Cyclic Alkenylsulfonyl Fluorides: Palladium‐Catalyzed Synthesis and Functionalization of Compact Multifunctional Reagents

Angewandte Chemie International Edition, Journal Year: 2019, Volume and Issue: 58(52), P. 18859 - 18863

Published: Oct. 15, 2019

A series of low-molecular-weight, compact, and multifunctional cyclic alkenylsulfonyl fluorides were efficiently prepared from the corresponding alkenyl triflates. Palladium-catalyzed sulfur dioxide insertion using surrogate reagent DABSO effects sulfinate formation, before trapping with an F electrophile delivers sulfonyl fluorides. broad range functional groups are tolerated, a correspondingly large collection derivatization reactions possible on products, including substitution at sulfur, conjugate addition, N-functionalization. Together, these attributes suggest that this method could find new applications in chemical biology.

Language: Английский

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Copper-free Sandmeyer-type Reaction for the Synthesis of Sulfonyl Fluorides

Organic Letters, Journal Year: 2020, Volume and Issue: 22(8), P. 3072 - 3078

Published: March 31, 2020

A copper-free Sandmeyer-type fluorosulfonylation reaction is reported. Utilizing Na2S2O5 and Selectfluor as the sulfur dioxide fluorine sources, respectively, aryldiazonium salts were transformed into sulfonyl fluorides. The one-pot direct synthesis of fluorides from aromatic amines was also realized via in situ diazotization. practicality this method demonstrated by broad functional group tolerance, gram-scale synthesis, late-stage natural products pharmaceuticals.

Language: Английский

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Discovery of Lysine-Targeted eIF4E Inhibitors through Covalent Docking

Journal of the American Chemical Society, Journal Year: 2020, Volume and Issue: 142(11), P. 4960 - 4964

Published: Feb. 27, 2020

Eukaryotic translation initiation factor 4E (eIF4E) binds the m7GTP cap structure at 5'-end of mRNAs, stimulating proteins implicated in cancer cell growth and metastasis. eIF4E is a notoriously challenging target, most reported inhibitors are negatively charged guanine analogues with negligible permeability. To overcome these challenges, we envisioned covalent targeting strategy. As there no cysteines near binding site, developed docking approach focused on lysine. Taking advantage "make-on-demand" virtual library, used to identify arylsulfonyl fluorides that target noncatalytic lysine (Lys162) eIF4E. Guided by cocrystal structures, elaborated fluoride 2 12, which our knowledge first inhibitor cellular activity. In addition providing new tool for acutely inactivating cells, computational may offer general strategy developing selective lysine-targeted ligands.

Language: Английский

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A Unified Strategy for Arylsulfur(VI) Fluorides from Aryl Halides: Access to Ar‐SOF₃ Compounds

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(52), P. 23510 - 23515

Published: Sept. 17, 2020

A convenient protocol to selectively access various arylsulfur(VI) fluorides from commercially available aryl halides in a divergent fashion is presented. Firstly, novel sulfenylation reaction with the electrophilic N-(chlorothio)phthalimide (Cl-S-Phth) and arylzinc reagents afforded corresponding Ar-S-Phth compounds. Subsequently, S(II) atom was oxidized distinct fluorinated sulfur(VI) compounds under mild conditions. Slight modifications on oxidation permit chemoselective installation of 1, 3, or 4 fluorine atoms at S(VI) center, affording Ar-SO2 F, Ar-SOF3 , Ar-SF4 Cl. Of notice, this strategy enables effective introduction rare underexplored -SOF3 moiety into (hetero)aryl groups. Reactivity studies demonstrate that such elusive can be utilized as linchpin for synthesis highly coveted sulfonimidoyl (Ar-SO(NR)F).

Language: Английский

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Introducing A New Class of Sulfonyl Fluoride Hubs via Radical Chloro‐Fluorosulfonylation of Alkynes

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 60(40), P. 22035 - 22042

Published: Aug. 12, 2021

Sulfonyl fluorides have widespread applications in many important fields, including ligation chemistry, chemical biology, and drug discovery. Therefore, new methods to increase the synthetic efficiency expand available structures of sulfonyl are highly demand. Here, we introduce a powerful class fluoride hubs, β-chloro alkenylsulfonyl (BCASF), which can be constructed via radical chloro-fluorosulfonyl difunctionalization alkynes under photoredox conditions. BCASF molecules exhibit versatile reactivities well undergo series transformations at chloride site while keeping group intact, reduction, Suzuki coupling, Sonogashira as nucleophilic substitution with various nitrogen, oxygen, sulfur nucleophiles. By using hub, wide range becomes readily accessible, such cis fluorides, dienylsulfonyl ynenylsulfonyl challenging or even not possible synthesize before known methods. Moreover, further application late-stage modification peptides drugs is also demonstrated.

Language: Английский

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