Maude Cloutier, Nitish Verma, Ilona Douchez, Charles Gauthier
The synthesis of disaccharide mimics of Campylobacter jejuni HS:4c capsular polysaccharide, a major pathogen associated with campylobacteriosis, is challenged by the presence of a 1,2‐ cis ‐β‐linked 6‐deoxy‐ d ‐ ido ‐heptopyranoside. Herein, the development of a synthetic route to orthogonally protected d ‐ ido ‐hexo‐ and 6‐deoxy‐ d ‐ ido ‐heptopyranosyl donors is reported bearing diverse anomeric leaving groups, which represents, to the best of knowledge, the second direct access to 6‐deoxy‐ d ‐ ido ‐heptopyranosides from ido ‐configured precursors. These donors were evaluated in intramolecular aglycon delivery (IAD) and intermolecular glycosylation protocols. While IAD enabled complete β‐stereoselectivity with hexosyl donors, it failed with the heptosyl analog. Intermolecular glycosylation provided mixtures of anomers, but the use of a 7‐ O ‐acetyl‐protected heptosyl donor allowed access to the disaccharide in good yield, with chromatographic separation of the α‐ and β‐anomers. Structural analysis revealed unexpected conformational behavior, with the α‐disaccharide adopting the 1C4 chair conformation. This work establishes a foundation for the synthesis of C. jejuni HS:4c disaccharides and represents a step toward well‐defined sugar‐based vaccines candidates against campylobacteriosis.
空肠弯曲杆菌HS:4c荚膜多糖是一种与弯曲菌病相关的主要病原体，其双糖模拟物的合成受到1,2‐cis‐β‐连接的6‐脱氧‐d‐ido‐heptopyranoside存在的挑战。本文报道了一种具有正交保护的d - ido -己基和6 -脱氧- d - ido -庚基供体的合成途径的发展，这些供体具有不同的端粒离去基，据我们所知，这代表了从ido -构型前体中直接获得6 -脱氧- d - ido -庚基苷的第二种途径。这些供体在分子内糖基传递（IAD）和分子间糖基化方案中进行评估。虽然IAD对己糖基供体具有完全的β -立体选择性，但对庚糖基类似物不起作用。分子间糖基化提供了异头化合物的混合物，但使用7‐O‐乙酰基保护的庚基供体可以通过色谱分离α‐和β‐异头化合物，从而获得高产量的双糖。结构分析揭示了意想不到的构象行为，α‐双糖采用1 c4椅构象。这项工作为空肠梭菌HS:4c双糖的合成奠定了基础，并代表着朝着明确定义的以糖为基础的抗弯曲杆菌病候选疫苗迈出了一步。
{"title":"Intra‐ and Intermolecular Glycosylation of d ‐Idopyranosyl and 6‐Deoxy‐ d ‐ ido ‐heptopyranosyl Donors: Toward the Repeating Unit of Campylobacter jejuni HS:4c Capsular Polysaccharide","authors":"Maude Cloutier, Nitish Verma, Ilona Douchez, Charles Gauthier","doi":"10.1002/ejoc.202500894","DOIUrl":"https://doi.org/10.1002/ejoc.202500894","url":null,"abstract":"The synthesis of disaccharide mimics of <jats:italic>Campylobacter jejuni</jats:italic> HS:4c capsular polysaccharide, a major pathogen associated with campylobacteriosis, is challenged by the presence of a 1,2‐ <jats:italic>cis</jats:italic> ‐β‐linked 6‐deoxy‐ <jats:sc>d</jats:sc> ‐ <jats:italic>ido</jats:italic> ‐heptopyranoside. Herein, the development of a synthetic route to orthogonally protected <jats:sc>d</jats:sc> ‐ <jats:italic>ido</jats:italic> ‐hexo‐ and 6‐deoxy‐ <jats:sc>d</jats:sc> ‐ <jats:italic>ido</jats:italic> ‐heptopyranosyl donors is reported bearing diverse anomeric leaving groups, which represents, to the best of knowledge, the second direct access to 6‐deoxy‐ <jats:sc>d</jats:sc> ‐ <jats:italic>ido</jats:italic> ‐heptopyranosides from <jats:italic>ido</jats:italic> ‐configured precursors. These donors were evaluated in intramolecular aglycon delivery (IAD) and intermolecular glycosylation protocols. While IAD enabled complete β‐stereoselectivity with hexosyl donors, it failed with the heptosyl analog. Intermolecular glycosylation provided mixtures of anomers, but the use of a 7‐ <jats:italic>O</jats:italic> ‐acetyl‐protected heptosyl donor allowed access to the disaccharide in good yield, with chromatographic separation of the α‐ and β‐anomers. Structural analysis revealed unexpected conformational behavior, with the α‐disaccharide adopting the <jats:sup>1</jats:sup> <jats:italic>C</jats:italic> <jats:sub>4</jats:sub> chair conformation. This work establishes a foundation for the synthesis of <jats:italic>C. jejuni</jats:italic> HS:4c disaccharides and represents a step toward well‐defined sugar‐based vaccines candidates against campylobacteriosis.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"38 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718392","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}
Wei Zhao, Sining Wang, Haixing Xu, Kun Zhao, Tao Shu
Herein, we described an efficient gold(I)‐catalyzed redox cycloisomerization/[3+2] dipolar cycloaddition domino reaction of o ‐(alkynyl)nitrobenzenes. The domino process involves the in situ generation of α‐oxo gold carbenes via intramolecular redox reactions of alkynes and nitro functional groups, followed by the formation of nitrones and subsequent intramolecular [3+2] dipolar cycloaddition reaction to furnish a diverse array of complex isoxazolidine‐containing polycyclic scaffolds in moderate to good yields, with up to excellent diastereoselectivities.
{"title":"Gold‐Catalyzed Redox Cycloisomerization/[3+2] Dipolar Cycloaddition Domino Reactions: Construction of Isoxazolidine‐Containing Polycyclic Scaffolds","authors":"Wei Zhao, Sining Wang, Haixing Xu, Kun Zhao, Tao Shu","doi":"10.1002/ejoc.202501012","DOIUrl":"https://doi.org/10.1002/ejoc.202501012","url":null,"abstract":"Herein, we described an efficient gold(I)‐catalyzed redox cycloisomerization/[3+2] dipolar cycloaddition domino reaction of <jats:italic>o</jats:italic> ‐(alkynyl)nitrobenzenes. The domino process involves the in situ generation of α‐oxo gold carbenes via intramolecular redox reactions of alkynes and nitro functional groups, followed by the formation of nitrones and subsequent intramolecular [3+2] dipolar cycloaddition reaction to furnish a diverse array of complex isoxazolidine‐containing polycyclic scaffolds in moderate to good yields, with up to excellent diastereoselectivities.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"2 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145718393","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, a continuous photo‐flow protocol for quinolinamide‐directed regioselective C‐8 benzylation of 1‐naphthylamine derivatives via CH bond functionalization with flow‐generated aryldiazomethanes is reported. A wide range of 8‐benzylated‐1‐naphthylamide products are afforded in satisfactory yields upon palladium catalysis via a bidentate directing process under illumination by 12 W blue light‐emitting diodes (450 nm). This mild, simple, and convenient synthetic method allows a wide range of easily handled aryl aldehydes, without the exclusion of either moisture or oxygen. This transformation is environmentally friendly and operationally simple, and it can be easily scaled up to the gram scale with good selectivity. Finally, an improved protocol for CH functionalization is described, which relies on the use of a continuous‐flow photo‐microreactor.
{"title":"Blue‐Light‐Induced Pd‐Catalyzed Quinolinamide‐Directed Regioselective C‐8 Benzylation of 1‐Naphthylamines Using Flow‐Generated Aryldiazomethanes in Batch and Continuous‐Flow","authors":"Wei Zhang , Yanxin Xie , Zaikun Xue , Changqing Miao , Jiao Guo , Baoli Zhao","doi":"10.1002/ejoc.202500849","DOIUrl":"10.1002/ejoc.202500849","url":null,"abstract":"<div><div>Herein, a continuous photo‐flow protocol for quinolinamide‐directed regioselective C‐8 benzylation of 1‐naphthylamine derivatives via CH bond functionalization with flow‐generated aryldiazomethanes is reported. A wide range of 8‐benzylated‐1‐naphthylamide products are afforded in satisfactory yields upon palladium catalysis via a bidentate directing process under illumination by 12 W blue light‐emitting diodes (450 nm). This mild, simple, and convenient synthetic method allows a wide range of easily handled aryl aldehydes, without the exclusion of either moisture or oxygen. This transformation is environmentally friendly and operationally simple, and it can be easily scaled up to the gram scale with good selectivity. Finally, an improved protocol for CH functionalization is described, which relies on the use of a continuous‐flow photo‐microreactor.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500849"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145288669","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 salt‐free CatAnionic vesicle is previously generated by mixing cationic and anionic amphiphiles and removing the salt that occurred as a byproduct from the mixture. In this study, a new strategy to produce the salt‐free CatAnionic vesicle of N,N‐dialkylammonium N,N‐dialkyldithiocarbamate (AmDTC) is reported through a one‐step condensation between secondary amine and CS2. The AmDTC dispersed in water, resulting in the spontaneous formation of salt‐free CatAnionic vesicles. Among several AmDTCs, the N,N‐didodecylammonium N,N‐didodecyldithiocarbamate (AmDTC‐C12) showed high stability and is applied as a vesicular nanoreactor for the Michael addition in water. These vesicles catalyzed aqueous Michael additions of nitroolefins, affording 23 adducts in 65%–92% yields. The vesicles enabled preparative‐scale and one‐pot Michael addition by in situ generation of AmDTC‐C12 vesicle afforded the Michael adducts also in good yields. The AmDTC‐C12 vesicular nanoreactor is applied for the synthesis of (±)‐baclofen with 54% yields over three steps. Reusability of the AmDTC‐C12 is demonstrated and allowed the reuse up to seven cycles. Finally, chemical recycling of N,N‐didodecylamine precursor is demonstrated by converting AmDTC‐C12 to N,N‐didodecylammonium chloride salt by simple acidification. Owing to their simple precursors and mild synthesis, salt‐free CatAnionic vesicles from AmDTC show promising and untapped potentials as organocatalysts and delivery applications.
无盐的cat阴离子囊泡是通过混合阳离子和阴离子两亲体并去除混合物中作为副产物的盐而产生的。本文报道了一种通过仲胺与cs2一步缩合制备N， N -二烷基二硫代氨基甲酸铵（AmDTC）无盐阳离子囊泡的新策略。AmDTC分散在水中，导致自发形成无盐的catanonic囊泡。在几种AmDTC中，N， N -二十二烷基铵N， N -二十二烷基二硫代氨基甲酸酯（AmDTC - C12）表现出较高的稳定性，并作为囊状纳米反应器应用于水中的Michael加成。这些囊泡催化了硝基烯烃的水溶液加成，得到23种加合物，产率为65% ~ 92%。通过原位生成AmDTC - C12囊泡，该囊泡实现了制备规模和一锅Michael加成，也获得了高产量的Michael加合物。AmDTC - C12囊状纳米反应器用于合成（±）-巴氯芬，三步合成收率为54%。演示了AmDTC - C12的可重用性，并允许重复使用多达七个周期。最后，通过简单酸化将AmDTC - C12转化为N， N‐二十二烷基氯化铵盐，证明了N， N‐二十二烷基胺前体的化学回收。由于其简单的前体和温和的合成，来自AmDTC的无盐cat阴离子囊泡作为有机催化剂和递送应用具有广阔的潜力。
{"title":"Salt‐Free CatAnionic Vesicular Nanoreactor from Dithiocarbamate: Michael Addition of Nitroolefins in Water","authors":"Panassilp Authai , Witsanu Sombat , Voravee P. Hoven , Tirayut Vilaivan , Panuwat Padungros","doi":"10.1002/ejoc.202500770","DOIUrl":"10.1002/ejoc.202500770","url":null,"abstract":"<div><div>The salt‐free CatAnionic vesicle is previously generated by mixing cationic and anionic amphiphiles and removing the salt that occurred as a byproduct from the mixture. In this study, a new strategy to produce the salt‐free CatAnionic vesicle of <em>N</em>,<em>N</em>‐dialkylammonium <em>N</em>,<em>N</em>‐dialkyldithiocarbamate (AmDTC) is reported through a one‐step condensation between secondary amine and CS<sub>2</sub>. The AmDTC dispersed in water, resulting in the spontaneous formation of salt‐free CatAnionic vesicles. Among several AmDTCs, the <em>N</em>,<em>N</em>‐didodecylammonium <em>N</em>,<em>N</em>‐didodecyldithiocarbamate (<strong>AmDTC‐C12</strong>) showed high stability and is applied as a vesicular nanoreactor for the Michael addition in water. These vesicles catalyzed aqueous Michael additions of nitroolefins, affording 23 adducts in 65%–92% yields. The vesicles enabled preparative‐scale and one‐pot Michael addition by in situ generation of <strong>AmDTC‐C12</strong> vesicle afforded the Michael adducts also in good yields. The <strong>AmDTC‐C12</strong> vesicular nanoreactor is applied for the synthesis of (±)‐baclofen with 54% yields over three steps. Reusability of the <strong>AmDTC‐C12</strong> is demonstrated and allowed the reuse up to seven cycles. Finally, chemical recycling of <em>N</em>,<em>N</em>‐didodecylamine precursor is demonstrated by converting <strong>AmDTC‐C12</strong> to <em>N</em>,<em>N</em>‐didodecylammonium chloride salt by simple acidification. Owing to their simple precursors and mild synthesis, salt‐free CatAnionic vesicles from AmDTC show promising and untapped potentials as organocatalysts and delivery applications.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500770"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381823","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}
Binbin Fei , Yangzilin Kong , Yanan Liu , Ni Gu , Qiang Tang , Yongjia Shang , Xinwei He
A novel three‐component van Leusen strategy has been developed for the efficient and straightforward synthesis of valuable 3,4‐disubstituted pyrroles from easily available propargylamines, tosylmethyl isocyanide, and water. This transformation advances through the formation of a pyrrole framework via [3 + 2] cycloaddition with tosylmethyl isocyanide and a sequential nucleophilic substitution, ring‐opening, and deprotonation/protonation cascade process. This reaction provides a convenient modular access to pyrrole derivatives with aryl and benzoyl groups through the formation of three new bonds and one heterocycle from readily available acyclic precursors in a single step.
{"title":"Modular Synthesis of 3,4‐Disubstituted Pyrroles Through Three‐Component Van Leusen Reaction of Propargylamines with Tosylmethyl Isocyanide and Water","authors":"Binbin Fei , Yangzilin Kong , Yanan Liu , Ni Gu , Qiang Tang , Yongjia Shang , Xinwei He","doi":"10.1002/ejoc.202500855","DOIUrl":"10.1002/ejoc.202500855","url":null,"abstract":"<div><div>A novel three‐component van Leusen strategy has been developed for the efficient and straightforward synthesis of valuable 3,4‐disubstituted pyrroles from easily available propargylamines, tosylmethyl isocyanide, and water. This transformation advances through the formation of a pyrrole framework via [3 + 2] cycloaddition with tosylmethyl isocyanide and a sequential nucleophilic substitution, ring‐opening, and deprotonation/protonation cascade process. This reaction provides a convenient modular access to pyrrole derivatives with aryl and benzoyl groups through the formation of three new bonds and one heterocycle from readily available acyclic precursors in a single step.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500855"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247212","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}
Fen Xu , Zi‐Han Wang , Meng‐Yu Sun , Luciano Barboni , Yuan Feng , Huan‐Huan Zhao , Yang Yang , Fan‐Wang Zeng
The development of one‐step transformations to heterocyclic compounds would considerably boost the synthetic efficiency in organic chemistry. In recent years, numerous examples of the transition‐metal‐catalyzed (TMC) CH activation/annulation strategy have been reported. Despite remarkable progress achieved with internal alkynes, allenes, and alkyne surrogates, terminal alkynes remain challenging substrates. Due to their relatively acidic terminal protons, terminal alkynes easily undergo alternative homocoupling reactions under commonly used oxidative conditions, exhibiting significant difficulties in CH functionalizations. To date, the CH activation involving terminal alkynes remains one of the most promising and appealing areas in organic synthesis. This review provides a comprehensive overview of the current progress in tandem CH activation reactions with terminal alkynes. With a strong emphasis on the catalysis of Rh and Co transition metals, it predominantly covers the synthesis of five‐, six‐membered heterocycles, and fused heterocycles. In this protocol, specific topics, such as purely chemical synthesis, electrochemical synthesis, and enantioselective synthesis, mechanistic details associated with the documented reactions are discussed. In addition, a tactical user guidance for terminal alkynes‐participated CH activation is also put forward.
{"title":"Transition‐Metal‐Catalyzed Convergent Synthesis of Heterocyclic Compounds via CH Activation/Cyclization: An Overview and Summary Toward Terminal Alkynes","authors":"Fen Xu , Zi‐Han Wang , Meng‐Yu Sun , Luciano Barboni , Yuan Feng , Huan‐Huan Zhao , Yang Yang , Fan‐Wang Zeng","doi":"10.1002/ejoc.202500651","DOIUrl":"10.1002/ejoc.202500651","url":null,"abstract":"<div><div>The development of one‐step transformations to heterocyclic compounds would considerably boost the synthetic efficiency in organic chemistry. In recent years, numerous examples of the transition‐metal‐catalyzed (TMC) CH activation/annulation strategy have been reported. Despite remarkable progress achieved with internal alkynes, allenes, and alkyne surrogates, terminal alkynes remain challenging substrates. Due to their relatively acidic terminal protons, terminal alkynes easily undergo alternative homocoupling reactions under commonly used oxidative conditions, exhibiting significant difficulties in CH functionalizations. To date, the CH activation involving terminal alkynes remains one of the most promising and appealing areas in organic synthesis. This review provides a comprehensive overview of the current progress in tandem CH activation reactions with terminal alkynes. With a strong emphasis on the catalysis of Rh and Co transition metals, it predominantly covers the synthesis of five‐, six‐membered heterocycles, and fused heterocycles. In this protocol, specific topics, such as purely chemical synthesis, electrochemical synthesis, and enantioselective synthesis, mechanistic details associated with the documented reactions are discussed. In addition, a tactical user guidance for terminal alkynes‐participated CH activation is also put forward.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500651"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145289249","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}
Pooja Sivaganesan , Ghanashyam Sivaprasad , Diksha Bansal , Mrinal Kanti Das , Saikat Chaudhuri
A mild, water‐mediated protocol has been developed for the synthesis of both uncyclized and cyclized 1,8‐dioxo‐octahydroxanthene derivatives under ambient conditions. Utilizing cyclic‐1,3‐dicarbonyl compounds and structurally diverse aromatic or heteroaromatic aldehydes, the transformation proceeds efficiently with cyanuric chloride (TCT) as a green organocatalyst. The reaction conditions are finely tunable, allowing selective access to either uncyclized intermediates or cyclized products by adjusting time and temperature, thereby enabling modular control over product outcomes. The protocol also demonstrates excellent compatibility with isatin derivatives, yielding spirooxindolo xanthenedione frameworks in high yields. Substrate scope evaluation revealed broad functional group tolerance, with several products displaying notable biological activities, including anticancer, antibacterial, and antileishmanial properties. All synthesized compounds are fully characterized using spectroscopic techniques such as 1H, 13C, and mass spectroscopy. A detailed, plausible mechanism for the transformation has also been proposed and discussed. Comprehensive green metrics, including atom economy, E‐factor, process mass intensity, and other metrics, are calculated for each cyclized derivative. Gram‐scale experiments further confirmed the scalability and environmental sustainability of this operationally simple, metal‐free, and energy‐efficient protocol.
{"title":"A Practical and Scalable Synthesis of Cyclized and Uncyclized Xanthene‐1,8‐Dione Derivatives Using Cyanuric Chloride as a Green Organocatalyst","authors":"Pooja Sivaganesan , Ghanashyam Sivaprasad , Diksha Bansal , Mrinal Kanti Das , Saikat Chaudhuri","doi":"10.1002/ejoc.202500921","DOIUrl":"10.1002/ejoc.202500921","url":null,"abstract":"<div><div>A mild, water‐mediated protocol has been developed for the synthesis of both uncyclized and cyclized 1,8‐dioxo‐octahydroxanthene derivatives under ambient conditions. Utilizing cyclic‐1,3‐dicarbonyl compounds and structurally diverse aromatic or heteroaromatic aldehydes, the transformation proceeds efficiently with cyanuric chloride (TCT) as a green organocatalyst. The reaction conditions are finely tunable, allowing selective access to either uncyclized intermediates or cyclized products by adjusting time and temperature, thereby enabling modular control over product outcomes. The protocol also demonstrates excellent compatibility with isatin derivatives, yielding spirooxindolo xanthenedione frameworks in high yields. Substrate scope evaluation revealed broad functional group tolerance, with several products displaying notable biological activities, including anticancer, antibacterial, and antileishmanial properties. All synthesized compounds are fully characterized using spectroscopic techniques such as <sup>1</sup>H, <sup>13</sup>C, and mass spectroscopy. A detailed, plausible mechanism for the transformation has also been proposed and discussed. Comprehensive green metrics, including atom economy, E‐factor, process mass intensity, and other metrics, are calculated for each cyclized derivative. Gram‐scale experiments further confirmed the scalability and environmental sustainability of this operationally simple, metal‐free, and energy‐efficient protocol.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500921"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145381825","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}
Isoquinoline compounds, especially 1‐substituted derivatives, have garnered considerable attention due to their ubiquitous presence in natural products and pharmaceuticals. Herein, a novel visible‐light‐induced tandem cyclization of vinyl isocyanides with diaryl disulfides or 1,2‐dialkyldiselanes has been developed. The reaction tolerates a wide range of substrates and provides an environmentally friendly route to the synthesis of 1‐thio/selenoisoquinolines from the easily available starting materials in a single step.
{"title":"Visible‐Light‐Induced Cyclization of Vinyl Isocyanides with Diaryl Disulfides/1,2‐Dialkyldiselanes for the Synthesis of 1‐Substituted Isoquinolines","authors":"Yong‐Xin Liang , Qing‐Wen Ai , Xue‐Cen Xu , Yu‐Long Zhao","doi":"10.1002/ejoc.202500715","DOIUrl":"10.1002/ejoc.202500715","url":null,"abstract":"<div><div>Isoquinoline compounds, especially 1‐substituted derivatives, have garnered considerable attention due to their ubiquitous presence in natural products and pharmaceuticals. Herein, a novel visible‐light‐induced tandem cyclization of vinyl isocyanides with diaryl disulfides or 1,2‐dialkyldiselanes has been developed. The reaction tolerates a wide range of substrates and provides an environmentally friendly route to the synthesis of 1‐thio/selenoisoquinolines from the easily available starting materials in a single step.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500715"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145246980","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, a straightforward approach is reported for the palladium‐catalyzed oxidative remote CH alkylation of 8‐aminoquinoline derivatives using para‐quinone methides. This method enables selective C5‐alkylation of quinolines and exhibits a site‐selectivity distinct from that typically observed in convetional palladium‐catalyzed sp2 CH activation. The reaction proceeds via chelation‐induced remote CH functionalization, and a broad range of quinolinamides are successfully coupled with p‐quinone methides, demonstrating excellent substrate scope and functional group tolerance. Preliminary mechanistic studies suggest a reversible CH metalation step as part of the catalytic cycle.
本文报道了一种用对醌方法催化8-氨基喹啉衍生物的钯催化氧化远端C - H烷基化的直接方法。该方法实现了喹啉的选择性c5烷基化，并表现出与传统钯催化的sp2 C - H活化不同的位点选择性。该反应通过螯合诱导的C - H远程官能团化进行，广泛的喹啉胺类化合物成功地与对醌类化合物偶联，表现出良好的底物范围和官能团耐受性。初步的机理研究表明，可逆的C - H金属化步骤是催化循环的一部分。
{"title":"Palladium(II)‐Catalyzed Distal CH Functionalization of 8‐Aminoquinolinamides: Facile Synthesis of Triarylmethane Derivatives","authors":"Anushka Rastogi , Mohit Kumar , Manoj Kumar Gangwar , Dipankar Koley","doi":"10.1002/ejoc.202500493","DOIUrl":"10.1002/ejoc.202500493","url":null,"abstract":"<div><div>Herein, a straightforward approach is reported for the palladium‐catalyzed oxidative remote CH alkylation of 8‐aminoquinoline derivatives using <em>para‐</em>quinone methides. This method enables selective C5‐alkylation of quinolines and exhibits a site‐selectivity distinct from that typically observed in convetional palladium‐catalyzed sp<sup>2</sup> CH activation. The reaction proceeds via chelation‐induced remote CH functionalization, and a broad range of quinolinamides are successfully coupled with <em>p</em>‐quinone methides, demonstrating excellent substrate scope and functional group tolerance. Preliminary mechanistic studies suggest a reversible CH metalation step as part of the catalytic cycle.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500493"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145247213","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}
Marek Surowiec , Ioannis E. Gerontitis , Petros G. Tsoungas , Panteleimon G. Takis , Panagiotis Stathopoulos , Erietta Pouliou , George Varvounis
[1,1′‐Binaphthalene]‐2,2′‐diol (BINOL) analog, [1,1′‐binaphthalene]‐4,4′‐diol, obtained by direct oxidative coupling of 1‐naphthol, is acylated to [1,1′‐binaphthalene]‐4,4′‐diyl diacetate and then rearranged by the Fries reaction to 1,1'‐{4,4'‐dihydroxy‐[1,1'‐binaphthalene]‐3,3'‐diyl}bis(ethan‐1‐one). Incorporation of aldehyde groups at the 3,3' positions of [1,1′‐binaphthalene]‐4,4′‐diol required oxidative coupling of 1‐methoxynaphthalene to 4,4′‐dimethoxy‐1,1′‐binaphthalene, bromination, formylation, and demethylation. Incorporation of benzoyl groups at the 3,3' positions of [1,1′‐binaphthalene]‐4,4′‐diol required subjecting either 1‐(4‐bromo‐1‐hydroxy‐2‐naphthyl)(phenyl)methanone to the Ullmann reaction conditions or 4,4′‐dimethoxy‐1,1′‐binaphthalene to the Friedel–Crafts reaction with benzoyl chloride. The 1,1′‐(4,4′‐dihydroxy‐1,1′‐binaphthalene‐3,3′‐diyl)dicarbonyls are converted to the corresponding dioximes, which then underwent cyclodehydration to the respective novel 5,5'‐binaphtho[2,1‐d]isoxazoles.
{"title":"Synthesis of Novel BINOL Analogs: 3,3′‐Dicarbonyl‐1,1′‐binaphthyl‐4,4′‐diols as Precursors to the Uncharted 5,5′‐Binaphtho[2,1‐d]isoxazole","authors":"Marek Surowiec , Ioannis E. Gerontitis , Petros G. Tsoungas , Panteleimon G. Takis , Panagiotis Stathopoulos , Erietta Pouliou , George Varvounis","doi":"10.1002/ejoc.202500681","DOIUrl":"10.1002/ejoc.202500681","url":null,"abstract":"<div><div>[1,1′‐Binaphthalene]‐2,2′‐diol (BINOL) analog, [1,1′‐binaphthalene]‐4,4′‐diol, obtained by direct oxidative coupling of 1‐naphthol, is acylated to [1,1′‐binaphthalene]‐4,4′‐diyl diacetate and then rearranged by the Fries reaction to 1,1<em>'</em>‐{4,4<em>'</em>‐dihydroxy‐[1,1<em>'</em>‐binaphthalene]‐3,3<em>'</em>‐diyl}bis(ethan‐1‐one). Incorporation of aldehyde groups at the 3,3<em>'</em> positions of [1,1′‐binaphthalene]‐4,4′‐diol required oxidative coupling of 1‐methoxynaphthalene to 4,4′‐dimethoxy‐1,1′‐binaphthalene, bromination, formylation, and demethylation. Incorporation of benzoyl groups at the 3,3<em>'</em> positions of [1,1′‐binaphthalene]‐4,4′‐diol required subjecting either 1‐(4‐bromo‐1‐hydroxy‐2‐naphthyl)(phenyl)methanone to the Ullmann reaction conditions or 4,4′‐dimethoxy‐1,1′‐binaphthalene to the Friedel–Crafts reaction with benzoyl chloride. The 1,1′‐(4,4′‐dihydroxy‐1,1′‐binaphthalene‐3,3′‐diyl)dicarbonyls are converted to the corresponding dioximes, which then underwent cyclodehydration to the respective novel 5,5<em>'</em>‐binaphtho[2,1‐<em>d</em>]isoxazoles.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 45","pages":"Article e202500681"},"PeriodicalIF":2.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145282965","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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