Enantioselective Synthesis of Chiral Sulfonimidoyl Fluorides Facilitates Stereospecific SuFEx Click Chemistry DOI Open Access

He-sen Huang,

Yi Yuan, Wei Wang

et al.

Angewandte Chemie, 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

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

3
Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines DOI
Yixiang Shi,

Yin Yuan,

Jianhui Li

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(26), P. 17580 - 17586

Published: June 20, 2024

The application of sulfinamides has been witnessed in medicinal and agrochemistry with employment asymmetric transformations. However, methods for their catalytic synthesis have rarely explored. Herein, the enantioselective addition aryl boroxines to sulfinylamines via Cu catalyst newly developed Xuphos ligand were reported. A series chiral can be readily accessed one step. This protocol enables stereospecific transformation sulfonimidoyl fluorides, sulfonimidamides, sulfonimidate esters. DFT calculations revealed reaction pathway, migratory insertion is enantio-determining noncovalent interaction between oxygen atom C-H bonds crucial enantioselectivity control.

Language: Английский

Citations

10
Enantioselective S‐Alkylation of Sulfenamides by Phase‐Transfer Catalysis DOI Open Access
Andrew T. Champlin, Na Yeon Kwon, Jonathan A. Ellman

et al.

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

Published: July 26, 2024

Abstract A general phase‐transfer catalyst (PTC) mediated enantioselective alkylation of N ‐acylsulfenamides is reported. Essential to achieving high selectivity was the use triethylacetyl sulfenamide protecting group along with aqueous KOH as base under biphasic conditions enable reaction be performed at −40 °C. With these key parameters, enantiomeric ratios up 97.5 : 2.5 newly generated chiral sulfur center were achieved an inexpensive cinchona alkaloid derived PTC. Broad scope and excellent functional compatibility observed for a variety S ‐(hetero)aryl branched unbranched ‐alkyl sulfenamides. Moreover, achieve opposite enantiomer, pseudoenantiomeric designed synthesized from cinchonidine. Given that sulfoximines are bioactive pharmacophore ever‐increasing interest, selected product sulfilimines oxidized corresponding subsequent reductive cleavage affording free‐NH in yields. The utility disclosed method further demonstrated by efficient asymmetric synthesis atuveciclib, phase I clinical candidate which only HPLC separation had previously been reported isolation desired ( R )‐sulfoximine stereoisomer.

Language: Английский

Citations

8
Synthesis of chiral sulfilimines by organocatalytic enantioselective sulfur alkylation of sulfenamides DOI Creative Commons
Fucheng Wang, Weiming Xiang, Yiting Xie

et al.

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

Citations

6
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

4
Synthesis of P(V)-Stereogenic Phosphorus Compounds via Organocatalytic Asymmetric Condensation DOI

Fengrui Che,

Junyuan Hu,

Minghong Liao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

Enantioenriched phosphorus(V)-stereogenic compounds, featuring a pentavalent phosphorus atom as the stereogenic center, are crucial in various natural products, drugs, bioactive molecules, and catalysts/ligands. While handful of stereoselective synthetic approaches have been developed, achieving direct stereocontrol at through catalytic generation phosphorus(V)-heteroatom bonds continues to be formidable challenge. Here, we disclose an organocatalytic asymmetric condensation strategy that employs novel activation mode stable feedstock phosphinic acids by formation mixed anhydride reactive species facilitate further catalyst-controlled P-O bond formations, involving dynamic kinetic transformation (DYKAT) process with alcohol nucleophiles via cinchonidine-derived bifunctional catalyst. The resulting H-phosphinate intermediates allow stereospecific derivatizations, affording modular access diverse library chiral phosphonates phosphonamidates notable antibacterial activity. Furthermore, this platform facilitates P-O/N coupling products presenting valuable tool for medicine agrochemical discovery.

Language: Английский

Citations

4
Reductive sulfinylation by nucleophilic chain isomerization of sulfonylpyridinium DOI Creative Commons
Yifan Li, Weigang Zhang, Jeonguk Kweon

et al.

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

Published: Jan. 3, 2025

Language: Английский

Citations

0
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
Asymmetric S=N-embedded polyaromatic construction via enantioselective Pd-catalyzed C–H activation DOI Creative Commons

Daming Zeng,

Xinyu Zhang, Ming Wang

et al.

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

Published: March 28, 2025

Heteroatom-doped polyaromatic hydrocarbons show great potential for advancing photoelectric materials. SVI=N doping, characterized by soft-hard atom binding, donor-acceptor transmission, and chiroptical tuning, provides a powerful approach further optimizing the performance functionality of these However, introduction chiral sulfur(VI) has been formidable challenge due to intricate enantioselective discrimination embedded linkages with heteroatoms in systems. Herein, we establish an Pd-catalyzed desymmetrization diaryl sulfoximines sulfondiimines access SVI=N-doped heterocycles high yields enantioselectivities. The flexibility rigidity molecule distinct effect on enantioselectivity. split aromatic compounds exhibit C-H···π interactions involving additive TMCPA ligand S-aryl motif, producing (R)-configuration, while combined opposite (S)-configuration restricted bond rotation. photophysical study demonstrates carbazole-based heterocycle intense double absorption peaks favorable luminescence dissymmetry factor.

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