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

Synthesis of Chiral Sulfonimidoyl Chloride via Desymmetrizing Enantioselective Hydrolysis DOI

Gao-feng Yang,

Yi Yuan, Tian Yin

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(9), P. 5439 - 5446

Published: Feb. 22, 2023

Direct construction of chiral S(VI) from prochiral S(II) is a formidable challenge due to the inevitable formation stable S(IV). Previous synthetic strategies rely on conversion S(IV) or enantioselective desymmetrization preformed symmetrical substrates. Here, we report desymmetrizing hydrolysis in situ-generated symmetric aza-dichlorosulfonium sulfenamides for preparation sulfonimidoyl chlorides, which could be used as general synthon obtaining series derivatives.

Language: Английский

Citations

62
Asymmetric Synthesis of S(IV) and S(VI) Stereogenic Centers DOI Creative Commons
Xin Zhang, Fu‐Cheng Wang, Choon‐Hong Tan

et al.

JACS Au, Journal Year: 2023, Volume and Issue: 3(3), P. 700 - 714

Published: Feb. 28, 2023

Sulfur can form diverse S(IV) and S(VI) stereogenic centers, of which some have gained significant attention recently due to their increasing use as pharmacophores in drug discovery programs. The preparation these sulfur centers enantiopure has been challenging, progress made will be discussed this Perspective. This Perspective summarizes different strategies, with selected works, for asymmetric synthesis moieties, including diastereoselective transformations using chiral auxiliaries, enantiospecific compounds, catalytic enantioselective synthesis. We discuss the advantages limitations strategies provide our views on how field develop.

Language: Английский

Citations

57
Enantioselective construction of stereogenic-at-sulfur(IV) centres via catalytic acyl transfer sulfinylation DOI
Tao Wei,

Han‐Le Wang,

Tian Yin

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1301 - 1311

Published: May 8, 2024

Language: Английский

Citations

21
Electrooxidative Rhodium(III)/Chiral Carboxylic Acid‐Catalyzed Enantioselective C−H Annulation of Sulfoximines with Alkynes DOI
Gang Zhou, Tao Zhou,

Ao‐Lian Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(15)

Published: Jan. 30, 2024

Abstract The combination of achiral Cp*Rh(III) with chiral carboxylic acids (CCAs) represents an efficient catalytic system in transition metal‐catalyzed enantioselective C−H activation. However, this hybrid catalysis is limited to redox‐neutral activation reactions and the adopt oxidative remains elusive pose a significant challenge. Herein, we describe development electrochemical Cp*Rh(III)‐catalyzed annulation sulfoximines alkynes enabled by acid (CCA) operationally friendly undivided cell at room temperature. A broad range enantioenriched 1,2‐benzothiazines are obtained high yields excellent enantioselectivities (up 99 % yield 98 : 2 er). practicality method demonstrated scale‐up reaction batch reactor external circulation. crucial intermediate isolated, characterized, transformed, providing rational support for Rh(III)/Rh(I) electrocatalytic cycle.

Language: Английский

Citations

20
Synthesis of Sulfur-Stereogenic Sulfoximines via Co(III)/Chiral Carboxylic Acid-Catalyzed Enantioselective C–H Amidation DOI
Yibo Zhou, Tao Zhou, Pu‐Fan Qian

et al.

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(15), P. 9806 - 9811

Published: July 27, 2022

Sulfoximines bearing stereogenic sulfur atoms are ubiquitous motifs in pharmaceuticals, agricultural chemicals, and bioactive compounds. Herein, we report the synthesis of sulfur-stereogenic sulfoximines via Co(III)/chiral carboxylic acid-catalyzed enantioselective C–H amidation. A broad range cyclic acyclic were isolated good yields enantioselectivities (up to an 86% yield 1.5:98.5 er). The amidation products can be reduced potential N,S-chiral sulfoxide ligands, which could further transformed into recyclable chiral auxiliaries Pd-catalyzed diastereoselective C(sp3)–H activation aliphatic acids.

Language: Английский

Citations

62
Organocatalytic asymmetric deoxygenation of sulfones to access chiral sulfinyl compounds DOI
Sheng‐Li Huang, Zhen Zeng, Nan Zhang

et al.

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(2), P. 185 - 193

Published: Jan. 16, 2023

Language: Английский

Citations

36
One-Pot Tandem Oxidative Bromination and Amination of Sulfenamide for the Synthesis of Sulfinamidines DOI

Gao-feng Yang,

He-sen Huang,

Xiao‐kang Nie

et al.

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(7), P. 4581 - 4591

Published: March 16, 2023

The sulfinamidines as aza analogues of sulfinamides received limited attention from both organic chemists and pharmaceutical chemists. Herein, we present a tandem oxidative/nucleophilic substitution approach for the synthesis in high yield (up to 98%). This cascade reaction method is enabled by N-bromosuccinimide (NBS) an oxidant diverse readily available amines nucleophiles without any additives or catalysts. Notably, this highly time-economical, safe operate, easy scale up has excellent functional group compatibility.

Language: Английский

Citations

32
Strain-promoted S-arylation and alkenylation of sulfinamides using arynes and cyclic alkynes DOI
Xi Zou,

Boming Shen,

Gaolin Li

et al.

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(3), P. 928 - 935

Published: Jan. 15, 2024

Language: Английский

Citations

11
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

2
Design and Application of Peptide‐Mimic Phosphonium Salt Catalysts in Asymmetric Synthesis DOI

Siqiang Fang,

Zanjiao Liu,

Tianli Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(47)

Published: July 6, 2023

Chiral phosphonium salt catalysis, traditionally classified as a type of phase transfer has proven to be powerful strategy for the stereoselective preparation diverse optically active molecules. However, there still remain numerous forbidding issues reactivity and selectivity in such well-known organocatalysis system. Accordingly, development new high-performance catalysts with unique chiral backbones is highly desirable, yet challenging. This Minireview describes prominent endeavours family peptide-mimic multiple hydrogen-bonding donors their applications plethora enantioselective synthesis during past few years. Hopefully, this minireview will pave way further developing much more efficient privileged ligands/catalysts featuring exclusively catalytic ability asymmetric synthesis.

Language: Английский

Citations

22