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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Asymmetric 2,3-Addition of Sulfinylamines with Arylboronic Acids Enabled by Nickel Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17587 - 17594

Published: June 24, 2024

Sulfinamides have been widely used in organic synthesis, with research on their preparation spanning more than a century. Despite advancements catalytic methodologies, creating sulfur stereocenters within these molecules remains significant challenge. In this study, we present an effective and versatile method for synthesizing diverse range of S-chirogenic sulfinamides through asymmetric aryl addition to sulfinylamines. By utilizing nickel complex as catalyst, process exhibits impressive enantioselectivity can incorporate various arylboronic acids at the position. The resulting synthetic are stable highly adaptable, allowing conversion variety sulfur-containing compounds. Our study also incorporates detailed experimental computational studies elucidate reaction mechanism factors influencing enantioselectivity.

Language: Английский

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Synthesis of chiral sulfilimines by organocatalytic enantioselective sulfur alkylation of sulfenamides

Science Advances, Journal Year: 2024, Volume and Issue: 10(37)

Published: Sept. 13, 2024

Sulfilimines are versatile synthetic intermediates and important moieties in bioactive molecules. However, their applications drug discovery underexplored, efficient asymmetric methods highly desirable. Here, we report a transition metal–free pentanidium-catalyzed sulfur alkylation of sulfenamides with exclusive chemoselectivity over nitrogen high enantioselectivity. The reaction conditions were mild, wide range enantioenriched aryl alkyl sulfilimines obtained. utility practicability this robust protocol further demonstrated through gram-scale reactions late-stage functionalization drugs.

Language: Английский

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Catalyst Control over S(IV)-stereogenicity via Carbene-derived Sulfinyl Azolium Intermediates

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(36), P. 25350 - 25360

Published: Sept. 2, 2024

Stereoselective synthesis utilizing small-molecule catalysts, particularly N-heterocyclic carbene (NHC), has facilitated swift access to enantioenriched molecules through diverse activation modes and NHC-bound reactive intermediates. While carbonyl derivatives, imines, "activated" alkenes have been extensively investigated, the exploration of heteroatom-centered analogues intermediates long neglected, despite significant potential for novel chemical transformations they offer once recognized. Herein, we disclose a carbene-catalyzed new mode by generating unique sulfinyl azolium from nucleophilic addition in situ-generated mixed sulfinic anhydride Combined experimental computational mechanistic investigations pinpoint chiral NHC-catalyzed formation intermediate as enantio-determining step. The "S"-based imparts high efficiency catalytic construction sulfur-stereogenic compounds, giving rise sulfinate esters with yields enantioselectivities under mild conditions. Notably, distinct most enantioselective focusing on "C" central products, our study realizes carbene-catalyst control over "S" stereocenters via direct asymmetric S-O bond first time. Furthermore, these sulfinyl-containing products could serve versatile synthetic platforms

Language: Английский

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Electrochemical Conversions of Sulfenamides into Sulfonimidoyl- and Sulfondiimidoyl Fluorides

JACS Au, Journal Year: 2025, Volume and Issue: 5(5), P. 2359 - 2367

Published: April 29, 2025

The invention of versatile linkage agents provides the chemical basis for SuFEx chemistry. Sulfonimidoyl fluorides and sulfondiimidoyl are aza-isosteres sulfonyl with diverse reactivity through fine-tuning N-substituents. However, limited synthetic approaches impede their wide applications in Herein, we develop a straightforward electrochemical strategy sulfonimidoyl- sequential oxidations readily available sulfenamides via sulfinamide iminosulfinamide intermediates, respectively. previously rarely investigated (bis)-sulfondiimidoyl now easily accessible participate chemistry oxygen nitrogen nucleophiles, macrocyclization, polymerization.

Language: Английский

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The Catalytic Synthesis of Aza-Sulfur Functional Groups

Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 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

Language: Английский

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The Modular Synthesis of Sulfondiimidoyl Fluorides and their Application to Sulfondiimidamide and Sulfondiimine Synthesis

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(38)

Published: June 26, 2024

A modular synthesis of sulfondiimidoyl fluorides-the double aza-analogues sulfonyl fluorides-allowing variation the carbon and both nitrogen-substituents is reported. The chemistry uses readily available organometallic reagents, commercial sulfinylamines, simple electrophiles, N-fluorobenzenesulfonimide (NFSI), as starting materials. reactions are broad in scope, efficient, scalable. We show that fluoride products can be combined with amines to provide sulfondiimidamides, organolithium reagents sulfondiimines, reactivity these transformations modulated by N-substituents.

Language: Английский

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Computational analysis of modular diazotransfer reactions for the development of predictive reactivity models and diazotransfer reagents

Nature Synthesis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Language: Английский

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Enantioselective Synthesis of Chiral Sulfonimidoyl Fluorides Facilitates Stereospecific SuFEx Click Chemistry

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 5, 2024

Abstract Sulfur‐centered electrophilic ‘warheads’ have emerged as key components for chemical proteomic probes through sulfur‐exchange chemistry (SuFEx) with protein nucleophiles. Among these functional groups, sulfonimidoyl fluorides (SIFs) stand out their modifiable sites, tunable electrophilicities, and chiral sulfur‐center, presenting exciting possibilities new covalent probes. However, the synthetic access to SIFs has been a challenge, limiting exploration applications. In this study, we describe convenient route obtain from readily available sulfenamides via series of one‐pot tandem reactions high enantiomeric excess (ees). The resulting were further converted into diverse array S(VI) derivatives under mild conditions or in buffer solutions. Most significantly, specificity ligation experiments underscored critical role sulfur‐center chirality design screening more‐selective therapeutics.

Language: Английский

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Poison to promise: The resurgence of organophosphorus fluoride chemistry

Chem, Journal Year: 2024, Volume and Issue: 10(6), P. 1644 - 1654

Published: May 9, 2024

Language: Английский

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