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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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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Enantioselective sulfinylation of alcohols and amines by condensation with sulfinates

Chem, Год журнала: 2024, Номер 10(5), С. 1541 - 1552

Опубликована: Март 15, 2024

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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Assembly of (hetero)aryl sulfilimines via copper-catalyzed enantioselective S-arylation of sulfenamides with (hetero)aryl Iodides

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 8, 2025

The (hetero)aryl sulfoximines are important structures for developing bioactive molecules, whose synthesis relies on oxidation of sulfilimines. However, asymmetric approaches assembling sulfilimines still rare. Here we show that combination CuI and NOBIN-derived amide ligands offers an effective catalytic system enantioselective coupling iodides with sulfenamides. A large number functional groups heterocycles tolerated under the conditions, providing a powerful approach diverse enantioenriched efficiency reaction is highly dependent electronic nature Both (hetero)aryl- some bulky alkyl-substituted sulfenamides give excellent enantioselectivities, while smaller alkyl substituents lead to formation moderate enantioselectivities. Density theory (DFT) calculations reveal proper steric repulsions in transition states intramolecular SNAr crucial achieving desirable enantioselectivity. (Hetero)aryl useful bioisosteres sulfones medicinal chemistry as they have improved aqueous solubility metabolic stability. Here, authors report via copper-catalysed

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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Asymmetric Synthesis of Chiral Sulfimides through the O‐Alkylation of Enantioenriched Sulfinamides and Addition of Carbon Nucleophiles

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(16)

Опубликована: Фев. 21, 2023

Chiral sulfimides, the aza-analogues of sulfoxides, are valuable compounds in organic synthesis and medicinal chemistry. Herein, we report an efficient method for preparing chiral sulfimides from easily available enantioenriched sulfinamides. The key step this is a stereospecific oxygen-selective alkylation sulfinamides, which accomplished by using isopropyl iodide, K2 CO3 , DMPU. resulting sulfinimidate esters transformed to nucleophilic addition Grignard reagents under simple conditions. This transformation enables access diaryl or dialkyl bearing two similar carbon substituents, difficult synthesize previous methods.

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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