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

Sulfilimines from a Medicinal Chemist’s Perspective: Physicochemical and in Vitro Parameters Relevant for Drug Discovery DOI
Nathaniel S. Greenwood,

Zachary W. Boyer,

Jonathan A. Ellman

et al.

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

While sulfoximines are nowadays a well established functional group for medicinal chemistry, the properties of sulfilimines significantly less studied, and no sulfilimine has progressed to clinic date. In this account, physicochemical in vitro reported compared those other more traditional groups. Furthermore, impact on real drug scaffolds is studied two series sulfilimine-containing analogs imatinib hNE inhibitors. We show that can be chemically configurationally stable under physiologically relevant conditions they basic highly polar thus often beneficial solubility metabolic stability, although at cost reduced permeability. conclude S-cyclopropyl,S-(hetero)aryl S,S-di(hetero)aryl so far neglected but potentially valuable S(IV) based pharmacophores deserve considered as part chemistry toolbox.

Language: Английский

Citations

5
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

Citations

3
Dual Copper/Photoredox Catalysis for Radical-Mediated Arylation and Alkylation of Sulfenamides DOI
Mingjun Zhang,

Yuhao Tan,

Hehe Yang

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 4007 - 4016

Published: Feb. 20, 2025

Language: Английский

Citations

2
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
Cu-Catalyzed Enantioselective S-Arylation of Sulfenamides Enabled by Confined Ligands DOI
Xiaobao Wu,

Yue Shen,

Hua‐Jie Jiang

et al.

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

Published: March 20, 2025

Chiral sulfilimines, aza analogues of sulfoxides, are essential in natural products and pharmaceuticals, highlighting the importance their synthesis asymmetric catalysis. However, efficient approaches for synthesizing chiral diaryl sulfilimines still rare challenging, particularly those with two sterically similar aryl groups. Herein, we present a mild protocol generating diverse enantioenriched alkyl via copper-catalyzed enantioselective S-arylation N-acyl sulfenamides diaryliodonium salts. A bulky PyBox ligand is crucial stereocontrol, delivering various up to 95% ee (51 examples).

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
On the Sulfide Oxidation to Sulfoxides using Na3VO4 in Water DOI
Liang Yu,

Yanan SU,

Lan Liu

et al.

Chemical Communications, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

We report a simple and efficient Na3VO4-catalyzed oxidation of sulfides to sulfoxides in phosphate buffer. Optimized conditions enable broad substrate scope, including drug molecules. Isotope labeling confirms H2O2 as the oxygen donor. This cost-effective, green method offers sustainable alternative for pharmaceutical industrial sulfoxide synthesis.

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