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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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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Iron-catalysed stereoselective NH transfer enables dynamic kinetic resolution of sulfoxides

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

Published: Feb. 8, 2025

Transition metal-catalysed asymmetric nitrene transfer provides a powerful means to access various bioactive N-containing compounds as single enantiomers. However, enantioselective NH that allows concise assembly of unprotected enantioenriched amines remains an enduring challenge. We report here iron-catalysed stereoselective imidation sulfoxide, which is integrated with photocatalytic racemisation enabling dynamic kinetic resolution (DKR) strategy for direct and synthesis NH-sulfoximines. This approach distinct from the existing methods by avoiding protecting group manipulations and/or use chiral substrates. Computational studies on reaction suggest involvement iron-aminyl radical intermediate, its sulfoxide proceeds through synchronous nucleophilic addition nitrogen center ligand-to-metal electron process form N–S bond. In addition, stereoselectivity primarily dictated difference in dispersion interactions transition states. Enantioselective Here, authors

Language: Английский

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

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 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.

Language: Английский

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Mechanochemical Enantiospecific Syntheses of Sulfonimidate Esters and Sulfonimidamides by Various S(VI) Exchange Reactions

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

Published: March 27, 2025

Mechanochemical S(VI) exchange reactions are developed on chiral S(VI)–F and S(VI)–Cl centers that fast, solvent–free, high–yielding, enantiospecific. This approach is used to synthesize a range of sulfonimidate esters sulfonimidamides from sulfonimidoyl fluorides chlorides under mild reaction conditions. The broad scope this method demonstrated by its successful reactivity with phenols both primary secondary anilines. Furthermore, substitution in 4–nitrophenol‐derived species substituted (SuPhenEx) successfully achieved. faster, greener, reduces the need for formation fluorinated species, while retaining many advantages SuFEx related reactions.

Language: Английский

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In Situ Generation and Reactivity of Fluorosulfonimidoyl Azide (R-N═SOFN₃): Expanding the Scope of SOF₄-Based SuFEx Chemistry

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Here, we report the use of iminosulfur oxydifluorides, derived from SOF4 and primary amines, for generation unprecedented aza-analogues fluorosulfury azide (FSO2N3), namely, fluorosulfonimidoyl (R-N═SOFN3). Unlike FSO2N3, R-N═SOFN3 acts as a sulfamoyl nitrene precursor, undergoing imidation with sulfoxides thioethers to products featuring unique "-N = S(VI)F-N S(VI)-" linkages without metal catalyst. The fluoride at S(VI) center can be sequentially exchanged generate diverse three-deminsional structures tunable SuFEx reactivity. Mechanistic studies reveal that R-N SOFN3 decomposes intermediate, which is stabilized by adjacent "-S(VI)=N-" nitrogen atom. This facilitates formation three-membered rings react further S(IV)/S(II). These novel transformations expand scope SOF4-based chemistry, demonstrating enables dual reactivity through both nitrene-driven SuFEx-based linkages.

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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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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