Synthesis of Sulfilimines Enabled by Copper-Catalyzed S-Arylation of Sulfenamides

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(11), С. 6310 - 6318

Опубликована: Март 9, 2023

Herein, an unprecedented synthetic route to sulfilimines via a copper-catalyzed Chan–Lam-type coupling of sulfenamides is presented. A key success in this novel transformation the chemoselective S-arylation S(II) form S(IV) sulfilimines, overriding competitive, and more thermodynamically favored, C–N bond formation that does not require change sulfur oxidation state. Computations reveal selectivity arises from selective transmetallation event where bidentate sulfenamide coordination through oxygen atoms favors pathway. The mild environmentally benign catalytic conditions enable broad functional group compatibility, allowing variety diaryl or alkyl aryl be efficiently prepared. Chan–Lam procedure could also tolerate alkenylboronic acids as partners afford alkenyl class scaffolds cannot directly synthesized conventional imination strategies. benzoyl-protecting groups conveniently removed product, which, turn, readily transformed into several S(VI) derivatives.

Язык: Английский

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Cu-Mediated Thianthrenation and Phenoxathiination of Arylborons

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(18), С. 10431 - 10440

Опубликована: Апрель 26, 2023

Great success in synthetic chemistry is motivated by the development of novel and reactive linchpins for carbon-carbon carbon-heteroatom bond formation reactions, which has dramatically altered chemists' approach to building molecules. Herein, we report ready synthesis aryl sulfonium salts, a versatile electrophilic linchpin, via Cu-mediated thianthrenation phenoxathiination commercially available arylborons with thianthrene phenoxathiine, providing series salts high efficiency. More importantly, leveraging sequential Ir-catalyzed C-H borylation arylborons, formal arenes also achieved. The undirected normally occurred at less steric hindrance position, thus complementary method comparison thianthrenation. This process capable late-stage functionalization pharmaceuticals, might find wide applications both industry academic sectors.

Язык: Английский

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Sulfur-Arylation of Sulfenamides via Chan–Lam Coupling with Boronic Acids: Access to High Oxidation State Sulfur Pharmacophores

Organic Letters, Год журнала: 2023, Номер 25(16), С. 2830 - 2834

Опубликована: Апрель 12, 2023

Sulfur-arylation of sulfenamides is reported. This reaction proceeds via a Chan-Lam-type coupling with commercially abundant boronic acids to give sulfilimines. A broad scope was established variety readily accessible aryl and alkyl sulfenamide acid inputs. Synthetic utility functional group compatibility were further demonstrated through the direct late-stage introduction sulfilimines into approved drugs. Derivatization sulfilimine products provided access medicinally relevant sulfoximines sulfondiimines.

Язык: Английский

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Unlocking Chiral Sulfinimidoyl Electrophiles: Asymmetric Synthesis of Sulfinamides Catalyzed by Anionic Stereogenic-at-Cobalt(III) Complexes

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 2, 2025

Asymmetric catalysis involving a sulfoxide electrophile intermediate presents an efficient methodology for accessing stereogenic-at-sulfur compounds, such as sulfinate esters, sulfinamides, etc., which have garnered increasing attention in modern pharmaceutical sciences. However, the aza-analog of electrophiles, asymmetric issues about electrophilic sulfinimidoyl species remain largely unexplored and represent significant challenge sulfur stereochemistry. Herein, we exhibit anionic stereogenic-at-cobalt(III) complex-catalyzed synthesis chiral sulfinamides via iodide intermediates. Mechanistic investigations reveal that catalytic cycle is initiated by oxidative iodination, generating iodides. These active intermediates subsequently undergo enantiospecific nucleophilic substitution with water, affording diverse array enantioenriched sulfinamides. Notably, these promising antifungal activities against Sclerotinia sclerotiorum serve ideal platform molecules facilitating stereospecific transformation into various stereogenic aza-sulfur compounds.

Язык: Английский

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Sulfilimines from a Medicinal Chemist’s Perspective: Physicochemical and in Vitro Parameters Relevant for Drug Discovery

Journal of Medicinal Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

While sulfoximines are nowadays a well established functional group for medicinal chemistry, the properties of sulfilimines significantly less studied, and no sulfilimine has progressed to clinic date. In this account, physicochemical in vitro reported compared those other more traditional groups. Furthermore, impact on real drug scaffolds is studied two series sulfilimine-containing analogs imatinib hNE inhibitors. We show that can be chemically configurationally stable under physiologically relevant conditions they basic highly polar thus often beneficial solubility metabolic stability, although at cost reduced permeability. conclude S-cyclopropyl,S-(hetero)aryl S,S-di(hetero)aryl so far neglected but potentially valuable S(IV) based pharmacophores deserve considered as part chemistry toolbox.

Язык: Английский

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Redox-Neutral Strategy for Sulfilimines Synthesis via S-Arylation of Sulfenamides

Organic Letters, Год журнала: 2023, Номер 25(18), С. 3179 - 3183

Опубликована: Апрель 27, 2023

In this investigation, an unprecedented transition-metal-free and redox-neutral synthesis of sulfilimines was realized through the S-arylation readily obtainable sulfenamides employing diaryliodonium salts. The pivotal step encompassed resonance between bivalent nitrogen-centered anions, engendered postdeprotonation under alkaline conditions, sulfinimidoyl anions. experimental outcomes demonstrate that anionic species function as efficacious nucleophilic reagents, affording with notable to exceptional yields superlative chemoselectivity, all executed within a protocol exceptionally mild conditions.

Язык: Английский

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Synthesis of Sulfilimines via Aryne and Cyclohexyne Intermediates

Organic Letters, Год журнала: 2023, Номер 25(27), С. 5157 - 5161

Опубликована: Июль 5, 2023

An efficient and metal-free approach for the synthesis of sulfilimines from sulfenamides with aryne cyclohexyne precursors has been developed. The reaction proceeds through unusual S–C bond formation, which offers a novel practical entry to access wide range in moderate good yields excellent chemoselectivity. Moreover, this protocol is amenable gram-scale applicable transformation products into useful sulfoximines.

Язык: Английский

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Sulfur-Arylation of Sulfenamides via Ullmann-Type Coupling with (Hetero)aryl Iodides

Organic Letters, Год журнала: 2023, Номер 25(25), С. 4759 - 4764

Опубликована: Июнь 20, 2023

Sulfur-(hetero)arylation of sulfenamides with commercially abundant (hetero)aryl iodides by Ullmann-type coupling inexpensive copper(I) iodide as the catalyst is reported. A broad scope reaction inputs was demonstrated, including both aryl and alkyl highly sterically hindered 5- 6-membered ring heteroaryl iodides. Relevant to many bioactive high oxidation state sulfur compounds, (hetero)arylation

Язык: Английский

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Preparation of Sulfilimines by Sulfur-Alkylation of N-Acyl Sulfenamides with Alkyl Halides

The Journal of Organic Chemistry, Год журнала: 2023, Номер 88(11), С. 7607 - 7614

Опубликована: Май 24, 2023

Sulfur alkylation of N-acyl sulfenamides with alkyl halides provides sulfilimines in 47% to 98% yields. A broad scope was established a variety aryl and sulfenamides, including for different groups. Alkyl steric electronic properties were effective inputs, methyl, primary, secondary, benzyl, propargyl halides. proof-of-concept asymmetric phase-transfer also demonstrated. sulfilimine product readily converted an free sulfoximine, which represent important motifs medicinal chemistry.

Язык: Английский

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Redox-Neutral Synthesis of Sulfilimines through the S-Alkylation of Sulfenamides

Organic Letters, Год журнала: 2023, Номер 25(18), С. 3173 - 3178

Опубликована: Апрель 27, 2023

In this work, we developed a metal-free and redox-neutral strategy for the selective S-alkylation of sulfenamides under basic conditions to yield sulfilimines. The key step involves resonance between bivalent nitrogen-centered anions, generated after deprotonation alkaline conditions, sulfinimidoyl anions. Our sustainable efficient approach employs sulfur-selective alkylation readily accessible commercially available halogenated hydrocarbons, resulting in successful synthesis 60 sulfilimines high yields (36-99%) short reaction times.

Язык: Английский

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