Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation

Ferhati, Xhenti; Salas-Cubero, Marina; Garrido, Pablo; Garcı́a-Sanmartı́n, Josune; Guerreiro, Ana; Avenoza, Alberto; Busto, Jesús H.; Peregrina, Jesús M.; Martı́nez, Alfredo; Jiménez‐Moreno, Ester; Bernardes, Gonçalo J. L.; Corzana, Francisco

doi:10.1021/acs.orglett.1c03299

Cited by 3 publications

(2 citation statements)

References 25 publications

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“…The systematic investigation of C–C bond cleavage can be dated to the 1950s when the pioneer Eschenmonser and the protagonist Grob made manifold contributions . Since then, this type of reaction named “Grob fragmentation” has been an instrumental tool to synthesize diverse organic frameworks, which can be applied frequently in both synthetic chemistry and biological chemistry …”

Section: Introductionmentioning

confidence: 99%

Synthesis of (2-(Quinolin-2-yl)phenyl)carbamates by a One-Pot Friedel–Crafts Reaction/Oxidative Umpolung Aza-Grob Fragmentation Sequence

Xie

Long

et al. 2022

J. Org. Chem.

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Utilizing the easily available isatin-based propargyl amines prepared from isatins, terminal alkynes, and anilines, (2-(quinolin-2-yl)phenyl)carbamates were prepared by a one-pot reaction in sequence, combining the gold-catalyzed Friedel−Crafts cyclization, oxidative umpolung aza-Grob fragmentation, and nucleophilic addition. In this process, gold-catalyzed cyclization of isatin-based propargyl amines gave 1′H-spiro[indoline-3,2′-quinolin]-2-ones, which were oxidized in situ by hypervalent iodine via the aza-Grob fragmentation to afford isocyano intermediates 2-(2-isocyanatophenyl)quinolines. Followed by the nucleophilic addition with alcohol solvents, (2-(quinolin-2-yl)phenyl)carbamates were synthesized. This procedure features easy operation, a wide substrate scope, and mild conditions.

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Section: Introductionmentioning

confidence: 99%

Synthesis of (2-(Quinolin-2-yl)phenyl)carbamates by a One-Pot Friedel–Crafts Reaction/Oxidative Umpolung Aza-Grob Fragmentation Sequence

Xie

Long

et al. 2022

J. Org. Chem.

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“…Heterolytic fragmentation reactions (e.g., 2 → 3 ) can be useful strategic tools in organic synthesis. − When applied successfully, fragmentation reactions can effect ring expansion; , see, for example, the total synthesis of vinigrol . Examples in which fragmentation reactions have been useful continue to emerge in the literature (e.g., in bio-orthogonal self-immolative linkers), and we suspect that their utility will only continue to expand. Nevertheless, sparse mechanistic information hinders their broad use.…”

Section: Introductionmentioning

confidence: 99%

The Role of Through-Bond Stereoelectronic Effects in the Reactivity of 3-Azabicyclo[3.3.1]nonanes

2022

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Hyperconjugation/conjugation through-bond stereoelectronic effects were studied with density functional theory in the context of 3-azabicyclo[3.3.1]nonanes to unravel puzzling differences in reactivity between a vinylogous chloride (4) and a vinylogous ester (5). These compoundswhose structures differ only by one substituentwere found to display strikingly different reactivities in hydrochloric acid by Risch and co-workers (J. Am. Chem. Soc.199111394119412). Computational analyses of substituent effects, noncovalent interactions, natural bond orbitals, isodesmic reactions, and hydration propensities lead to a model for which the role of remote, through-bond stereoelectronic effects is the key to explaining 4 and 5’s diverging reactivity.

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Conjugated Polymers with Self‐Immolative Sidechain Linkers for Carbon Nanotube Dispersion

Yu,

Adronov

2024

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Single‐walled carbon nanotubes (SWNTs) are promising materials for generating high‐performance electronic devices. However, these applications are greatly restricted by their lack of purity and solubility. Commercially available SWNTs are a mixture of semi‐conducting (sc‐) and metallic (m‐) SWNTs and are insoluble in common solvents. Conjugated polymers can selectively disperse either sc‐ or m‐SWNTs and increase their solubility; however, the conductivity of conjugated polymer‐wrapped SWNTs is largely affected by the polymer side chains. Here, a poly(fluorene‐co‐phenylene) polymer that contains a self‐immolative linker as part of its sidechains is reported. The self‐immolative linker is stabilized with a tert‐butyldimethylsilyl ether group that, upon treatment with tetra‐n‐butylammonium fluoride (TBAF), undergoes a 1,6‐elimination reaction to release the sidechain. Sonication of this polymer with SWNTs in tetrahydrofuran (THF) results in concentrated dispersions that are used to prepare polymer‐SWNT thin films. Treatment with TBAF caused side‐chain cleavage into carbon dioxide and the corresponding diol, which can be easily removed by washing with solvent. This process is characterized by a combination of absorption and Raman spectroscopy, as well as four‐point probe measurements. The conductance of the SWNT thin films increased ≈60‐fold upon simple TBAF treatment, opening new possibilities for producing high‐conductivity SWNT materials for numerous applications.

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Bioorthogonal Self-Immolative Linker Based on Grob Fragmentation

Cited by 3 publications

References 25 publications

Synthesis of (2-(Quinolin-2-yl)phenyl)carbamates by a One-Pot Friedel–Crafts Reaction/Oxidative Umpolung Aza-Grob Fragmentation Sequence

Synthesis of (2-(Quinolin-2-yl)phenyl)carbamates by a One-Pot Friedel–Crafts Reaction/Oxidative Umpolung Aza-Grob Fragmentation Sequence

The Role of Through-Bond Stereoelectronic Effects in the Reactivity of 3-Azabicyclo[3.3.1]nonanes

Conjugated Polymers with Self‐Immolative Sidechain Linkers for Carbon Nanotube Dispersion

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