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

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(11), P. 6310 - 6318

Published: March 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.

Language: Английский

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Cu-Mediated Thianthrenation and Phenoxathiination of Arylborons

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(18), P. 10431 - 10440

Published: April 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.

Language: 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, Journal Year: 2023, Volume and Issue: 25(16), P. 2830 - 2834

Published: April 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.

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: 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, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 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.

Language: Английский

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

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 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

Language: Английский

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

Organic Letters, Journal Year: 2023, Volume and Issue: 25(18), P. 3179 - 3183

Published: April 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.

Language: Английский

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Synthesis of Sulfilimines via Aryne and Cyclohexyne Intermediates

Organic Letters, Journal Year: 2023, Volume and Issue: 25(27), P. 5157 - 5161

Published: July 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.

Language: Английский

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

Organic Letters, Journal Year: 2023, Volume and Issue: 25(25), P. 4759 - 4764

Published: June 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

Language: Английский

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Base-Promoted S-Arylation of Sulfenamides for the Synthesis of Sulfilimines

Organic Letters, Journal Year: 2023, Volume and Issue: 25(23), P. 4335 - 4339

Published: June 2, 2023

Sulfilimines are key intermediates to common motifs in medicines and agrochemicals. Typically, this class of compounds prepared by imidation thioethers, transition-metal-catalyzed or base-promoted sulfur alkylation arylation. Here, we report a practical efficient base-mediated arylation reaction for the preparation sulfilimines. A wide range N-acyl N-aryl sulfenamides react with various diaryliodonium salts smoothly afford sulfilimines high yields excellent chemoselectivities.

Language: Английский

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