adjacent center H-atom abstraction. Moreover, exerted HFIP has also been demonstrated not only facilitate O-O heterolytic cleavage putative MnIII-OOH precursor generate MnV(O)(OC(O)CH2Br) active oxidant but affect stability activity MnV(O)(OC(O)CH2Br).

Language: Английский

Citations

40
Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer DOI Creative Commons
Filip S. Meger, John A. Murphy

Molecules, Journal Year: 2023, Volume and Issue: 28(16), P. 6127 - 6127

Published: Aug. 18, 2023

The functionalisation of C–H bonds has been an enormous achievement in synthetic methodology, enabling new retrosynthetic disconnections and affording simple equivalents for synthons. Hydrogen atom transfer (HAT) is a key method forming alkyl radicals from substrates. Classic reactions, including the Barton nitrite ester reaction Hofmann–Löffler–Freytag reaction, among others, provided early examples HAT. However, recent developments photoredox catalysis electrochemistry have made HAT powerful tool capable introducing wide range functional groups into bonds. Moreover, greater mechanistic insights stimulated development increasingly site-selective protocols. Site-selectivity can be achieved through tuning electron density at certain using additives, judicious choice reagent, solvent system. Herein, we describe latest methods functionalizing C–H/Si–H/Ge–H indirect between 2018–2023, as well critical discussion reagents, aspects, substrate scopes, background contexts

Language: Английский

Citations

29