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

---

Catalytic Asymmetric Synthesis of Sulfinamides via Cu-Catalyzed Asymmetric Addition of Aryl Boroxines to Sulfinylamines

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(26), С. 17580 - 17586

Опубликована: Июнь 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.

Язык: Английский

---

Enantioselective S‐Alkylation of Sulfenamides by Phase‐Transfer Catalysis

Angewandte Chemie International Edition, Год журнала: 2024, Номер unknown

Опубликована: Июль 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.

Язык: Английский

---

Synthesis of chiral sulfilimines by organocatalytic enantioselective sulfur alkylation of sulfenamides

Science Advances, Год журнала: 2024, Номер 10(37)

Опубликована: Сен. 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.

Язык: Английский

---

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

---

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

Journal of the American Chemical Society, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 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.

Язык: Английский

---

Reductive sulfinylation by nucleophilic chain isomerization of sulfonylpyridinium

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

Опубликована: Янв. 3, 2025

Язык: Английский

---

Synthesis of Chiral N-Free Sulfinamides by Asymmetric Condensation of Stable Sulfinates and Ammonium Salts

Chemical Communications, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

An organocatalytic approach using stable, cost-effective ammonium salts for asymmetric sulfinylation, achieving a broad range of enantioenriched sulfinamides was disclosed.

Язык: Английский

---

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

---

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

---