Heteroaryl sulfonamides are important structural motifs in the medicinal and agrochemical industries. However, their synthesis often relies on the use of heteroaryl sulfonyl chlorides, which are unstable and toxic reagents. Herein, we report a protocol that allows direct oxidative coupling of heteroaryl thiols and primary amines, readily available and inexpensive commodity chemicals. The transformation proceeds under mild reaction conditions and yields the desired -alkylated sulfonamides in good yields. -alkyl heteroaryl sulfonamides can be further transformed using a microwave-promoted Fukuyama-Mitsunobu reaction to ,-dialkyl heteroaryl sulfonamides. The developed protocols thus enable the preparation of previously difficult to prepare sulfonamides (toxic reagents, harsh conditions, and low yields) under mild conditions.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1039/d2ob00345g | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
F-Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [F]Fluoride.
Org Lett
November 2024
Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA, United Kingdom.
Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative F-fluorodecarboxylation with [F]fluoride affording biologically relevant F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including -heteroarylation and amide as well as sulfonamide bond formation.
View Article and Find Full Text PDFConversion of Carboxylic Acids to Sulfonamide Bioisosteres via Energy Transfer Photocatalysis.
Org Lett
October 2024
School of Pharmaceutical and Chemical Engineering and Institute for Advanced Studies, Taizhou University, Taizhou 318000, China.
Article Synopsis
- Over 450 drugs with carboxylic acid functional groups are on the market globally.
- The study presents an eco-friendly method to convert carboxylic acids into bioisosteres using light.
- This approach efficiently transforms various types of acids, including alkyl and biologically important acids, into primary sulfonamides.
Sulfonamide-directed site-selective functionalization of unactivated C(sp)-H enabled by photocatalytic sequential electron/proton transfer.
Nat Commun
June 2024
Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou, P. R. of China.
The generation of alkyl radical from C(sp)-H substrates via hydrogen atom abstraction represents a desirable yet underexplored strategy in alkylation reaction since involving common concerns remain adequately unaddressed, such as the harsh reaction conditions, limited substrate scope, and the employment of noble metal- or photo-catalysts and stoichiometric oxidants. Here, we utilize the synergistic strategy of photoredox and hydrogen atom transfer (HAT) catalysis to accomplish a general and practical functionalization of unactived C(sp)-H centers with broad reaction scope, high functional group compatibility, and operational simplicity. A combination of validation experiments and density functional theory reveals that the N-centered radicals, generated from free N - H bond in a stepwise electron/proton transfer event, are the key intermediates that enable an intramolecular 1,5-HAT or intermolecular HAT process for nucleophilic carbon-centered radicals formation to achieve heteroarylation, alkylation, amination, cyanation, azidation, trifluoromethylthiolation, halogenation and deuteration.
View Article and Find Full Text PDFMetal-Free Photoredox Catalyzed Sulfonylation of Phenylhydrazines with Thiols.
Org Lett
May 2024
Department of Chemistry, Indian Institute of Technology (BHU), Varanasi - 221 005, U.P., India.
The sulfonylation method stands out as a simple and efficient approach for synthesizing sulfonamides. Despite the advancements in constructing the sulfonamide framework, the potential use of phenyl hydrazine as an amination source remains unexplored. Herein, we report a metal-free, environment-friendly photoredox-catalyzed sulfonylation of phenylhydrazines using thiols, employing MeCN:HO as a green solvent and eosin Y as a photoredox catalyst.
View Article and Find Full Text PDFThermal Nickel-Catalyzed -Arylation of NH-Sulfoximines with (Hetero)aryl Chlorides Enabled by PhPAd-DalPhos Ligation.
Org Lett
February 2024
Department of Chemistry, Dalhousie University, 6274 Coburg Road, Halifax, Nova Scotia B3H 4R2, Canada.
We report a versatile method for cross-coupling of -sulfoximines with (hetero)aryl chlorides, as well as bromide and sulfonate electrophiles, that makes use of the air-stable, commercial precatalyst (PhPAd-DalPhos)Ni(-tol)Cl. Under optimized conditions a diverse electrophile scope is established, including the -arylation of the pharmaceutical Clozapine. While 5 mol % Ni and 80 °C are commonly employed in this chemistry, successful examples utilizing 1 mol % Ni and/or 25 °C are presented.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!