Xidong Ye, Zengguang Li, Shangde Ye, Xinqi Liang, Chenyu Bao, Mingyang He, Hailan Wang, Laixin Xia, Xin Cao
8-oxoguanine (o8G), a prevalent oxidative modification in RNA induced by reactive oxygen species (ROS), plays a pivotal role in regulating RNA functions. Accurate detection and quantification of o8G modifications is critical to understanding their biological significance and potential as disease biomarkers, but effective detection methods remain limited. Here, we have developed a highly specific T3 DNA ligase-dependent qPCR assay that exploits the enzyme's ability to discriminate o8G from guanine (G) with single-nucleotide resolution. This method can detect o8G in RNA at levels as low as 500 fM, with an up to 18-fold higher selectivity for discriminating o8G from G. By simulating oxidative stress conditions in SH-SY5Y and HS683 cell lines treated with rotenone, we successfully identified site-specific o8G modifications in key miRNAs associated with neuroprotective responses, including miR-124, let-7a and miR-29a. The developed assay holds significant promise for the practical identification of o8G, facilitating its potential for detailed studies of o8G dynamics in various biological contexts and diseases.
{"title":"Accurate identification of 8-oxoguanine in RNA with single-nucleotide resolution using ligase-dependent qPCR.","authors":"Xidong Ye, Zengguang Li, Shangde Ye, Xinqi Liang, Chenyu Bao, Mingyang He, Hailan Wang, Laixin Xia, Xin Cao","doi":"10.1039/d4ob00786g","DOIUrl":"https://doi.org/10.1039/d4ob00786g","url":null,"abstract":"<p><p>8-oxoguanine (o<sup>8</sup>G), a prevalent oxidative modification in RNA induced by reactive oxygen species (ROS), plays a pivotal role in regulating RNA functions. Accurate detection and quantification of o<sup>8</sup>G modifications is critical to understanding their biological significance and potential as disease biomarkers, but effective detection methods remain limited. Here, we have developed a highly specific T3 DNA ligase-dependent qPCR assay that exploits the enzyme's ability to discriminate o<sup>8</sup>G from guanine (G) with single-nucleotide resolution. This method can detect o<sup>8</sup>G in RNA at levels as low as 500 fM, with an up to 18-fold higher selectivity for discriminating o<sup>8</sup>G from G. By simulating oxidative stress conditions in SH-SY5Y and HS683 cell lines treated with rotenone, we successfully identified site-specific o<sup>8</sup>G modifications in key miRNAs associated with neuroprotective responses, including miR-124, let-7a and miR-29a. The developed assay holds significant promise for the practical identification of o<sup>8</sup>G, facilitating its potential for detailed studies of o<sup>8</sup>G dynamics in various biological contexts and diseases.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441847","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}
Mengfan Li, Yan Chen, Hao Tang, Wen Cheng, Benren Liao, Qingwei Wang, Weiyin Yi
An efficient and metal-free method for the synthesis of 3-aryl pyrido[1,2-a]indoles from aryne intermediates and 2-pyridinyl-substituted p-QMs was successfully developed under ambient conditions. The reaction offered a novel and practical protocol to access some diverse functional molecules in good to excellent yields. The proposed mechanism indicated that the reaction proceeded via a formal [3 + 2] cycloaddition step.
{"title":"One-pot formal [3 + 2] annulation of 2-pyridinyl-substituted <i>p</i>-quinone methides and arynes for the synthesis of 3-aryl pyrido[1,2-<i>a</i>]indoles.","authors":"Mengfan Li, Yan Chen, Hao Tang, Wen Cheng, Benren Liao, Qingwei Wang, Weiyin Yi","doi":"10.1039/d4ob00684d","DOIUrl":"https://doi.org/10.1039/d4ob00684d","url":null,"abstract":"<p><p>An efficient and metal-free method for the synthesis of 3-aryl pyrido[1,2-<i>a</i>]indoles from aryne intermediates and 2-pyridinyl-substituted <i>p</i>-QMs was successfully developed under ambient conditions. The reaction offered a novel and practical protocol to access some diverse functional molecules in good to excellent yields. The proposed mechanism indicated that the reaction proceeded <i>via</i> a formal [3 + 2] cycloaddition step.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441848","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}
Ani Deepthi, Sruthi Sudheendran Leena, Devika Krishnan
Thiopyrans and their fused derivatives have significant synthetic relevance owing to their biological importance and occurrence in natural products. The current article provides an overview of synthetic strategies employed for the construction of thiopyran-fused heterocycles. In particular, this article discusses synthetic methods for the fusion of thiopyran with heterocycles such as indole, quinoline, pyrimidine, pyridine, thiophene, chromene, oxazole, pyrazole, pyran and furan and covers the literature from 2013 to 2024. The most common precursors for thiopyrano[2,3-b]indoles, thiopyranoquinolines and thiopyranothiazoles are indoline-2-thione, 2-mercaptoquinoline-3-carbaldehyde and thiazolidinone, respectively, and various reactions involving these are described in detail here. Asymmetric syntheses of thiopyranoindoles achieved using chiral catalysts based on thiourea, proline and metal complexes are also included. The biological activity associated with some compounds is also discussed.
{"title":"Update on thiopyran-fused heterocycle synthesis (2013-2024).","authors":"Ani Deepthi, Sruthi Sudheendran Leena, Devika Krishnan","doi":"10.1039/d4ob00497c","DOIUrl":"https://doi.org/10.1039/d4ob00497c","url":null,"abstract":"<p><p>Thiopyrans and their fused derivatives have significant synthetic relevance owing to their biological importance and occurrence in natural products. The current article provides an overview of synthetic strategies employed for the construction of thiopyran-fused heterocycles. In particular, this article discusses synthetic methods for the fusion of thiopyran with heterocycles such as indole, quinoline, pyrimidine, pyridine, thiophene, chromene, oxazole, pyrazole, pyran and furan and covers the literature from 2013 to 2024. The most common precursors for thiopyrano[2,3-<i>b</i>]indoles, thiopyranoquinolines and thiopyranothiazoles are indoline-2-thione, 2-mercaptoquinoline-3-carbaldehyde and thiazolidinone, respectively, and various reactions involving these are described in detail here. Asymmetric syntheses of thiopyranoindoles achieved using chiral catalysts based on thiourea, proline and metal complexes are also included. The biological activity associated with some compounds is also discussed.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441849","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}
Ajay G Mamale, Sayantan Paul, Rajesh G Gonnade, Asish K Bhattacharya
Herein we report a transition-metal free, base-mediated 1,6-conjugate addition of aryldiazenes to para-quinone methides (p-QMs). Arylhydrazines were used for the in situ generation of aryldiazenes using a base-mediated protocol in the presence of air as the oxidant. The 1,6-conjugate addition of aryldiazenes to para-quinone methides via a radical mechanism is followed by an oxidative rearrangement to furnish the desired product, arylhydrazones. Interestingly, our synthetic protocol results in the formation of an aryldiazene radical, which undergoes 1,6-conjugate addition with p-QMs to furnish the arylhydrazones.
{"title":"1,6-Conjugate addition of <i>in situ</i> generated aryldiazenes to <i>p</i>-quinone methides.","authors":"Ajay G Mamale, Sayantan Paul, Rajesh G Gonnade, Asish K Bhattacharya","doi":"10.1039/d4ob00618f","DOIUrl":"https://doi.org/10.1039/d4ob00618f","url":null,"abstract":"<p><p>Herein we report a transition-metal free, base-mediated 1,6-conjugate addition of aryldiazenes to <i>para</i>-quinone methides (<i>p</i>-QMs). Arylhydrazines were used for the <i>in situ</i> generation of aryldiazenes using a base-mediated protocol in the presence of air as the oxidant. The 1,6-conjugate addition of aryldiazenes to <i>para</i>-quinone methides <i>via</i> a radical mechanism is followed by an oxidative rearrangement to furnish the desired product, arylhydrazones. Interestingly, our synthetic protocol results in the formation of an aryldiazene radical, which undergoes 1,6-conjugate addition with <i>p</i>-QMs to furnish the arylhydrazones.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441846","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}
Herein, we disclose the synthesis of a variety of disubstituted fused quinoline, such as 4-methyl-2-arylbenzo[h]quinolines (3a-j), 1-methyl-3-arylbenzo[f]quinolines (3k-r), 1-methyl-3-arylnaphtho[2,3-f]quinolines (3s-x), and 2-aryl-5,7-dimethoxy-4-methylquinolines (4a-c), derivatives from the reaction of an aryl aldehyde with 1-naphthylamine (1a), 2-naphthylamine (1b), 2-aminoanthracene (1c) and 3,5-dimethoxyaniline (1d), respectively, at 80 °C in the presence of 30 mol% (±)-10-camphorsulfonic acid ((±)-CSA) using DMSO as the solvent-cum-reactant. DMSO molecules regioselectively incorporate three carbon atoms into the target molecule in this distinct reaction. The other advantages of the present protocol are that it can be performed under mild reaction conditions and does not require metal catalysts, additional additives or oxidants.
{"title":"Utilization of DMSO as a solvent-cum-reactant: synthesis of fused 2-aryl-4-methylquinolines.","authors":"Sabina Yashmin, Karthik A M, Abu Taleb Khan","doi":"10.1039/d4ob00938j","DOIUrl":"https://doi.org/10.1039/d4ob00938j","url":null,"abstract":"<p><p>Herein, we disclose the synthesis of a variety of disubstituted fused quinoline, such as 4-methyl-2-arylbenzo[<i>h</i>]quinolines (3a-j), 1-methyl-3-arylbenzo[<i>f</i>]quinolines (3k-r), 1-methyl-3-arylnaphtho[2,3-<i>f</i>]quinolines (3s-x), and 2-aryl-5,7-dimethoxy-4-methylquinolines (4a-c), derivatives from the reaction of an aryl aldehyde with 1-naphthylamine (1a), 2-naphthylamine (1b), 2-aminoanthracene (1c) and 3,5-dimethoxyaniline (1d), respectively, at 80 °C in the presence of 30 mol% (±)-10-camphorsulfonic acid ((±)-CSA) using DMSO as the solvent-cum-reactant. DMSO molecules regioselectively incorporate three carbon atoms into the target molecule in this distinct reaction. The other advantages of the present protocol are that it can be performed under mild reaction conditions and does not require metal catalysts, additional additives or oxidants.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141441850","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}
Marco M D Cominetti, Zoë R Goddard, Bethany R Hood, Andrew M Beekman, Maria A O'Connell, Mark Searcey
The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.
利用市场上可买到的起始原料,通过十一个线性步骤合成了超强抗肿瘤抗生素 seco-duocarmycin SA 的乙酯类似物。DSA烷基化亚基可由相同的前体通过十个线性步骤制成。该方法涉及在吲哚上相当于 C7 位置的 C-H 活化,从而产生硼烷基化的中间体 9,该中间体足够稳定,可用于肽偶联反应,但很容易转化为游离的羟基类似物。
{"title":"Borylation <i>via</i> iridium catalysed C-H activation: a new concise route to duocarmycin derivatives.","authors":"Marco M D Cominetti, Zoë R Goddard, Bethany R Hood, Andrew M Beekman, Maria A O'Connell, Mark Searcey","doi":"10.1039/d4ob00814f","DOIUrl":"https://doi.org/10.1039/d4ob00814f","url":null,"abstract":"<p><p>The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430967","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}
Guijun Wang, Anji Chen, Pramod Aryal, Jonathan Bietsch
Carbohydrate-based self-assembling systems are essential for the formation of advanced biocompatible materials via a bottom-up approach. The self-assembling of sugar-based small molecules has applications encompassing many research fields and has been studied extensively. In this focused review, we will discuss the synthetic approaches for carbohydrate-based self-assembling (SA) systems, the mechanisms of the assembly, as well as the main properties and applications. This review will mainly cover recent publications in the last four years from January 2020 to December 2023. We will essentially focus on small molecule self-assembly, excluding polymer-based systems, which include various derivatives of monosaccharides, disaccharides, and oligosaccharides. Glycolipids, glycopeptides, and some glycoconjugate-based systems are discussed. Typically, in each category of systems, the system that can function as low molecular weight gelators (LMWGs) will be discussed first, followed by self-assembling systems that produce micelles and aggregates. The last section of the review discusses stimulus-responsive self-assembling systems, especially those forming gels, including dynamic covalent assemblies, chemical-triggered systems, and photoresponsive systems. The review will be organized based on the sugar structures, and in each category, the synthesis of representative molecular systems will be discussed next, followed by the properties of the resulting molecular assemblies.
{"title":"Synthetic approaches of carbohydrate based self-assembling systems.","authors":"Guijun Wang, Anji Chen, Pramod Aryal, Jonathan Bietsch","doi":"10.1039/d4ob00636d","DOIUrl":"https://doi.org/10.1039/d4ob00636d","url":null,"abstract":"<p><p>Carbohydrate-based self-assembling systems are essential for the formation of advanced biocompatible materials <i>via</i> a bottom-up approach. The self-assembling of sugar-based small molecules has applications encompassing many research fields and has been studied extensively. In this focused review, we will discuss the synthetic approaches for carbohydrate-based self-assembling (SA) systems, the mechanisms of the assembly, as well as the main properties and applications. This review will mainly cover recent publications in the last four years from January 2020 to December 2023. We will essentially focus on small molecule self-assembly, excluding polymer-based systems, which include various derivatives of monosaccharides, disaccharides, and oligosaccharides. Glycolipids, glycopeptides, and some glycoconjugate-based systems are discussed. Typically, in each category of systems, the system that can function as low molecular weight gelators (LMWGs) will be discussed first, followed by self-assembling systems that produce micelles and aggregates. The last section of the review discusses stimulus-responsive self-assembling systems, especially those forming gels, including dynamic covalent assemblies, chemical-triggered systems, and photoresponsive systems. The review will be organized based on the sugar structures, and in each category, the synthesis of representative molecular systems will be discussed next, followed by the properties of the resulting molecular assemblies.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430970","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}
Dong Xia, Yun Shi, Liying Jiang, Yang Li, Jianfei Kong
Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.
{"title":"Recent advances in the radical cascade reaction for constructing nitrogen heterocycles using azides as radical acceptors.","authors":"Dong Xia, Yun Shi, Liying Jiang, Yang Li, Jianfei Kong","doi":"10.1039/d4ob00732h","DOIUrl":"https://doi.org/10.1039/d4ob00732h","url":null,"abstract":"<p><p>Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430969","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}
Santosh J Gharpure, Deepika Kalita, Shipra Somani, Juhi Pal
Acid catalysed reductive etherification of N-propargyl amino alcohols for the stereoselective synthesis of cis-2,5/2,6-disubstituted morpholines and cis-2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines via a 6-exo-dig hydroalkoxylation-isomerization-reduction cascade. Interestingly, an alkyne hydration-cyclization-reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols. The strategy was used as a key step in the total synthesis of fungicides tridemorph and fenpropimorph.
{"title":"Deciphering substitution effects on reductive hydroalkoxylation of alkynyl aminols for stereoselective synthesis of morpholines and 1,4-oxazepanes: total synthesis of tridemorph and fenpropimorph.","authors":"Santosh J Gharpure, Deepika Kalita, Shipra Somani, Juhi Pal","doi":"10.1039/d4ob00855c","DOIUrl":"https://doi.org/10.1039/d4ob00855c","url":null,"abstract":"<p><p>Acid catalysed reductive etherification of <i>N</i>-propargyl amino alcohols for the stereoselective synthesis of <i>cis</i>-2,5/2,6-disubstituted morpholines and <i>cis</i>-2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines <i>via</i> a 6-<i>exo-dig</i> hydroalkoxylation-isomerization-reduction cascade. Interestingly, an alkyne hydration-cyclization-reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols. The strategy was used as a key step in the total synthesis of fungicides tridemorph and fenpropimorph.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430968","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 arene cyclopropanation between diazo compounds and benzene is well known to produce a tautomeric mixture of norcaradiene and cycloheptatriene in favour of the latter species. Nevertheless, previous studies have suggested that the initially formed norcaradiene can be stabilized by a C-7 cyano group with prevention of its 6π-electrocyclic ring opening. According to this feature, a synthetic route to functionalized cyclohexadienes has been designed using α-cyanodiazoacetates and α-diazo-β-ketonitriles as the starting materials, respectively. The Rh2(esp)2-catalyzed arene cyclopropanation of α-cyanodiazoacetates in benzene afforded the expected 7-alkoxycarbonyl-7-cyanonorcaradienes as isolable compounds, which then served as templates for the second cyclopropanation with ethyl diazoacetate or α-cyanodiazocarbonyls to enable the formation of bis(cyclopropanated) adducts. Their subsequent treatment with SmI2 triggered a double ring-opening process, allowing for the generation of 1,4- and/or 1,3-cyclohexadienes as either regio- or diastereomeric mixtures. On the other hand, the norcaradienes generated from phenyl- or methyl-substituted α-diazo-β-ketonitriles were found to undergo an in situ rearrangement to yield dihydrobenzofurans that could be converted to benzofuran derivatives by DDQ oxidation.
{"title":"Access to cyclohexadiene and benzofuran derivatives <i>via</i> catalytic arene cyclopropanation of α-cyanodiazocarbonyl compounds.","authors":"Mei-Lin Chen, Chi-Wen Chou, Jia-Liang Zhu, Ming-Hsuan Tsai","doi":"10.1039/d4ob00696h","DOIUrl":"https://doi.org/10.1039/d4ob00696h","url":null,"abstract":"<p><p>The arene cyclopropanation between diazo compounds and benzene is well known to produce a tautomeric mixture of norcaradiene and cycloheptatriene in favour of the latter species. Nevertheless, previous studies have suggested that the initially formed norcaradiene can be stabilized by a C-7 cyano group with prevention of its 6π-electrocyclic ring opening. According to this feature, a synthetic route to functionalized cyclohexadienes has been designed using α-cyanodiazoacetates and α-diazo-β-ketonitriles as the starting materials, respectively. The Rh<sub>2</sub>(esp)<sub>2</sub>-catalyzed arene cyclopropanation of α-cyanodiazoacetates in benzene afforded the expected 7-alkoxycarbonyl-7-cyanonorcaradienes as isolable compounds, which then served as templates for the second cyclopropanation with ethyl diazoacetate or α-cyanodiazocarbonyls to enable the formation of bis(cyclopropanated) adducts. Their subsequent treatment with SmI<sub>2</sub> triggered a double ring-opening process, allowing for the generation of 1,4- and/or 1,3-cyclohexadienes as either regio- or diastereomeric mixtures. On the other hand, the norcaradienes generated from phenyl- or methyl-substituted α-diazo-β-ketonitriles were found to undergo an <i>in situ</i> rearrangement to yield dihydrobenzofurans that could be converted to benzofuran derivatives by DDQ oxidation.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141430966","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}