A metal-free, iodine-catalyzed protocol has been developed for constructing biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds using aryl methyl ketones and amidoximes. The strategy produces structurally diverse 5-aroyl 1,2,4-oxadiazoles in good to excellent yields, with a broad substrate scope that includes drug derived substrates. The reaction proceeds through iodine/DMSO-mediated oxidation of aryl methyl ketones, followed by imine formation and subsequent cyclization to yield the desired products. Additionally, this protocol has successfully produced the carbonyl analogs of ataluren and tioxazafen and has facilitated some intriguing late-stage transformations.
{"title":"I2-catalyzed tandem sp3 C–H oxidation and annulation of aryl methyl ketones with amidoximes for the synthesis of 5-aroyl-1,2,4-oxadiazoles†","authors":"","doi":"10.1039/d4ob01221f","DOIUrl":"10.1039/d4ob01221f","url":null,"abstract":"<div><div>A metal-free, iodine-catalyzed protocol has been developed for constructing biologically significant 5-aroyl 1,2,4-oxadiazole scaffolds using aryl methyl ketones and amidoximes. The strategy produces structurally diverse 5-aroyl 1,2,4-oxadiazoles in good to excellent yields, with a broad substrate scope that includes drug derived substrates. The reaction proceeds through iodine/DMSO-mediated oxidation of aryl methyl ketones, followed by imine formation and subsequent cyclization to yield the desired products. Additionally, this protocol has successfully produced the carbonyl analogs of ataluren and tioxazafen and has facilitated some intriguing late-stage transformations.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhao Li, Marius Thomas, Christian M. Berač, Oliver S. Stach, Pol Besenius, John B. Matson
Self-assembled peptides provide a modular and diverse platform for drug delivery, and innovative delivery methods are needed for delivery of hydrogen sulfide (H2S), an endogenous signaling molecule (gasotransmitter) with significant therapeutic potential. Of the available types of H2S donors, peptide/protein H2S donor conjugates (PHDCs) offer significant versatility. Here we discuss the design, synthesis, and in-depth study of a PHDC containing three covalently linked components: a thiol-triggered H2S donor based on an S-aroylthiooxime (SATO), a GFFF tetrapeptide, and a tetraethylene glycol (TEG) dendron. Conventional transmission electron microscopy showed that the PHDC self-assembled into spherical structures without heat or stirring, but it formed nanofibers with gentle heat (37 °C) and stirring. Circular dichroism (CD) spectroscopy data collected during self-assembly under nanofiber-forming conditions suggested an increase in β-sheet character and a decrease in organization of the SATO units. Release of H2S from the nanofibers was studied through triggering with various thiols. The release rate and total amount of H2S released over both short (5 h) and long (7 d) time scales varied with the charge state: negatively charged and zwitterionic thiols (e.g., Ac-Cys-OH and H-Cys-OH) triggered release slowly while a neutral thiol (Ac-Cys-OMe) showed ∼10-fold faster release, and a positively charged thiol (H-Cys-OMe) triggered H2S release nearly 50-fold faster than the negatively charged thiols. CD spectroscopy studies monitoring changes in secondary structure over time during H2S release showed similar trends. This study sheds light on the driving forces behind self-assembling nanostructures and offers insights into tuning H2S release through thiol charge state modulation.
{"title":"Regulating H2S release from self-assembled peptide H2S-donor conjugates using cysteine derivatives","authors":"Zhao Li, Marius Thomas, Christian M. Berač, Oliver S. Stach, Pol Besenius, John B. Matson","doi":"10.1039/d4ob01148a","DOIUrl":"https://doi.org/10.1039/d4ob01148a","url":null,"abstract":"Self-assembled peptides provide a modular and diverse platform for drug delivery, and innovative delivery methods are needed for delivery of hydrogen sulfide (H<small><sub>2</sub></small>S), an endogenous signaling molecule (gasotransmitter) with significant therapeutic potential. Of the available types of H<small><sub>2</sub></small>S donors, peptide/protein H<small><sub>2</sub></small>S donor conjugates (PHDCs) offer significant versatility. Here we discuss the design, synthesis, and in-depth study of a PHDC containing three covalently linked components: a thiol-triggered H<small><sub>2</sub></small>S donor based on an <em>S</em>-aroylthiooxime (SATO), a GFFF tetrapeptide, and a tetraethylene glycol (TEG) dendron. Conventional transmission electron microscopy showed that the PHDC self-assembled into spherical structures without heat or stirring, but it formed nanofibers with gentle heat (37 °C) and stirring. Circular dichroism (CD) spectroscopy data collected during self-assembly under nanofiber-forming conditions suggested an increase in β-sheet character and a decrease in organization of the SATO units. Release of H<small><sub>2</sub></small>S from the nanofibers was studied through triggering with various thiols. The release rate and total amount of H<small><sub>2</sub></small>S released over both short (5 h) and long (7 d) time scales varied with the charge state: negatively charged and zwitterionic thiols (<em>e.g.</em>, Ac-Cys-OH and H-Cys-OH) triggered release slowly while a neutral thiol (Ac-Cys-OMe) showed ∼10-fold faster release, and a positively charged thiol (H-Cys-OMe) triggered H<small><sub>2</sub></small>S release nearly 50-fold faster than the negatively charged thiols. CD spectroscopy studies monitoring changes in secondary structure over time during H<small><sub>2</sub></small>S release showed similar trends. This study sheds light on the driving forces behind self-assembling nanostructures and offers insights into tuning H<small><sub>2</sub></small>S release through thiol charge state modulation.","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The nucleophilic substitution reactions involving methyl monosubstituted compounds have been studied within the Molecular Electron Density Theory (MEDT) at the ωB97X-D/6-311+G(d,p) computational level in DMSO. This study aims to characterize the electronic nature of the transition state structures (TSs) involved in the so-called SN2 and SNi reactions. Both electron localization function and atom-in-molecules topological analyses indicate that the TSs involved in these nucleophilic substitutions can be described as a central methyl CH3+ carbocation, which is strongly stabilized by the presence of two neighbouring nucleophilic species through electron density transfer. This MEDT study establishes a significant electronic similarity between the so-called SN1 and SN2 reactions. Due to the weak electrophilic character of the methyl tetrahedral carbons, the departure of the leaving group should be expected with the approach of the nucleophile. However, while along the SN1 reactions, the strong stabilization of the tertiary carbocation does not demand the participation of the nucleophile, along the SN2 and SNi reactions involving primary tetrahedral carbons, the nucleophiles should participate in the reaction to stabilize the unstable methyl carbocation.
{"title":"A molecular electron density theory study of the bimolecular nucleophilic substitution reactions on monosubstituted methyl compounds†","authors":"","doi":"10.1039/d4ob01113a","DOIUrl":"10.1039/d4ob01113a","url":null,"abstract":"<div><div>The nucleophilic substitution reactions involving methyl monosubstituted compounds have been studied within the Molecular Electron Density Theory (MEDT) at the <em>ω</em>B97X-D/6-311+G(d,p) computational level in DMSO. This study aims to characterize the electronic nature of the transition state structures (TSs) involved in the so-called S<sub>N</sub>2 and S<sub>N</sub>i reactions. Both electron localization function and atom-in-molecules topological analyses indicate that the TSs involved in these nucleophilic substitutions can be described as a central methyl CH<sub>3</sub><sup>+</sup> carbocation, which is strongly stabilized by the presence of two neighbouring nucleophilic species through electron density transfer. This MEDT study establishes a significant electronic similarity between the so-called S<sub>N</sub>1 and S<sub>N</sub>2 reactions. Due to the weak electrophilic character of the methyl tetrahedral carbons, the departure of the leaving group should be expected with the approach of the nucleophile. However, while along the S<sub>N</sub>1 reactions, the strong stabilization of the tertiary carbocation does not demand the participation of the nucleophile, along the S<sub>N</sub>2 and S<sub>N</sub>i reactions involving primary tetrahedral carbons, the nucleophiles should participate in the reaction to stabilize the unstable methyl carbocation.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Small-molecule sensors that are selective for particular sugars are rare. The synthesis of BODIPYs appended with two boronic acid units is reported, alongside cellular staining/labelling and turn-on fluorescence binding data for carbohydrates. The structural frameworks were designed using computational methods, leaning on the chelation characteristics of bis(boronic acids) and the photophysical properties of BODIPYs. Selective binding to glucose is demonstrated via emission and absorption methods, and the challenges of using NMR data for studying carbohydrate binding are discussed. Furthermore, crystal structures, cell permeability and imaging properties of the BODIPYs appended with two boronic acid units are described. This work presents boronic-acid-appended BODIPYs as a potential framework for tunable carbohydrate sensing and chemical biology staining.
{"title":"BODIPYs α-appended with distyryl-linked aryl bisboronic acids: single-step cell staining and turn-on fluorescence binding with d-glucose†","authors":"","doi":"10.1039/d4ob01013b","DOIUrl":"10.1039/d4ob01013b","url":null,"abstract":"<div><div>Small-molecule sensors that are selective for particular sugars are rare. The synthesis of BODIPYs appended with two boronic acid units is reported, alongside cellular staining/labelling and turn-on fluorescence binding data for carbohydrates. The structural frameworks were designed using computational methods, leaning on the chelation characteristics of bis(boronic acids) and the photophysical properties of BODIPYs. Selective binding to glucose is demonstrated <em>via</em> emission and absorption methods, and the challenges of using NMR data for studying carbohydrate binding are discussed. Furthermore, crystal structures, cell permeability and imaging properties of the BODIPYs appended with two boronic acid units are described. This work presents boronic-acid-appended BODIPYs as a potential framework for tunable carbohydrate sensing and chemical biology staining.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The β-arylethylamine pharmacophore is commonly found in medications for central nervous system disorders, prompting the need for safe and efficient methods to endow this motif with relevant functional groups for drug discovery. In this context, herein, we have established electrochemical radical sulfonylation reactions of N-allylbenzamides followed by Truce–Smiles rearrangement to produce sulfone- and sulfonate ester-containing β-arylethylamines. Electricity enables this transformation to occur under mild and oxidant-free conditions. Simple sources of sulfonyl radicals and SO2 surrogates were employed to form sulfones and sulfonate esters, respectively. This practical and operationally robust method exhibited a broad substrate scope with good to high yields. The prospective pharmaceutical utility of the process was further demonstrated by removing the N-protecting groups and hydrolysing the sulfonate ester moiety to provide γ-sulfonyl-β-arylamines and Saclofen.
在治疗中枢神经系统疾病的药物中，β-芳基乙胺药理结构十分常见，因此需要采用安全高效的方法为这一基团赋予相关官能团，以促进药物发现。在此背景下，我们建立了 N-烯丙基苯甲酰胺的电化学自由基磺酰化反应，然后通过 Truce-Smiles 重排生成含砜和磺酸酯的β-芳基乙胺。电能使这种转化在温和、无氧化剂的条件下进行。利用简单的磺酰基和二氧化硫代用品分别形成砜和磺酸酯。这种实用且操作性强的方法具有广泛的底物范围和良好的产率。通过移除 N 保护基团和水解磺酸酯基团，制备出 γ-磺酰基-β-芳胺和沙氯芬，进一步证明了该方法在制药方面的应用前景。
{"title":"Electrochemical sulfonylation/Truce–Smiles rearrangement of N-allylbenzamides: toward sulfone-containing β-arylethylamines and Saclofen analogues","authors":"Sébastien Meyer, Alexandre Neuhut, Aurélie Claraz","doi":"10.1039/d4ob01327a","DOIUrl":"https://doi.org/10.1039/d4ob01327a","url":null,"abstract":"The β-arylethylamine pharmacophore is commonly found in medications for central nervous system disorders, prompting the need for safe and efficient methods to endow this motif with relevant functional groups for drug discovery. In this context, herein, we have established electrochemical radical sulfonylation reactions of <em>N</em>-allylbenzamides followed by Truce–Smiles rearrangement to produce sulfone- and sulfonate ester-containing β-arylethylamines. Electricity enables this transformation to occur under mild and oxidant-free conditions. Simple sources of sulfonyl radicals and SO<small><sub>2</sub></small> surrogates were employed to form sulfones and sulfonate esters, respectively. This practical and operationally robust method exhibited a broad substrate scope with good to high yields. The prospective pharmaceutical utility of the process was further demonstrated by removing the <em>N</em>-protecting groups and hydrolysing the sulfonate ester moiety to provide γ-sulfonyl-β-arylamines and Saclofen.","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A protein modification strategy was developed based on a thiol–yne click reaction using an electron-deficient yne reagent. This approach demonstrated exceptional selectivity towards thiols and exhibited rapid kinetics, resulting in conjugates with superior acid stability. The conjugation of IgG with an indole-derived fluorophore was achieved for the imaging of PD-L1 in cancer cells.
{"title":"A thiol-selective and acid-stable protein modification strategy using an electron-deficient yne reagent†","authors":"","doi":"10.1039/d4ob01037j","DOIUrl":"10.1039/d4ob01037j","url":null,"abstract":"<div><div>A protein modification strategy was developed based on a thiol–yne click reaction using an electron-deficient yne reagent. This approach demonstrated exceptional selectivity towards thiols and exhibited rapid kinetics, resulting in conjugates with superior acid stability. The conjugation of IgG with an indole-derived fluorophore was achieved for the imaging of PD-L1 in cancer cells.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Susannah H. Calvert, Tomasz Pawlak, Gary Hessman, Joanna F. McGouran
Azide functionalization of protein and peptide lysine residues allows selective bioorthogonal labeling to introduce new, site selective functionaltiy into proteins. Optimised diazotransfer reactions under mild conditions allow aqueous diazotransfer to occur in just 20 min at pH 8.5 on amino acid, peptide and protein targets. In addition, conditons can be modified to selectively label a single lysine residue in both protein targets investigated. Finally, we demonstrate selective modification of proteins containing a single azidolysine using copper(I)-catalyzed triazole formation.
{"title":"Rapid diazotransfer for selective lysine labelling","authors":"Susannah H. Calvert, Tomasz Pawlak, Gary Hessman, Joanna F. McGouran","doi":"10.1039/d4ob01094a","DOIUrl":"https://doi.org/10.1039/d4ob01094a","url":null,"abstract":"Azide functionalization of protein and peptide lysine residues allows selective bioorthogonal labeling to introduce new, site selective functionaltiy into proteins. Optimised diazotransfer reactions under mild conditions allow aqueous diazotransfer to occur in just 20 min at pH 8.5 on amino acid, peptide and protein targets. In addition, conditons can be modified to selectively label a single lysine residue in both protein targets investigated. Finally, we demonstrate selective modification of proteins containing a single azidolysine using copper(<small>I</small>)-catalyzed triazole formation.","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaokun Zhang, Chaochun Wei, Keli Zong, Qidi Zhong, Hong Yan
Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market for a variety of applications, but one notable omission is that of tetraasteranes, which are homologues of cubanes belonging to a class of polycyclic hydrocarbon cage compounds. Tetraasteranes exhibit potential as scaffolds in drug discovery due to their identical cyclobutane structures and rigid conformation resembling cubanes. Based on the studies of the physical and chemical properties of tetraasteranes by density functional theory, three series of compounds were designed as homologues of cubanes by the substitution of cubane scaffolds in pharmaceuticals with tetraasteranes. Their potential for pharmaceutical applications was evaluated in silico by molecular docking and dynamics simulations. Their pharmacokinetic and physicochemical properties were studied by the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The results indicate that tetraasteranes may be scaffolds as novel bioisosteres of cubanes, as well as hydrogen bond donors or acceptors, which enhance the affinity between ligands and receptors with more stable binding behavior and feasible tolerability in ADMET. All these findings provide new opportunities for tetraasteranes to serve as effective pharmaceutical scaffolds for drug discovery and to accelerate the drug discovery process by repurposing both new and old commercial compounds.
{"title":"Tetraasteranes as homologues of cubanes: effective scaffolds for drug discovery","authors":"Xiaokun Zhang, Chaochun Wei, Keli Zong, Qidi Zhong, Hong Yan","doi":"10.1039/d4ob01043d","DOIUrl":"https://doi.org/10.1039/d4ob01043d","url":null,"abstract":"Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market for a variety of applications, but one notable omission is that of tetraasteranes, which are homologues of cubanes belonging to a class of polycyclic hydrocarbon cage compounds. Tetraasteranes exhibit potential as scaffolds in drug discovery due to their identical cyclobutane structures and rigid conformation resembling cubanes. Based on the studies of the physical and chemical properties of tetraasteranes by density functional theory, three series of compounds were designed as homologues of cubanes by the substitution of cubane scaffolds in pharmaceuticals with tetraasteranes. Their potential for pharmaceutical applications was evaluated <em>in silico</em> by molecular docking and dynamics simulations. Their pharmacokinetic and physicochemical properties were studied by the ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis. The results indicate that tetraasteranes may be scaffolds as novel bioisosteres of cubanes, as well as hydrogen bond donors or acceptors, which enhance the affinity between ligands and receptors with more stable binding behavior and feasible tolerability in ADMET. All these findings provide new opportunities for tetraasteranes to serve as effective pharmaceutical scaffolds for drug discovery and to accelerate the drug discovery process by repurposing both new and old commercial compounds.","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142202345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
l-Cysteine (Cys)-activatable photosensitizer 3 was designed and synthesized based on hypocrellin B (1). Cys is a novel tumor-associated biomarker. 3 exhibited negligible photosensitizing ability without Cys. However, when 1 was released from 3 by reaction with Cys, the photosensitizing activity was restored. Furthermore, 3 showed selective and effective photo-cytotoxicity against only cancer cells such as HeLa and A549 cells that highly express Cys when irradiated with 660 nm light, which is inside the phototherapeutic window.
{"title":"A novel photosensitizer based on hypocrellin B activated by cysteine over-expressed in cancer cells†","authors":"","doi":"10.1039/d4ob01288g","DOIUrl":"10.1039/d4ob01288g","url":null,"abstract":"<div><div> <span>l</span>-Cysteine (Cys)-activatable photosensitizer <strong>3</strong> was designed and synthesized based on hypocrellin B (<strong>1</strong>). Cys is a novel tumor-associated biomarker. <strong>3</strong> exhibited negligible photosensitizing ability without Cys. However, when <strong>1</strong> was released from <strong>3</strong> by reaction with Cys, the photosensitizing activity was restored. Furthermore, <strong>3</strong> showed selective and effective photo-cytotoxicity against only cancer cells such as HeLa and A549 cells that highly express Cys when irradiated with 660 nm light, which is inside the phototherapeutic window.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Conventionally, carbenium and onium ions are prepared in the presence of nucleophiles due to their instability and transient nature. The nucleophiles that are unstable or inert to the reaction media cannot be used for reaction with the cationic species to access the desired compounds. To overcome these limitations, developing methods for generating organic cations irreversibly in the absence of nucleophiles is essential. The “cation pool” method developed by Yoshida and co-workers stands out as a reliable strategy to generate and accumulate the reactive cations in solution in the absence of nucleophiles. The cation pool method involves the electrolysis of the substrate in the absence of nucleophiles, usually at low temperature. Moreover, the generation of halogen and chalcogen cations through electrolysis needs extra care because of their low stability. This review covers our effort in generating and accumulating halogen cations as “cation pools”, most importantly by simply heating a mixture of dimethyl sulfoxide (DMSO) and 1,2-dihaloethane (DXE, X = Cl, Br, I), and their use in the halogenation reactions. Furthermore, condition-dependent Pummerer-type fragmentations of DMSO-stabilized halogen cations to methyl(methylene)sulfonium ions and chlorodimethylsulfonium ions for synthetic applications are described.
{"title":"“Cation Pool” generated from DMSO and 1,2-dihaloethanes and their application in organic synthesis","authors":"","doi":"10.1039/d4ob00740a","DOIUrl":"10.1039/d4ob00740a","url":null,"abstract":"<div><div>Conventionally, carbenium and onium ions are prepared in the presence of nucleophiles due to their instability and transient nature. The nucleophiles that are unstable or inert to the reaction media cannot be used for reaction with the cationic species to access the desired compounds. To overcome these limitations, developing methods for generating organic cations irreversibly in the absence of nucleophiles is essential. The “cation pool” method developed by Yoshida and co-workers stands out as a reliable strategy to generate and accumulate the reactive cations in solution in the absence of nucleophiles. The cation pool method involves the electrolysis of the substrate in the absence of nucleophiles, usually at low temperature. Moreover, the generation of halogen and chalcogen cations through electrolysis needs extra care because of their low stability. This review covers our effort in generating and accumulating halogen cations as “cation pools”, most importantly by simply heating a mixture of dimethyl sulfoxide (DMSO) and 1,2-dihaloethane (DXE, X = Cl, Br, I), and their use in the halogenation reactions. Furthermore, condition-dependent Pummerer-type fragmentations of DMSO-stabilized halogen cations to methyl(methylene)sulfonium ions and chlorodimethylsulfonium ions for synthetic applications are described.</div></div>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142034581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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