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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The Catalytic Synthesis of Aza-Sulfur Functional Groups

Synthesis, Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Abstract Sulfur-containing compounds are found in myriad applications. Sulfones and sulfonamides the most common functional groups used medicinal agrochemical endeavours. Isosteres of these groups, for example, sulfoximines sulfonimidamides, emerging functionalities, they increasingly relevant patent literature. However, general, associated synthetic routes still have limitations, including use harsh reaction conditions highly reactive reagents. A variety catalytic reactions that employ a diverse range substrate classes been developed to address issues. This short review highlights recent syntheses aza-sulfur compounds, which we hope will open new directions discovery chemistry. 1 Introduction 2 Reactions N-Sulfinylamines 3 with Sulfenamides 4 Sulfinates 5 Sulfinamides 6 Other Aza-Sulfur Compounds 7 Conclusion

Язык: Английский

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Photoredox-catalyzed deoxygenative radical transformation of alcohols to sulfinamides

RSC Advances, Год журнала: 2025, Номер 15(6), С. 4532 - 4535

Опубликована: Янв. 1, 2025

Sulfinamides play a crucial role in organic synthesis and pharmaceuticals.

Язык: Английский

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Anionic Stereogenic-at-Cobalt(III) Complex-Enabled Asymmetric Oxidation of N,N-Dialkyl Sulfenamides

Organic Letters, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

An asymmetric oxidation of N,N-dialkyl sulfenamides is exhibited by using anionic stereogenic-at-cobalt(III) complexes as catalysts. This protocol provides an alternative approach to access a diverse set chiral tertiary sulfinamides with high enantioselectivities (24 examples, up 94:6 e.r.). Additionally, control experiments suggest that this could be accomplished through cationic S(IV) intermediate.

Язык: Английский

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Ruthenium-Catalyzed Enantioselective Alkylation of Sulfenamides: A General Approach for the Synthesis of Drug Relevant S-Methyl and S-Cyclopropyl Sulfoximines

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

Опубликована: Апрель 28, 2025

Sulfoximines are increasingly utilized in pharmaceuticals and agrochemicals with all sulfoximine clinical candidates incorporating either an S-methyl or S-cyclopropyl substituent. Here, we report on a general efficient sequence for the asymmetric synthesis of both these substitution patterns. The sulfilimine intermediates by first Ru-catalyzed enantioselective alkylation sulfenamides enables examples S-alkylation monosubstituted diazo compounds. reaction proceeds at ≤1 mol % Ru-catalyst loading, tert-butyl diazoacetate, high yields ≥98:2 er achieved exceedingly broad range sulfenamides, including S-(hetero)aryl, -alkenyl, -methyl, -benzyl, -branched alkyl, -tert-butyl substituents sterically electronically diverse N-acyl groups. Sulfenamides derived from densely functionalized advanced drug also alkylated 99:1 er. After oxidation N-pivaloyl S-tert-butyl acetate substituted to corresponding sulfoximine, treatment trifluoracetic acid aprotic solvent resulted decarboxylation while aqueous HCl cleavage group give NH sulfoximine. Alternatively, dibromoethane followed acid-mediated provided preclinical candidate LTGO-33 formal phase II ART0380 demonstrate utility disclosed approach.

Язык: Английский

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Asymmetric reductive arylation and alkenylation to access S-chirogenic sulfinamides

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

Опубликована: Март 15, 2025

The study of the stereochemistry organic sulfur compounds has been ongoing for over a century, with S-chirogenic pharmacophores playing an essential role in drug discovery within bioscience and medicinal chemistry. Traditionally, synthesis sulfinamides featuring stereogenic sulfur(IV) centers involves complex, multistep process that often depends on chiral auxiliaries or kinetic resolution. Here, we introduce effective versatile method synthesizing diverse classes through selective aryl alkenyl addition to sulfinylamines. This is catalysed by nickel cobalt complex under reductive conditions, eliminating need preformed organometallic reagents. facilitates incorporation array halides at position, enabling their integration into various biologically significant pharmacophores. Our detailed mechanistic investigations density functional theory calculations provide insights reaction pathway, particularly highlighting enantiocontrol mode during process. play authors report methodology asymmetric sulfinylamines via common-Earth-metal catalysis.

Язык: Английский

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Regioselective Synthesis of Thiazole‐5‐thione Based on [2 + 3] Annulation Trapping of α‐Keto Sulfine with Thioamide

European Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Окт. 22, 2024

Abstract Aiming to develop novel annulation reactions using sulfine intermediates, we have established a regioselective formal [2+3] cyclization reaction of α ‐keto sulfines generated from the elimination arylacyl sulfoxides and thioamides. This new strategy allows for synthesis thiazole‐5‐thiones directly without catalysts or additives. The approach features step‐economic, one‐pot characteristics via tandem sequence in situ generation, regiospecifically nucleophilic attack [3+2] cyclizatoin, dithioate (S=C−S−) skeletons formation, subsequent intramolecular cyclization. also represents method constructing skeletons.

Язык: Английский

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Construction of Sulfur(IV)‐Chiral Six‐Membered Heterocycles by Pd‐Catalyzed Asymmetric (4+2) Dipolar Cyclization

European Journal of Organic Chemistry, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 27, 2024

Abstract Chiral sulfur‐containing compounds play an important role in asymmetric catalysis and synthesis, chiral pharmaceuticals, materials. While great progress has been made the synthesis of these compounds, catalytic heterocycles remains relatively limited compared to acyclic ones. In this study, we successfully report efficient highly selective structurally diverse chirality‐at‐sulfur(IV) six‐membered under mild conditions via a Pd‐catalyzed (4+2) dipolar cyclization. More importantly, products enable enantioselective preparation variety other S‐stereogenic derivatives.

Язык: Английский

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Strategic Synthesis of Sulfinamides as Versatile S(IV) Intermediates

ACS Organic & Inorganic Au, Год журнала: 2024, Номер 5(1), С. 1 - 12

Опубликована: Ноя. 30, 2024

Sulfinamides constitute adaptable S(IV) intermediates with a sulfur stereocenter, having emerging interest in divergent synthesis of high-valent S(VI) functional bioisosteres. Recent years have witnessed the strategic development mild and selective synthetic routes for highly functionalized sulfinamides, employing stable organometallic reagents, carbon-centered radical precursors, other abundant coupling partners merged various reagents arena metal, photoredox, organocatalysis. Furthermore, asymmetric metal organocatalysis enabled stereoselective enantioenriched sulfinamides. In this Perspective, we present recent (2021 to present) advancement methods toward

Язык: Английский

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Theoretical study of Ni(0)-catalyzed intermolecular hydroamination of branched 1,3-dienes: reaction mechanism, regioselectivity, enantioselectivity, and prediction of the ligand

Journal of Molecular Modeling, Год журнала: 2024, Номер 31(1)

Опубликована: Дек. 11, 2024

Язык: Английский

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