Dearomative ring expansion of thiophenes by bicyclobutane insertion

Science, Journal Year: 2023, Volume and Issue: 381(6653), P. 75 - 81

Published: July 6, 2023

Skeletal ring enlargement is gaining renewed interest in synthetic chemistry and has recently focused on insertion of one or two atoms. Strategies for heterocyclic expansion through small-ring remain elusive, although they would lead to the efficient formation bicyclic products. Here, we report a photoinduced dearomative thiophenes by bicyclo[1.1.0]butanes produce eight-membered rings under mild conditions. The value, broad functional-group compatibility, excellent chemo- regioselectivity were demonstrated scope evaluation product derivatization. Experimental computational studies point toward photoredox-induced radical pathway.

Language: Английский

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Skeletal Editing: Interconversion of Arenes and Heteroarenes

Helvetica Chimica Acta, Journal Year: 2023, Volume and Issue: 106(3)

Published: Jan. 13, 2023

Abstract Skeletal editing involves making specific point‐changes to the core of a molecule through selective insertion, deletion or exchange atoms. It thus represents potentially powerful strategy for step‐economic modification complex substrates and is perfect complement methods such as C−H functionalization that target molecular periphery. Given their ubiquity in biologically active compounds, ability perform skeletal on – therefore interconvert between aromatic heterocycles especially valuable. This review summarizes both recent key historical examples applied interconversion rings; we anticipate it will serve highlight not only innovative enabling nature current methods, but also tremendous opportunities still exist field.

Language: Английский

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Skeletal Editing of Pyrimidines to Pyrazoles by Formal Carbon Deletion

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(48), P. 22309 - 22315

Published: Nov. 28, 2022

A method for the conversion of pyrimidines into pyrazoles by a formal carbon deletion has been achieved guided computational analysis. The pyrimidine heterocycle is most common diazine in FDA-approved drugs, and are diazole. An efficient to convert would therefore be valuable leveraging chemistries unique access diversified pyrazoles. One known, though it proceeds low yields requires harsh conditions. transformation reported here under milder conditions, tolerates wide range functional groups, enables simultaneous regioselective introduction N-substitution on resulting pyrazole. Key success this one-carbon room-temperature triflylation core, followed hydrazine-mediated skeletal remodeling.

Language: Английский

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Carbon-to-nitrogen single-atom transmutation of azaarenes

Nature, Journal Year: 2023, Volume and Issue: 623(7985), P. 77 - 82

Published: Nov. 1, 2023

Language: Английский

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Cobalt-Catalyzed Nitrogen Atom Insertion in Arylcycloalkenes

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(49), P. 22433 - 22439

Published: Nov. 30, 2022

Developing strategies enabling the modification of underlying molecular frameworks facilitates access to underexplored chemical spaces. Skeletal editing is an emerging technology for late-stage diversification bioactive molecules. However, current state this knowledge remains undeveloped. This work describes a simple protocol that "inserts" nitrogen atom into arylcycloalkenes form corresponding N-heterocycles. The use inexpensive cobalt catalyst under aqueous and open-air conditions makes very practical. Examples compounds pharmaceutical interest complex fused ring further demonstrated potentially broad applicability methodology.

Language: Английский

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Nitrogen atom insertion into indenes to access isoquinolines

Chemical Science, Journal Year: 2023, Volume and Issue: 14(11), P. 2954 - 2959

Published: Jan. 1, 2023

We report a convenient protocol for nitrogen atom insertion into indenes to afford isoquinolines. The strategy further enables the synthesis of pyridines from cyclopentadienes and facile access 15 N labelled

Language: Английский

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Skeletal editing of pyridines through atom-pair swap from CN to CC

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(5), P. 741 - 748

Published: Jan. 18, 2024

Abstract Skeletal editing is a straightforward synthetic strategy for precise substitution or rearrangement of atoms in core ring structures complex molecules; it enables quick diversification compounds that not possible by applying peripheral strategies. Previously reported skeletal common arenes mainly relies on carbene- nitrene-type insertion reactions rearrangements. Although powerful, efficient and applicable to late-stage heteroarene structure modification, these strategies cannot be used pyridines. Here we report the direct pyridines through atom-pair swap from CN CC generate benzenes naphthalenes modular fashion. Specifically, use sequential dearomatization, cycloaddition rearomatizing retrocycloaddition one-pot sequence transform parent into bearing diversified substituents at specific sites, as defined reaction components. Applications pyridine cores several drugs are demonstrated.

Language: Английский

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‘Almost magical’: chemists can now move single atoms in and out of a molecule’s core

Nature, Journal Year: 2023, Volume and Issue: 618(7963), P. 21 - 24

Published: May 31, 2023

Language: Английский

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Carbon–Carbon Bond Cleavage for Late-Stage Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(22), P. 12313 - 12370

Published: Nov. 9, 2023

Late-stage functionalization (LSF) introduces functional group or structural modification at the final stage of synthesis natural products, drugs, and complex compounds. It is anticipated that late-stage would improve drug discovery's effectiveness efficiency hasten creation various chemical libraries. Consequently, products a productive technique to produce product derivatives, which significantly impacts biology development. Carbon-carbon bonds make up fundamental framework organic molecules. Compared with carbon-carbon bond construction, activation can directly enable molecular editing (deletion, insertion, atoms groups atoms) provide more efficient accurate synthetic strategy. However, selective unstrained still one most challenging projects in synthesis. This review encompasses strategies employed recent years for cleavage by explicitly focusing on their applicability functionalization. expands current discourse reactions providing comprehensive overview types bonds. includes C-C(sp), C-C(sp2), C-C(sp3) single bonds; double triple bonds, focus catalysis transition metals organocatalysts. Additionally, specific topics, such as ring-opening processes involving three-, four-, five-, six-membered rings, are discussed, exemplar applications these techniques showcased context bioactive molecules discovery. aims shed light advancements field propose potential avenues future research realm

Language: Английский

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Tunable molecular editing of indoles with fluoroalkyl carbenes

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(6), P. 988 - 997

Published: March 5, 2024

Language: Английский

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