Three-Component Sulfonylation and Heteroannulation Enabled by 3-Fold Defluorofunctionalization of Trifluoromethyl Enones

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 23, 2025

Trifluoromethyl enone emerges as a versatile and multifaceted building block in organic synthesis. A defluorinative heterocyclization reaction of readily available β,β-ditrifluoromethylated enones biocompatible sodium sulfinates has been developed for the modular synthesis densely functionalized furans with regio-defined C2,4-bissulfonyl C3-trifluoromethyl substitutions. This three-component method proceeds through sequential sulfonylation intramolecular O-cyclization, enabling assembly one furan ring, formation C-SO2/C–O bonds, cleavage three C(sp3)-F bonds one-pot manner under transition metal-free conditions. Moreover, obtained product can further react benzyne precursor to generate 1,4-epoxynaphthalene Diels–Alder cycloaddition. The is also distinguished by its broad substrate scope, excellent functional group tolerance, scalability.

Language: Английский

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Perfluoroalkyl Editing of Fluoroalkynes: Chemo-, Regio-, and Stereoselective Synthesis of (E)-(2-Amino-fluoroalkenyl)pyrimidines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

A chemo-, regio-, and stereoselective condensation reaction of perfluoroalkyl alkynes (PFAAs), (CH2O)n, (NH4)2CO3 through the cleavage five inert C(sp3)-F bonds at three distinct carbon sites, thereby establishing an unprecedented platform for synthesizing structurally unique (E)-(2-amino-fluoroalkenyl)pyrimidines, is first developed. Remarkably, this features mild conditions, good compatibility with various functional groups, excellent E-stereoselectivity, late-stage modification complex molecules, scalability, versatile synthetic transformations resulting heterocyclic compounds.

Language: Английский

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[4+2] Defluorocycloaddition of Perfluoroalkyl Alkynes and Benzylamines: Synthesis of meta-Fluoroalkylated Pyridin-4-amines

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 28, 2025

Pyridines represent privileged heterocycles, and the ability to produce fluorinated pyridines from polyfluorinated substances through selective defluorofunctionalization is a new addition their synthesis. Herein, an unprecedented formal [4+2] defluorocycloaddition of perfluoroalkyl alkynes benzylamines under metal-free conditions described. By leveraging functionalization four C(sp3)–F bonds on two vicinal sterically hindered carbons alkynes, diverse array meta-fluoroalkylated pyridin-4-amines were synthesized with good functional group tolerance. The mechanistic studies revealed sequence hydroamination, successive defluorination, 6π-electrocyclization, aromatization, amination.

Language: Английский

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Water-Involved 1,3-Aminoxylation of Fluoroalkenes: Chemo-, Regio-, and Stereoselective Synthesis of β-Fluoroacyl Vinylamines

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Perfluoroalkyl alkenyl iodides (PFAIs) are emerging as highly reactive, storage-stable, and multifunctional fluoroalkyl-bearing reagents, facilitating the manufacture of value-added organofluorides through multi-halo-functionalization. Herein, we developed a water-involved 1,3-aminoxylation PFAIs with sulfonamides for chemo-, regio-, Z-stereoselective synthesis valuable β-fluoroacyl vinylamines. This reaction proceeded via sequential deiodoamination defluoroxylation process under transition-metal-free conditions, featuring broad substrate scope good functional group tolerance. Compared to reported methods, some drawbacks, such multistep manipulation, harsh need expensive catalysts, use toxic/sensitive could be eliminated. Furthermore, synthetic potential this method was demonstrated scale-up synthesis, postfunctionalization complex molecules, ready transformation products.

Language: Английский

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Diastereoselective Formal [3+3] Cascade Cyclization towards Fused 4‐Fluoroalkylated 3,4‐Dihydro‐2H‐pyrans via Copper Catalysis

Chinese Journal of Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 25, 2025

Comprehensive Summary The cycloaddition and annulation reactions offer a powerful method toward various important substituted 3,4‐dihydro‐2 H ‐pyran architectures. Nevertheless, the transformation for preparing fused‐polycyclic ones still remains challenging yet highly desirable until now. Herein, we report novel formal [3+3] cascade cyclization reaction to provide lactam‐fused 4‐fluoroalkylated 3,4‐dihydropyran skeletons bearing three contiguous tertiary carbon centers via copper catalysis. Of note, these annulations proceeded in an exclusively diastereoselective manner through successive inert C(sp 2 )‐Cl 3 )‐H functionalization, which exhibited site‐selectivity stereoselectivity. Additionally, evaluations on biological activities of obtained products revealed that several display inhibitory activity against Siha H1975 cancer cell lines.

Language: Английский

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