Assembly of (hetero)aryl sulfilimines via copper-catalyzed enantioselective S-arylation of sulfenamides with (hetero)aryl Iodides DOI Creative Commons
Mingchuang He,

Rongxing Zhang,

Tongkun Wang

et al.

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

Published: March 8, 2025

The (hetero)aryl sulfoximines are important structures for developing bioactive molecules, whose synthesis relies on oxidation of sulfilimines. However, asymmetric approaches assembling sulfilimines still rare. Here we show that combination CuI and NOBIN-derived amide ligands offers an effective catalytic system enantioselective coupling iodides with sulfenamides. A large number functional groups heterocycles tolerated under the conditions, providing a powerful approach diverse enantioenriched efficiency reaction is highly dependent electronic nature Both (hetero)aryl- some bulky alkyl-substituted sulfenamides give excellent enantioselectivities, while smaller alkyl substituents lead to formation moderate enantioselectivities. Density theory (DFT) calculations reveal proper steric repulsions in transition states intramolecular SNAr crucial achieving desirable enantioselectivity. (Hetero)aryl useful bioisosteres sulfones medicinal chemistry as they have improved aqueous solubility metabolic stability. Here, authors report via copper-catalysed

Language: Английский

Organocatalytic skeletal reorganization for enantioselective synthesis of S-stereogenic sulfinamides DOI Creative Commons

Zanjiao Liu,

Siqiang Fang,

Haoze Li

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 22, 2024

Abstract The enantioselective synthesis of S -stereogenic sulfinamides has garnered considerable attention due to their structural and physicochemical properties. However, catalytic asymmetric still remains daunting challenges, impeding broad application in drug discovery development. Here, we present an approach for the through peptide-mimic phosphonium salt-catalyzed skeletal reorganization simple prochiral and/or racemic sulfoximines. This methodology allows facile access a diverse array substituted with excellent enantioselectivities, accommodating various substituent patterns desymmetrization or parallel kinetic resolution process. Mechanistic experiments, coupled density functional theory calculations, clarify stepwise pathway involving ring-opening ring-closing processes, step identified as crucial achieving stereoselective control. Given prevalence centers pharmaceuticals, anticipate that this protocol will enhance efficient precise relevant chiral molecules analogs, thereby contributing advancements discovery.

Language: Английский

Citations

7
A combined experimental and computational study of ligand-controlled Chan-Lam coupling of sulfenamides DOI Creative Commons

Kaiming Han,

Hong Liu, Madeline E. Rotella

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 4, 2024

Abstract The unique features of the sulfenamides’ S(II)-N bond lead to interesting stereochemical properties and significant industrial functions. Here we present a chemoselective Chan–Lam coupling sulfenamides prepare N -arylated sulfenamides. A tridentate pybox ligand governs chemoselectivity favoring C–N formation, overrides competitive C-S formation by preventing S,N-bis-chelation copper center. Cu(II)-derived resting state catalyst is captured UV-Vis spectra EPR technique, key intermediate confirmed isotope response using 15 N-labeled sulfenamide. computational mechanistic study reveals that -arylation both kinetically thermodynamically favorable, with deprotonation sulfenamide nitrogen atom occurring prior reductive elimination. origin ligand-controlled explored, interaction between substrate controlling energy S corresponding product distribution, in agreement studies kinetic results.

Language: Английский

Citations

6
Synthesis of Sulfoximines by Copper-Catalyzed Oxidative Coupling of Sulfinamides and Aryl Boronic Acids DOI
Xi Zou, Hanbing Wang, Bing Gao

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(42), P. 7656 - 7660

Published: Oct. 12, 2023

A novel copper-catalyzed cross-coupling reaction of sulfinamides and aryl boronic acids is developed. The highly chemoselective stereospecific, which allows mild synthesis optically pure sulfoximines with broad scope functional group tolerance. utility this method demonstrated by the asymmetric pharmaceutical intermediates.

Language: Английский

Citations

16
Chiral Phosphoric Acid Catalyzed Asymmetric Hydrolysis of Biaryl Oxazepines for the Synthesis of Axially Chiral Biaryl Amino Phenol Derivatives DOI

Liwen Wei,

Jiaomeng Li, Yi Zhao

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(39)

Published: June 20, 2023

The development of catalytic asymmetric reaction with water as the reactant is challenging due to reactivity- and stereoselectivity-control issues resulted from low nucleophilicity small size water. We disclose herein a chiral phosphoric acid (CPA) catalyzed atroposelective ring-opening biaryl oxazepines A series undergo CPA hydrolysis in highly enantioselective manner. key for success this use new SPINOL-derived catalyst high reactivity oxazepine substrates towards under acidic conditions. Density functional theory calculations suggest that proceeds via dynamic kinetic resolution pathway addition imine group both enantio- rate-determining.

Language: Английский

Citations

15
Enantiospecific Synthesis of Aniline-Derived Sulfonimidamides DOI Creative Commons
Dong‐Dong Liang, Natassa Lional, Bas Scheepmaker

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(30), P. 5666 - 5670

Published: July 25, 2023

Reaction of sulfonimidoyl fluorides with anilines and Ca(NTf2)2 results in the formation chiral sulfonimidamides. The reaction proceeds inversion stereocenter at a sulfur atom. Enantiospecificity was observed for all studied non-heterocyclic anilines. Combined experimental computational mechanistic studies highlight chelate-type coordination group to SN2-like transition state, which leaving F– coordinates Ca2+ ion.

Language: Английский

Citations

15
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

5
Synthesis of N‐Acylsulfenamides from (Hetero)Aryl Iodides and Boronic Acids by One‐Pot Sulfur‐Arylation and Dealkylation DOI Creative Commons
Nathaniel S. Greenwood,

Nicholas P. Cerny,

Anthony P. Deziel

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 63(3)

Published: Nov. 28, 2023

Abstract A general one‐pot approach to diverse N ‐acylsulfenamides from a common S ‐phenethylsulfenamide starting material is reported. This was demonstrated by C−S bond formation utilizing commercially abundant (hetero)aryl iodides and boronic acids provide sulfilimine intermediates that undergo thermal elimination of styrene. In contrast, all prior approaches rely on thiol inputs introduce sulfenamide ‐substituents. broad scope reaction including for approved drugs drug precursors with dense display functionality. Several different types sulfur functionalization were performed derived complex precursor the blockbuster anticoagulant apixaban, highlighting utility this introduction high oxidation state groups in bioactive compounds. Mechanistic studies established key styrene step proceeds concerted does not require reagents or catalysts, therefore, should be applicable synthesis electrophiles conditions formation.

Language: Английский

Citations

11
Bromothiolation of Arynes for the Synthesis of 2-Bromobenzenethiol Equivalents DOI Creative Commons

Shinya Tabata,

Suguru Yoshida

Organic Letters, Journal Year: 2024, Volume and Issue: 26(18), P. 3816 - 3821

Published: April 30, 2024

A new method to synthesize o-bromobenzenethiol equivalents through aryne intermediates is disclosed. Various are prepared by the bromothiolation of with potassium xanthates. Aryl xanthates serve in synthesis diverse organosulfurs involving phenothiazines and thianthrenes further transformations.

Language: Английский

Citations

4
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
Electrooxidative S-Sulfoximination of Sulfenamide: A Metal-/Catalyst-Free Green Approach DOI

Padma Priya V. R,

S. Sugapriya,

Antony Haritha Mercy A

et al.

ACS Sustainable Chemistry & Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Herein, we present a metal-/catalyst-free, novel approach for S-sulfoximination of sulfenamide. The electrooxidative reactions sulfenamides and sulfoximines are fast, high-yielding, atom-economical (99.5%), broad-substrate-tolerant, free from supporting electrolytes. protocol is ecofriendly shows wider substrate tolerance than previous reports. drug-attached sulfenamide (levetiracetam) sulfoximine (albendazole) also undergo the reaction efficiently. A possible mechanistic pathway proposed. Fascinatingly, target products obtained via photochemical in presence photocatalyst eosin Y.

Language: Английский

Citations

0