An electrochemical approach with iodoarene as a mediator using recyclable ionic liquids to achieve dibromonative cyclization of 1,n-enynes has been reported. With recyclable bromine sources, in situ generation of iodine(III) compounds through electrochemical oxidation to achieve cyclization, a variety of heterocyclic frameworks containing both vinyl and alkyl bromide groups had been obtained in high yields with good selectivity.
{"title":"Electrochemical Oxidative Dibrominative Cyclization of 1,n-Enynes with Hypervalent Iodoarene Intermediates Utilizing Recyclable Bromine Ionic Liquids","authors":"Longji Li, Xu Wang, Huaibin Jiang, Yang’en You","doi":"10.1021/acs.joc.5c00049","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00049","url":null,"abstract":"An electrochemical approach with iodoarene as a mediator using recyclable ionic liquids to achieve dibromonative cyclization of 1,n-enynes has been reported. With recyclable bromine sources, <i>in situ</i> generation of iodine(III) compounds through electrochemical oxidation to achieve cyclization, a variety of heterocyclic frameworks containing both vinyl and alkyl bromide groups had been obtained in high yields with good selectivity.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"63 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Two unusual alkaloids with furanopyrrolidine skeleton, harzianopyrrolidones A–B (1–2), four new compounds, harzianopyridone B (3), harzianopyrone (4), (R)-1-(3,5-dihydroxy-4-methylphenyl)-1-hydroxyhept-5E-en-2-one (5), and harzianopyrrolidone C (6), together with two known compounds (7–8) were isolated from a marine-derived fungus Trichoderma harzianum ZN-4. Structures of the isolated compounds were elucidated based on their HRESIMS data, extensive NMR spectroscopic analyses, NMR calculation in combination with DP4+, ECD calculations, and a single-crystal X-ray diffraction experiment. New compounds 1, 4, and 5 exhibited potential cardiomyocyte protective activity at concentrations ranging from 5 to 20 μM. In addition, 7 showed moderate inhibitory activity against Pestalotiopsis theae with an MIC value of 25 μg/mL.
{"title":"Pyrrolidine Alkaloids and Polyketide Derivatives from the Marine-Derived Fungus Trichoderma harzianum ZN-4","authors":"Chengzeng Zhou, Xunuo Li, Jiayu Pan, Yichao Ge, Xiaodan Wu, Bin Wu","doi":"10.1021/acs.joc.4c03114","DOIUrl":"https://doi.org/10.1021/acs.joc.4c03114","url":null,"abstract":"Two unusual alkaloids with furanopyrrolidine skeleton, harzianopyrrolidones A–B (<b>1</b>–<b>2</b>), four new compounds, harzianopyridone B (<b>3</b>), harzianopyrone (<b>4</b>), (<i>R</i>)-1-(3,5-dihydroxy-4-methylphenyl)-1-hydroxyhept-5<i>E</i>-en-2-one (<b>5</b>), and harzianopyrrolidone C (<b>6</b>), together with two known compounds (<b>7</b>–<b>8</b>) were isolated from a marine-derived fungus <i>Trichoderma harzianum</i> ZN-4. Structures of the isolated compounds were elucidated based on their HRESIMS data, extensive NMR spectroscopic analyses, NMR calculation in combination with DP4+, ECD calculations, and a single-crystal X-ray diffraction experiment. New compounds <b>1</b>, <b>4,</b> and <b>5</b> exhibited potential cardiomyocyte protective activity at concentrations ranging from 5 to 20 μM. In addition, <b>7</b> showed moderate inhibitory activity against <i>Pestalotiopsis theae</i> with an MIC value of 25 μg/mL.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"23 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Radical-polar crossover (RPC) chemistry is an emerging field characterized by transformations that involve the coexistence of both radical and ionic species. Since the reactivities of radical and ionic intermediates are orthogonal, applying these two mechanisms in sequence provides significant advantages in the construction of complex molecular architectures. The concept of the RPC approach has become increasingly important in the total synthesis of natural products. This Synopsis presents several examples to showcase recent advancements in this area, including our research on the synthesis of Ganoderma meroterpenoids. In these selected cases, RPC reactions enhance the building of structural complexity and improve overall synthetic efficiency that cannot be achieved by standard synthetic methods.
{"title":"Natural Product Synthesis Enabled by Radical-Polar Crossover Reactions","authors":"Nicolas Müller, Thomas Magauer, Ondřej Kováč","doi":"10.1021/acs.joc.5c00306","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00306","url":null,"abstract":"Radical-polar crossover (RPC) chemistry is an emerging field characterized by transformations that involve the coexistence of both radical and ionic species. Since the reactivities of radical and ionic intermediates are orthogonal, applying these two mechanisms in sequence provides significant advantages in the construction of complex molecular architectures. The concept of the RPC approach has become increasingly important in the total synthesis of natural products. This Synopsis presents several examples to showcase recent advancements in this area, including our research on the synthesis of <i>Ganoderma</i> meroterpenoids. In these selected cases, RPC reactions enhance the building of structural complexity and improve overall synthetic efficiency that cannot be achieved by standard synthetic methods.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"216 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
An efficient method for the synthesis of the polycyclic molecules via cobalt-catalyzed [2 + 2 + 2] followed by [4 + 2] consecutive cycloaddition reaction strategy has been devised. Sequential cycloaddition reactions of substituted 1,6-diynes with maleimides have been performed. This tandem cycloaddition approach has yielded polyheterocyclic compounds exhibiting remarkable diastereoselectivity and achieving yields ranging from good to excellent. Additionally, a potential reaction mechanism has been proposed to explain the observed cycloaddition process.
{"title":"Cobalt(II)-Catalyzed [2 + 2 + 2]/[4 + 2] Cycloaddition of 1,6-Heptadiynes with Maleimides","authors":"Surenthiran Manickasundaram, Masilamani Jeganmohan","doi":"10.1021/acs.joc.4c02901","DOIUrl":"https://doi.org/10.1021/acs.joc.4c02901","url":null,"abstract":"An efficient method for the synthesis of the polycyclic molecules <i>via</i> cobalt-catalyzed [2 + 2 + 2] followed by [4 + 2] consecutive cycloaddition reaction strategy has been devised. Sequential cycloaddition reactions of substituted 1,6-diynes with maleimides have been performed. This tandem cycloaddition approach has yielded polyheterocyclic compounds exhibiting remarkable diastereoselectivity and achieving yields ranging from good to excellent. Additionally, a potential reaction mechanism has been proposed to explain the observed cycloaddition process.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"24 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deuterated aryl amines are increasingly sought after in pharmaceuticals, particularly in the development of deuterated drugs. Traditional methods for their synthesis often involve harsh conditions or preprepared reagents. This study introduces a mild, metal-free method for the selective deuteration of aryl amines, utilizing deuterium oxide (D2O) and a commercially available catalyst, tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBArF4). The reaction is performed under moderate conditions and is compatible with a wide range of substrates, including sensitive functional groups. Mechanistic studies highlight the crucial role of noncoordinated Na+ in catalysis, underscoring the broader potential of NaBArF4 and weakly coordinating anions (WCAs) in synthetic chemistry. This method offers an efficient and sustainable approach to synthesizing deuterated aryl amines.
{"title":"Easily Handled NaBArF4 Catalyzed Selective Electrophilic Deuteration Method for C(sp2)–H Bond of Aryl Amines","authors":"Jiahao Wu, Xiangwen Tan, Wanqing Wu, Huanfeng Jiang","doi":"10.1021/acs.joc.5c00066","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00066","url":null,"abstract":"Deuterated aryl amines are increasingly sought after in pharmaceuticals, particularly in the development of deuterated drugs. Traditional methods for their synthesis often involve harsh conditions or preprepared reagents. This study introduces a mild, metal-free method for the selective deuteration of aryl amines, utilizing deuterium oxide (D<sub>2</sub>O) and a commercially available catalyst, tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (NaBAr<sup>F</sup><sub>4</sub>). The reaction is performed under moderate conditions and is compatible with a wide range of substrates, including sensitive functional groups. Mechanistic studies highlight the crucial role of noncoordinated Na<sup>+</sup> in catalysis, underscoring the broader potential of NaBAr<sup>F</sup><sub>4</sub> and weakly coordinating anions (WCAs) in synthetic chemistry. This method offers an efficient and sustainable approach to synthesizing deuterated aryl amines.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"73 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We incorporated the hetero atoms (O/S) at the ortho-position to investigate the steric influence on controlling the rotational barrier around the C–N chiral axis and to elucidate the chiral attributes of sulfur-containing N-aryl peptoids. This study reports the simultaneous installation of a C–N chiral axis and the integration of sulfur-containing stereogenic elements in peptoid atropisomeric foldamers. By leveraging multiple chiral elements in peptoids, we demonstrated subtle structural variations, particularly by varying the sulfur oxidation states, that can lead to significant differences in the rotational energy barrier, as determined by dynamic HPLC. Additionally, we employed single-crystal X-ray crystallography to elucidate local conformational ordering and computational studies to identify noncovalent interactions in this class of atropisomers. Through these combined approaches, we explored sulfur-controlled modulation of N-aryl peptoid atropisomeric foldamers.
{"title":"Sulfur-Controlled Modulation of Peptoid Atropisomeric Foldamers","authors":"Nithin Kumara Mothahalli Raju, Bishwajit Paul, Lohith TN, Sandeep Bodduna, Nagesh Kumar Kandukuri","doi":"10.1021/acs.joc.4c02504","DOIUrl":"https://doi.org/10.1021/acs.joc.4c02504","url":null,"abstract":"We incorporated the hetero atoms (O/S) at the ortho-position to investigate the steric influence on controlling the rotational barrier around the C–N chiral axis and to elucidate the chiral attributes of sulfur-containing <i>N</i>-aryl peptoids. This study reports the simultaneous installation of a C–N chiral axis and the integration of sulfur-containing stereogenic elements in peptoid atropisomeric foldamers. By leveraging multiple chiral elements in peptoids, we demonstrated subtle structural variations, particularly by varying the sulfur oxidation states, that can lead to significant differences in the rotational energy barrier, as determined by dynamic HPLC. Additionally, we employed single-crystal X-ray crystallography to elucidate local conformational ordering and computational studies to identify noncovalent interactions in this class of atropisomers. Through these combined approaches, we explored sulfur-controlled modulation of <i>N</i>-aryl peptoid atropisomeric foldamers.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"29 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of efficient catalysts plays a central role in advancing chemical reactions. In this study, a ruthenium complex modified with a N-heterocyclic carbene-imine-phosphine ligand (CNP) was employed to enhance the hydrogen transfer/annulation process of 2-nitrobenzyl alcohols with various primary or secondary alcohols. The NMR and HRMS analyses of the reaction solution revealed the in situ formation of [fac-RuH(CO)(PPh3)(κ3-CN(H)P)]Cl through the transfer hydrogenation of the imine moiety within the CNP ligand under the reaction conditions. This species, a bifunctional Noyori-type ruthenium complex featuring facial coordination with a CN(H)P ligand, served as a key catalytic intermediate. By leveraging the outer-sphere mechanism facilitated by [fac-RuH(CO)(PPh3)(κ3-CN(H)P)]Cl, the synthesis of 75 quinolines from 2-nitrobenzyl alcohols and a wide range of alcohols has been achieved with yields as high as 95%.
{"title":"Ru-CNP Complex-Catalyzed Hydrogen Transfer/Annulation Reaction of 2-Nitrobenzylalcohol via an Outer-Sphere Mechanism","authors":"Ling Zhao, Yinyin Chen, Chunchun Zhang, Hua Chen, Xueli Zheng, Weichao Xue, Jiaqi Xu, Haiyan Fu, Ruixiang Li","doi":"10.1021/acs.joc.5c00157","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00157","url":null,"abstract":"The development of efficient catalysts plays a central role in advancing chemical reactions. In this study, a ruthenium complex modified with a <i>N</i>-heterocyclic carbene-imine-phosphine ligand <b>(CNP)</b> was employed to enhance the hydrogen transfer/annulation process of 2-nitrobenzyl alcohols with various primary or secondary alcohols. The NMR and HRMS analyses of the reaction solution revealed the in situ formation of [fac-RuH(CO)(PPh<sub>3</sub>)(κ<sup>3</sup>-CN(H)P)]Cl through the transfer hydrogenation of the imine moiety within the <b>CNP</b> ligand under the reaction conditions. This species, a bifunctional Noyori-type ruthenium complex featuring facial coordination with a <b>CN(H)P</b> ligand, served as a key catalytic intermediate. By leveraging the outer-sphere mechanism facilitated by [fac-RuH(CO)(PPh<sub>3</sub>)(κ<sup>3</sup>-CN(H)P)]Cl, the synthesis of 75 quinolines from 2-nitrobenzyl alcohols and a wide range of alcohols has been achieved with yields as high as 95%.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"60 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alkyne-equivalent dienophiles are strategically important coupling partners in Diels–Alder reactions. They are particularly useful in cascade bond-forming processes that begin with cycloadditions. A systematic rate study for the cycloaddition of several alkyne and alkyne-equivalent dienophiles is presented, showing that the relative reaction rates of these dienophiles vary over multiple orders of magnitude.
{"title":"Relative Cycloaddition Rates of Alkyne-Equivalent Dienophiles","authors":"Tucker J. Hamilton, Christopher M. Beaudry","doi":"10.1021/acs.joc.4c03028","DOIUrl":"https://doi.org/10.1021/acs.joc.4c03028","url":null,"abstract":"Alkyne-equivalent dienophiles are strategically important coupling partners in Diels–Alder reactions. They are particularly useful in cascade bond-forming processes that begin with cycloadditions. A systematic rate study for the cycloaddition of several alkyne and alkyne-equivalent dienophiles is presented, showing that the relative reaction rates of these dienophiles vary over multiple orders of magnitude.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"73 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiang Nan, Hanqing Zhang, Lanxin Zhu, Shilei Liu, Qiang Yan
A divergent [5 + 1] cyclization reaction of o-aminobenzamides with vinylene carbonate has been developed, rapidly generating three types of cyclic molecules including quinazolinones, 2-methylquinazolinones, and 2,3-dihydroquinazolinones with high chemoselectivity. In this discovery, vinylene carbonate blooms as a multifunctional reagent to participate in cyclization. The potential of this new finding is further emphasized by assembling the benzothiazole heteroarene via the [4 + 1] version and tolerating bioactive units well.
{"title":"Divergent [5 + 1] Annulation of o-Aminobenzamides with Vinylene Carbonate as a Multifunctional Reagent","authors":"Jiang Nan, Hanqing Zhang, Lanxin Zhu, Shilei Liu, Qiang Yan","doi":"10.1021/acs.joc.5c00039","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00039","url":null,"abstract":"A divergent [5 + 1] cyclization reaction of <i>o</i>-aminobenzamides with vinylene carbonate has been developed, rapidly generating three types of cyclic molecules including quinazolinones, 2-methylquinazolinones, and 2,3-dihydroquinazolinones with high chemoselectivity. In this discovery, vinylene carbonate blooms as a multifunctional reagent to participate in cyclization. The potential of this new finding is further emphasized by assembling the benzothiazole heteroarene via the [4 + 1] version and tolerating bioactive units well.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"18 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asmaa Habib, Estela Sánchez-Santos, Irene Boya del Teso, José J. Garrido-González, Francisca Sanz, Luis Simón, Joaquín R. Morán, Ángel L. Fuentes de Arriba
The steric strain between nitro and carboxylic acid groups in an 8-nitro-1-naphthoic acid derivative is able to unexpectedly disrupt the aromaticity of the naphthalene core under mild reaction conditions. The addition of H2O to the aromatic ring of a highly strained naphtho oxazinium intermediate induces the fragmentation of a Csp2–Csp2 bond, with a concomitant rearrangement to yield a conjugated aldehyde. Key intermediates have been characterized, and the X-ray structure of the derivative has been obtained. Density functional theory (DFT) studies were performed to confirm the proposed mechanism.
{"title":"Unusual Rearrangement of a 1,8-Naphthalene Derivative","authors":"Asmaa Habib, Estela Sánchez-Santos, Irene Boya del Teso, José J. Garrido-González, Francisca Sanz, Luis Simón, Joaquín R. Morán, Ángel L. Fuentes de Arriba","doi":"10.1021/acs.joc.5c00021","DOIUrl":"https://doi.org/10.1021/acs.joc.5c00021","url":null,"abstract":"The steric strain between nitro and carboxylic acid groups in an 8-nitro-1-naphthoic acid derivative is able to unexpectedly disrupt the aromaticity of the naphthalene core under mild reaction conditions. The addition of H<sub>2</sub>O to the aromatic ring of a highly strained naphtho oxazinium intermediate induces the fragmentation of a Csp<sup>2</sup>–Csp<sup>2</sup> bond, with a concomitant rearrangement to yield a conjugated aldehyde. Key intermediates have been characterized, and the X-ray structure of the derivative has been obtained. Density functional theory (DFT) studies were performed to confirm the proposed mechanism.","PeriodicalId":57,"journal":{"name":"Journal of Organic Chemistry","volume":"41 1","pages":""},"PeriodicalIF":4.354,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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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