Late-stage difluoromethylation: concepts, developments and perspective

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(14), P. 8214 - 8247

Published: Jan. 1, 2021

This review describes the conceptual advances that have led to multiple difluoromethylation processes making use of well-defined CF₂H sources.

Language: Английский

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Selective Decarbonylation via Transition-Metal-Catalyzed Carbon–Carbon Bond Cleavage

Chemical Reviews, Journal Year: 2020, Volume and Issue: 121(1), P. 365 - 411

Published: June 16, 2020

Transition-metal-catalyzed decarbonylation via carbon–carbon bond cleavage is an essential synthetic methodology. Given the ubiquity of carbonyl compounds, selective decarbonylative process offers a distinct strategy using groups as "traceless handles". This reaction has been significantly developed in recent years many respects, including catalytic system development, mechanistic understanding, substrate scope, and application synthesis complex functional molecules. Therefore, this review aims to summarize progress on transition-metal-catalyzed process, from discovery new transformations understanding mechanisms, reveal great achievements potentials field. The contents are categorized by type chemical process. main challenges opportunities also examined with goal expanding range reactions.

Language: Английский

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Contemporary synthetic strategies in organofluorine chemistry

Nature Reviews Methods Primers, Journal Year: 2021, Volume and Issue: 1(1)

Published: July 8, 2021

Language: Английский

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Direct C–H difluoromethylation of heterocycles via organic photoredox catalysis

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Jan. 31, 2020

Abstract The discovery of modern medicine relies on the sustainable development synthetic methodologies to meet needs associated with drug molecular design. Heterocycles containing difluoromethyl groups are an emerging but scarcely investigated class organofluoro molecules potential applications in pharmaceutical, agricultural and material science. Herein, we developed organophotocatalytic direct difluoromethylation heterocycles using O 2 as a green oxidant. C–H oxidative obviates need for pre-functionalization substrates, metals additives. operationally straightforward method enriches efficient synthesis many difluoromethylated moderate excellent yields. pharmaceutical moleculars demonstrates practicability this methodology late-stage development. Moreover, 2′-deoxy-5-difluoromethyluridine (F TDR) exhibits promising activity against some cancer cell lines, indicating that might provide assistance discovery.

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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Silver‐Catalyzed Decarboxylative Allylation of Difluoroarylacetic Acids with Allyl Sulfones in Water

Chemistry - An Asian Journal, Journal Year: 2020, Volume and Issue: 15(7), P. 1175 - 1179

Published: Feb. 14, 2020

A practical silver-catalyzed decarboxylative allylation of α,α-difluoroarylacetic acids with allyl sulfones is described, which provides a variety β,β-difluorinated alkenes in good yields. Notably, the reaction proceeds smoothly water functional group tolerance. The practicality and synthetic value this process was demonstrated by scaled-up experiment elaboration products via reduction or Heck reaction. Primary mechanism investigations suggest that radical might be involved.

Language: Английский

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Modern approaches towards the synthesis of geminal difluoroalkyl groups

Organic & Biomolecular Chemistry, Journal Year: 2021, Volume and Issue: 19(5), P. 947 - 964

Published: Jan. 1, 2021

This review will cover the importance of and most recent approaches toward geminal difluoroalkyl groups using transition metal-mediated, photochemical, organocatalytic, other methods.

Language: Английский

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State of knowledge in photoredox-catalysed direct difluoromethylation

Organic Chemistry Frontiers, Journal Year: 2022, Volume and Issue: 9(13), P. 3598 - 3623

Published: Jan. 1, 2022

The combination of visible light photoredox catalysis with direct difluoromethylation has allowed the synthesis a large choice CF 2 H-containing value-added molecules under very mild reaction conditions.

Language: Английский

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Highly Regio‐ and Enantioselective Hydrosilylation of gem‐Difluoroalkenes by Nickel Catalysis

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(10)

Published: Dec. 27, 2021

The synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation stereocenters through Ni0 -catalyzed regio- and enantioselective hydrosilylation gem-difluoroalkenes. reaction also represents construction carbon(sp3 )-silicon bonds nickel catalysis, which provides atom- step-economical route high-value optically active α-difluoromethylsilanes. This protocol features readily available starting materials commercial chiral broad substrates spanning range functional groups high yield (up to 99 % yield) excellent enantioselectivity 96 ee). enantioenriched products undergo variety stereospecific transformations. Preliminary mechanistic studies were performed.

Language: Английский

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Divergent Acyl and Decarbonylative Liebeskind–Srogl Cross-Coupling of Thioesters by Cu-Cofactor and Pd–NHC (NHC = N-Heterocyclic Carbene) Catalysis

ACS Catalysis, Journal Year: 2023, Volume and Issue: 13(3), P. 1848 - 1855

Published: Jan. 17, 2023

Transition-metal-catalyzed cross-coupling reactions of thioesters by selective acyl C(O)–S cleavage have emerged as a powerful platform for the preparation complex molecules. Herein, we report divergent Liebeskind–Srogl Pd–NHC (NHC = N-heterocyclic carbene) catalysis. The reaction provides straightforward access to functionalized ketones highly C(acyl)–S under mild conditions. Most crucially, conditions enable direct functionalization range pharmaceuticals decorated with palette sensitive functional groups, providing attractive products medicinal chemistry programs. Furthermore, decarbonylative C(acyl)–S/C(aryl)–C(O) is reported. Cu metal cofactor directs pathway an or pathway. This reactivity applicable pharmaceuticals. represents mildest Suzuki discovered date. Cu-directed and opens up chemical space in molecule synthesis.

Language: Английский

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