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

Fen‐Ya Xiong,

Sudip Pan,

Bao‐Cheng Wang

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Unlocking Chiral Sulfinimidoyl Electrophiles: Asymmetric Synthesis of Sulfinamides Catalyzed by Anionic Stereogenic-at-Cobalt(III) Complexes DOI
Hua‐Jie Jiang, Fang Wei, Xinran Chen

et al.

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

Citations

4
Asymmetric reductive arylation and alkenylation to access S-chirogenic sulfinamides DOI Creative Commons

Xiaowu Fang,

Longlong Xi, Minyan Wang

et al.

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

Published: March 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.

Language: Английский

Citations

1
The Catalytic Synthesis of Aza-Sulfur Functional Groups DOI
Michael C. Willis,

Ming-Kai Wei

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

Citations

5
Photoredox-catalyzed deoxygenative radical transformation of alcohols to sulfinamides DOI Creative Commons
Xinyu Zhu, Junliang Wu, Junliang Zhang

et al.

RSC Advances, Journal Year: 2025, Volume and Issue: 15(6), P. 4532 - 4535

Published: Jan. 1, 2025

Sulfinamides play a crucial role in organic synthesis and pharmaceuticals.

Language: Английский

Citations

0
Anionic Stereogenic-at-Cobalt(III) Complex-Enabled Asymmetric Oxidation of N,N-Dialkyl Sulfenamides DOI

Yue Shen,

Xiaobao Wu,

Hua‐Jie Jiang

et al.

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

Citations

0
Ruthenium-Catalyzed Enantioselective Alkylation of Sulfenamides: A General Approach for the Synthesis of Drug Relevant S-Methyl and S-Cyclopropyl Sulfoximines DOI

Zachary W. Boyer,

Na Yeon Kwon, Jonathan A. Ellman

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 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.

Language: Английский

Citations

0
Reagent-Regulated Organocatalytic Enantiodivergent Synthesis of Chiral Sulfinimidate Esters DOI
Wei-Long Cui, Luoqiang Zhang,

Chu Liu

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: May 29, 2025

Achiral parameter-regulated enantiodivergent synthesis of chiral sulfur compounds has rarely been reported. Driven by the increasing importance aza-sulfur stereogenic centers in drug discovery, we present herein organocatalytic tandem enantioselective chlorination and nucleophilic substitution for sulfinimidate esters. The enantiopreference is modulated N-chlorophthalimide (NCP) trichloroisocyanuric acid (TCCA) with same enantiomer pentanidium catalyst, both enantiomers esters are obtained high enantiocontrol. Notably, reactions TCCA very fast completed 5 min, efficiency well maintained gram-scale synthesis. resulting versatile precursors diverse aza-S(IV) S(VI) centers. Studies on mechanism reveal that center inverted twice NCP, only a single inversion verified TCCA, representing novel strategy catalysis.

Language: Английский

Citations

0
Strategic Synthesis of Sulfinamides as Versatile S(IV) Intermediates DOI Creative Commons
Subham Das,

Amit Dhibar,

Basudev Sahoo

et al.

ACS Organic & Inorganic Au, Journal Year: 2024, Volume and Issue: 5(1), P. 1 - 12

Published: Nov. 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

Language: Английский

Citations

1
Construction of Sulfur(IV)‐Chiral Six‐Membered Heterocycles by Pd‐Catalyzed Asymmetric (4+2) Dipolar Cyclization DOI

Fen‐Ya Xiong,

Sudip Pan,

Bao‐Cheng Wang

et al.

European Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 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.

Language: Английский

Citations

0