Jordan LEHOUX, Felix GROSJEAN, Alexandre LOBO, Michel LAGARDE, Nathalie Bernoud-Hubac, Thierry DURAND, Céline CRAUSTE
Docosahexaenoic acid (DHA, C22:6 n‐3) is a critical omega‐3 polyunsaturated fatty acid (PUFA) with essential roles in brain and retinal functions. Its selective uptake into these tissues is mediated by several pathways, including the transporter Mfsd2a, which preferentially utilizes lysophosphatidylcholine‐DHA (LPC‐DHA) as a substrate. Due to the low de novo synthesis of DHA, optimizing its dietary intake and exploring novel delivery strategies are important in pathologies that affect PUFA proportion. The present work focuses on developing an efficient chemo‐enzymatic methodology to access structured mixed DHA phosphatidylcholines (mixed DHA‐PCs), valuable biological tools for enhancing drug and/or DHA delivery to the brain and retina. Chemo‐enzymatic methods were established to synthesize mixed sn1‐ or sn2‐DHA‐PC isomers, to study the importance of DHA position, from cost‐effective glycerophosphorylcholine (GPC). The approach aligns with green chemistry principles by leveraging lipase‐catalyzed regioselective acylation and deacylation reactions, thus reducing the number of chemical steps compared to traditional methods. The resulting mixed PCs AceDoPC®, DoAcePC (stabilized forms of LPC‐DHA), and phenolic‐DHA‐PCs were produced at a scale suitable for future in vivo studies, enabling investigations into the positional effect of DHA on brain and retinal uptake.
{"title":"Chemo‐Enzymatic Synthesis of Mixed Docosahexaenoic Acid Phosphatidylcholine Conjugates","authors":"Jordan LEHOUX, Felix GROSJEAN, Alexandre LOBO, Michel LAGARDE, Nathalie Bernoud-Hubac, Thierry DURAND, Céline CRAUSTE","doi":"10.1002/ejoc.202500083","DOIUrl":"https://doi.org/10.1002/ejoc.202500083","url":null,"abstract":"Docosahexaenoic acid (DHA, C22:6 n‐3) is a critical omega‐3 polyunsaturated fatty acid (PUFA) with essential roles in brain and retinal functions. Its selective uptake into these tissues is mediated by several pathways, including the transporter Mfsd2a, which preferentially utilizes lysophosphatidylcholine‐DHA (LPC‐DHA) as a substrate. Due to the low de novo synthesis of DHA, optimizing its dietary intake and exploring novel delivery strategies are important in pathologies that affect PUFA proportion. The present work focuses on developing an efficient chemo‐enzymatic methodology to access structured mixed DHA phosphatidylcholines (mixed DHA‐PCs), valuable biological tools for enhancing drug and/or DHA delivery to the brain and retina. Chemo‐enzymatic methods were established to synthesize mixed sn1‐ or sn2‐DHA‐PC isomers, to study the importance of DHA position, from cost‐effective glycerophosphorylcholine (GPC). The approach aligns with green chemistry principles by leveraging lipase‐catalyzed regioselective acylation and deacylation reactions, thus reducing the number of chemical steps compared to traditional methods. The resulting mixed PCs AceDoPC®, DoAcePC (stabilized forms of LPC‐DHA), and phenolic‐DHA‐PCs were produced at a scale suitable for future in vivo studies, enabling investigations into the positional effect of DHA on brain and retinal uptake.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"16 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435405","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}
Mohamed Ali Dridi, Mohamed Hasyeoui, Frédéric Lassagne, William Erb, Charline Piroud, Thomas Robert, Stéphane Bach, Ali Samarat, Soufiane Touil, Florence Mongin
Despite their potential in areas such as medicinal chemistry and organic materials, scaffolds in which quinoline and quinoxaline are fused to phosphacycles such as 1,3-oxaphosphole, 1,3-azaphosphole, P-arylated and P-alkoxylated 2,3-dihydro-1,3-azaphosphole P-oxides have, to our knowledge, never been reported. In this study we have developed a synthetic approach to [1,3]azaphospholo[4,5-f]quinolines and -quinoxalines from quinolin-6-amine and quinoxalin-6-amine. These were converted to 5-phosphanylquino(xa)lin-6-amines by regioselective iodination in position 5, cross-coupling with diethyl phosphite and reduction. Formation of the azaphosphole ring was then achieved by reaction with N,N-dimethylformamide dimethyl acetal. Attempts at C-H arylation in position 2 did not lead to the desired derivatives but rather to 1-arylated 2,3-dihydro-[1,3]azaphospholo[4,5-f]quino(xa)line 1-oxides. Access to 1-alkoxylated 2,3-dihydro-[1,3]azaphospholo[4,5-f]quinoline 1-oxides was also developed using as key steps cross-coupling with ethyl phosphinate formed in situ and the subsequent Kabachnik-Fields reaction. The resulting tricyclic compounds were finally tested against a panel of disease-related protein kinases.
{"title":"On the Synthesis of [1,3]Azaphospholo[4,5-f]quino(xa)lines and 2,3-Dihydro-[1,3]azaphospholo[4,5-f]quino(xa)line 1-oxides","authors":"Mohamed Ali Dridi, Mohamed Hasyeoui, Frédéric Lassagne, William Erb, Charline Piroud, Thomas Robert, Stéphane Bach, Ali Samarat, Soufiane Touil, Florence Mongin","doi":"10.1002/ejoc.202500080","DOIUrl":"https://doi.org/10.1002/ejoc.202500080","url":null,"abstract":"Despite their potential in areas such as medicinal chemistry and organic materials, scaffolds in which quinoline and quinoxaline are fused to phosphacycles such as 1,3-oxaphosphole, 1,3-azaphosphole, P-arylated and P-alkoxylated 2,3-dihydro-1,3-azaphosphole P-oxides have, to our knowledge, never been reported. In this study we have developed a synthetic approach to [1,3]azaphospholo[4,5-f]quinolines and -quinoxalines from quinolin-6-amine and quinoxalin-6-amine. These were converted to 5-phosphanylquino(xa)lin-6-amines by regioselective iodination in position 5, cross-coupling with diethyl phosphite and reduction. Formation of the azaphosphole ring was then achieved by reaction with N,N-dimethylformamide dimethyl acetal. Attempts at C-H arylation in position 2 did not lead to the desired derivatives but rather to 1-arylated 2,3-dihydro-[1,3]azaphospholo[4,5-f]quino(xa)line 1-oxides. Access to 1-alkoxylated 2,3-dihydro-[1,3]azaphospholo[4,5-f]quinoline 1-oxides was also developed using as key steps cross-coupling with ethyl phosphinate formed in situ and the subsequent Kabachnik-Fields reaction. The resulting tricyclic compounds were finally tested against a panel of disease-related protein kinases.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"4 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435569","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}
ExTTF derivatives (1–4) bearing aryl groups attached through sulfur bridges have been synthesized. The peripheral aryl groups have a certain influence on both the electronic and crystallographic properties of the exTTFs. Compounds 1–4 show two bands typical of exTTF derivatives near 360 and 430 nm. Compound 1 and 4 exhibit the characteristic electrochemical exTTF behavior, with one reversible two‐electron process ranging depending on their substitution the electron‐withdrawing ability. But 2 and 3 exhibit a similar single two‐electron oxidation wave but electrochemically irreversible redox with peak‐to‐peak potential separation. And 3 has a low redox potential, which is significantly inconsistent with the electron absorption of pyridine substituents. The crystal structures of 1–4 exhibit the characteristic butterfly shape. Moreover, the peripheral aryl groups exhibit multiple alignment modes with respect to the central exTTF core, caused by their rotation about the two C−S bonds of the sulfur bridges. Under the interaction of multiple molecules, exTTF shows different molecular packing structures. Compounds 1–4 have charge transfer with C60 due to their good electron‐donating ability, butterfly configuration, and free rotation of peripheral aryl groups. These results indicate that 1–4 organic electronic materials have potential applications in the field of supramolecular assembly.
{"title":"Synthesis, Structures, and Physical Properties of ExTTF Substituted with Aryl Groups through Sulfur Bridges and the Electron Transfers with C60","authors":"Longfei Ma , Lingxi Wu , Xiaofeng Lu","doi":"10.1002/ejoc.202401193","DOIUrl":"10.1002/ejoc.202401193","url":null,"abstract":"<div><div>ExTTF derivatives (<strong>1</strong>–<strong>4</strong>) bearing aryl groups attached through sulfur bridges have been synthesized. The peripheral aryl groups have a certain influence on both the electronic and crystallographic properties of the exTTFs. Compounds <strong>1</strong>–<strong>4</strong> show two bands typical of exTTF derivatives near 360 and 430 nm. Compound <strong>1</strong> and <strong>4</strong> exhibit the characteristic electrochemical exTTF behavior, with one reversible two‐electron process ranging depending on their substitution the electron‐withdrawing ability. But <strong>2</strong> and <strong>3</strong> exhibit a similar single two‐electron oxidation wave but electrochemically irreversible redox with peak‐to‐peak potential separation. And <strong>3</strong> has a low redox potential, which is significantly inconsistent with the electron absorption of pyridine substituents. The crystal structures of <strong>1</strong>–<strong>4</strong> exhibit the characteristic butterfly shape. Moreover, the peripheral aryl groups exhibit multiple alignment modes with respect to the central exTTF core, caused by their rotation about the two C−S bonds of the sulfur bridges. Under the interaction of multiple molecules, exTTF shows different molecular packing structures. Compounds <strong>1</strong>–<strong>4</strong> have charge transfer with C<sub>60</sub> due to their good electron‐donating ability, butterfly configuration, and free rotation of peripheral aryl groups. These results indicate that <strong>1</strong>–<strong>4</strong> organic electronic materials have potential applications in the field of supramolecular assembly.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401193"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142696860","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}
Joaquín Marchán‐García , Prof. Mariana Álvarez , Prof. Gabriel Radivoy , Prof. Yanina Moglie
A green and sustainable approach to the direct synthesis of thioesters has been developed using Fe3O4 as a low‐cost, easily prepared, reusable and environmentally safe catalyst. The cross dehydrogenative coupling (CDC) of various thiols and aldehydes in water, or even in the absence of solvent, using tert‐butylhydroperoxide as oxidant, under ligand and base‐free mild conditions, afforded the corresponding thioesters in good to excellent yields. This simple protocol features broad substrate scope, good compatibility with different functional groups, as well as high atom‐efficiency. The scalability, ease of (magnetic) recovery and reuse of the magnetite catalyst are additional eco‐friendly attributes of this methodology. Moreover, the broad synthetic applications of thioesters further highlight the potential utility of the present protocol.
{"title":"Magnetite: a Green, Sustainable and Recyclable Catalyst for Direct Synthesis of Thioesters by C−H Activation","authors":"Joaquín Marchán‐García , Prof. Mariana Álvarez , Prof. Gabriel Radivoy , Prof. Yanina Moglie","doi":"10.1002/ejoc.202400827","DOIUrl":"10.1002/ejoc.202400827","url":null,"abstract":"<div><div>A green and sustainable approach to the direct synthesis of thioesters has been developed using Fe<sub>3</sub>O<sub>4</sub> as a low‐cost, easily prepared, reusable and environmentally safe catalyst. The cross dehydrogenative coupling (CDC) of various thiols and aldehydes in water, or even in the absence of solvent, using <em>tert</em>‐butylhydroperoxide as oxidant, under ligand and base‐free mild conditions, afforded the corresponding thioesters in good to excellent yields. This simple protocol features broad substrate scope, good compatibility with different functional groups, as well as high atom‐efficiency. The scalability, ease of (magnetic) recovery and reuse of the magnetite catalyst are additional eco‐friendly attributes of this methodology. Moreover, the broad synthetic applications of thioesters further highlight the potential utility of the present protocol.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202400827"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832394","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}
High‐throughput experimentation was employed to discover p‐Anisil as a highly effective and versatile catalysts for the E‐to‐Z photoisomerization of cinnamic acid derivatives and other activated alkenes. This new catalytic system tolerated a number of functional groups found in medicinal chemistry. The discovery enabled the preparation of previously unknown complex Z‐alkenes in two steps directly from drugs or peptides.
采用高通量实验发现，对苯胺是肉桂酸衍生物和其他活化烯烃E - to - Z光异构化的高效和通用催化剂。这种新的催化体系可耐受药物化学中发现的许多官能团。这一发现使得直接从药物或多肽两步制备以前未知的Z -烯烃络合物成为可能。
{"title":"p‐Anisil as a Versatile Catalyst for the E‐to‐Z Photoisomerization of Activated Alkenes ‐ Application in Late‐Stage Modification of Small Molecule Drugs, Di‐ and Tripeptides","authors":"Thanh V. Q. Nguyen , Peter R. Hansen","doi":"10.1002/ejoc.202401338","DOIUrl":"10.1002/ejoc.202401338","url":null,"abstract":"<div><div>High‐throughput experimentation was employed to discover <em>p</em>‐Anisil as a highly effective and versatile catalysts for the <em>E‐to‐Z</em> photoisomerization of cinnamic acid derivatives and other activated alkenes. This new catalytic system tolerated a number of functional groups found in medicinal chemistry. The discovery enabled the preparation of previously unknown complex <em>Z</em>‐alkenes in two steps directly from drugs or peptides.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401338"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815792","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}
Julian Friedrich, Marc Schmidtmann, Jens Christoffers
Bicyclic diketones and lactones are obtained in up to 60% yield in the aerobic, manganese‐catalyzed intramolecular radical cyclization of β‐oxoesters with a six‐membered ring and phenyl or diphenyl allyl substituents in the γ‐position. Intermediate products of this transformation are peroxides, which are processed either reductively with zinc–acetic acid or by Kornblum‐DeLaMare fragmentation (with acetyl chloride–pyridine). The respective congeners with five‐ or seven‐membered rings either undergo only α‐hydroxylation reactions or mixtures of various cyclization products are obtained in low yields. In this study, also cerium‐catalysis was investigated, however, the yields are lower compared to manganese catalysis. The relative configurations of all racemic products were established by X‐ray single crystal structure analyses.
{"title":"Investigations into Intramolecular Cerium‐ and Manganese‐Catalyzed Aerobic Coupling of β‐Oxoesters with Styryl Moieties","authors":"Julian Friedrich, Marc Schmidtmann, Jens Christoffers","doi":"10.1002/ejoc.202500158","DOIUrl":"https://doi.org/10.1002/ejoc.202500158","url":null,"abstract":"Bicyclic diketones and lactones are obtained in up to 60% yield in the aerobic, manganese‐catalyzed intramolecular radical cyclization of β‐oxoesters with a six‐membered ring and phenyl or diphenyl allyl substituents in the γ‐position. Intermediate products of this transformation are peroxides, which are processed either reductively with zinc–acetic acid or by Kornblum‐DeLaMare fragmentation (with acetyl chloride–pyridine). The respective congeners with five‐ or seven‐membered rings either undergo only α‐hydroxylation reactions or mixtures of various cyclization products are obtained in low yields. In this study, also cerium‐catalysis was investigated, however, the yields are lower compared to manganese catalysis. The relative configurations of all racemic products were established by X‐ray single crystal structure analyses.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"23 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427166","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}
Chiliveru Priyanka , Dr. Raju Adepu , Dr. Nagender Punna
At present, the research of organofluorine chemistry is a leading and rapidly emerging area of life sciences. Organofluorine molecules have drawn much attention by displaying a wide variety of applications in agrochemicals, medicines, fire extinguishers, and blowing agents. In the present review, the great advances made in the last decade for the asymmetric construction of quaternary stereocenters bearing trifluoromethyl group from the corresponding prochiral‐trifluoromethylated substrates are discussed. A variety of catalytic frameworks have been designed in this field for asymmetric induction. The main prochiral‐trifluoromethyl substrates chosen for this review are β‐CF3‐β‐substituted nitro alkenes and α, β‐ unsaturated trifluoromethyl ketones. Moreover, this review describes the further utilization of obtained CF3‐quaternary centres to access the important organofluorine molecules.
{"title":"Modern Approaches for Asymmetric Construction of CF3‐All Carbon Quaternary Stereocenters from Prochiral Trifluoromethyl Alkenes","authors":"Chiliveru Priyanka , Dr. Raju Adepu , Dr. Nagender Punna","doi":"10.1002/ejoc.202401168","DOIUrl":"10.1002/ejoc.202401168","url":null,"abstract":"<div><div>At present, the research of organofluorine chemistry is a leading and rapidly emerging area of life sciences. Organofluorine molecules have drawn much attention by displaying a wide variety of applications in agrochemicals, medicines, fire extinguishers, and blowing agents. In the present review, the great advances made in the last decade for the asymmetric construction of quaternary stereocenters bearing trifluoromethyl group from the corresponding prochiral‐trifluoromethylated substrates are discussed. A variety of catalytic frameworks have been designed in this field for asymmetric induction. The main prochiral‐trifluoromethyl substrates chosen for this review are <em>β</em>‐CF<sub>3</sub>‐<em>β</em>‐substituted nitro alkenes and <em>α, β</em>‐ unsaturated trifluoromethyl ketones. Moreover, this review describes the further utilization of obtained CF<sub>3</sub>‐quaternary centres to access the important organofluorine molecules.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401168"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044801","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 non‐covalent interactions in molecules play important roles towards their applications in various aspects such as molecular recognition, catalysis, supramolecular chemistry, structural biology, pharmacology etc. Interestingly, among various non‐bonding interactions, chalcogen bonding (ChB) has been extensively studied in different facets of crystal engineering over the last several years. The present study demonstrates the presence of Se⋅⋅⋅N or Se⋅⋅⋅Se ChB in the benzimidazole‐fused cyclic selenazonium selenocyanates (6–8), cyclic selenazinium selenocyanates (9–10) and the acyclic benzimidazolium analogs having two different types of selenocyanate units (11–12). The final organoselenium compounds were synthesized from benzimidazole in several steps in reasonably good yields. The single‐crystal X‐ray structures of the compounds revealed that both the N atom and Se atom of the negatively charged SeCN unit act as ChB acceptors in building the Se⋅⋅⋅N or Se⋅⋅⋅Se ChB interactions along with the additional hydrogen bonding (HB) interactions. Moreover, the structural optimization and natural bond orbital (NBO) analyses were carried out using density functional theory (DFT) to calculate the natural charges on different Se centers and the strength of second‐order perturbation energy (E2) for the ChB interactions. Finally, surface electrostatic potential (SEP) of the compounds was developed to visualize the formation of σ‐holes.
分子中的非共价相互作用在分子识别、催化、超分子化学、结构生物学、药理学等各方面的应用中发挥着重要作用。有趣的是，在各种非键相互作用中，钙原键（ChB）在过去几年中已在晶体工程的不同方面得到广泛研究。本研究表明，在苯并咪唑融合环硒唑硒氰酸酯（6-8）、环硒嗪硒氰酸酯（9-10）和具有两种不同类型硒氰酸酯单元的无环苯并咪唑类似物（11-12）中存在 Se-N 或 Se-Se ChB。最终的有机硒化合物是由苯并咪唑经过几个步骤合成的，收率相当高。这些化合物的单晶 X 射线结构显示，带负电荷的 SeCN 单元中的 N 原子和 Se 原子在建立 Se-N 或 Se-Se ChB 相互作用以及额外的氢键 (HB) 相互作用时都是 ChB 受体。此外，还利用密度泛函理论（DFT）进行了结构优化和天然键轨道（NBO）分析，以计算不同 Se 中心的天然电荷和 ChB 相互作用的二阶扰动能（E2）强度。最后，还开发了化合物的静电位面 (SEP)，以观察σ孔的形成。
{"title":"Structurally Innovative Benzimidazole‐fused Ionic Organoselenium Compounds: Prevalence of Se⋅⋅⋅N/Se Chalcogen Bonds with the Selenocyanate Receptor","authors":"Kaustav Banerjee , Abu Sufian , Krishna P. Bhabak","doi":"10.1002/ejoc.202401245","DOIUrl":"10.1002/ejoc.202401245","url":null,"abstract":"<div><div>The non‐covalent interactions in molecules play important roles towards their applications in various aspects such as molecular recognition, catalysis, supramolecular chemistry, structural biology, pharmacology etc. Interestingly, among various non‐bonding interactions, chalcogen bonding (ChB) has been extensively studied in different facets of crystal engineering over the last several years. The present study demonstrates the presence of Se⋅⋅⋅N or Se⋅⋅⋅Se ChB in the benzimidazole‐fused cyclic selenazonium selenocyanates (<strong>6–8</strong>), cyclic selenazinium selenocyanates (<strong>9–10</strong>) and the acyclic benzimidazolium analogs having two different types of selenocyanate units (<strong>11–12</strong>). The final organoselenium compounds were synthesized from benzimidazole in several steps in reasonably good yields. The single‐crystal X‐ray structures of the compounds revealed that both the N atom and Se atom of the negatively charged SeCN unit act as ChB acceptors in building the Se⋅⋅⋅N or Se⋅⋅⋅Se ChB interactions along with the additional hydrogen bonding (HB) interactions. Moreover, the structural optimization and natural bond orbital (NBO) analyses were carried out using density functional theory (DFT) to calculate the natural charges on different Se centers and the strength of second‐order perturbation energy (E<sup>2</sup>) for the ChB interactions. Finally, surface electrostatic potential (SEP) of the compounds was developed to visualize the formation of σ‐holes.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401245"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142596796","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}
This paper introduces an innovative strategy for the synthesis of multisubstituted allenes via nickel‐catalyzed reductive cross‐coupling reactions. The approach utilizes propargyl acetates and chlorosilanes to produce a variety of silyl‐substituted allenes. The reaction conditions are notably mild, and the process is characterized by high chemo‐ and regioselectivity, as well as an impressive substrate scope. Furthermore, the method can be readily extended to the use of chlorogermane and chlorostannane, facilitating the synthesis of germanium or stannium‐substituted allenes. This research not only offers a valuable strategy for the preparation of multisubstituted allenes but also significantly broadens the synthetic repertoire for the construction of highly functionalized molecules.
{"title":"Ni‐Catalyzed Synthesis of Multisubstituted Allenes via Reductive Cross‐Coupling of Propargylic Acetates with Chlorohydrosilanes","authors":"Xiaohui Yan , Hong Deng","doi":"10.1002/ejoc.202401234","DOIUrl":"10.1002/ejoc.202401234","url":null,"abstract":"<div><div>This paper introduces an innovative strategy for the synthesis of multisubstituted allenes via nickel‐catalyzed reductive cross‐coupling reactions. The approach utilizes propargyl acetates and chlorosilanes to produce a variety of silyl‐substituted allenes. The reaction conditions are notably mild, and the process is characterized by high chemo‐ and regioselectivity, as well as an impressive substrate scope. Furthermore, the method can be readily extended to the use of chlorogermane and chlorostannane, facilitating the synthesis of germanium or stannium‐substituted allenes. This research not only offers a valuable strategy for the preparation of multisubstituted allenes but also significantly broadens the synthetic repertoire for the construction of highly functionalized molecules.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401234"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809412","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}
Martin Huber , Matthias Schöbinger , Jordi Cirera , Berthold Stöger , Peter Weinberger
Four novel fluorescence active ligands (1–4) consisting of a 1H‐tetrazol‐1‐yl moiety as coordinating unit and a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) derivative as fluorophore, bridged via alkyl (‐(CH2)n‐, n=1–3) or benzyl (‐CH2‐C6H4‐) spacers were designed. Successful synthesis is demonstrated by multinuclear NMR spectroscopy, as well as powder and single crystal XRD analysis. The methylene bridged ligand 2 (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)methyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) crystallizes in different polymorphs and solvatomorphs, in contrast to the other three ligands, which show no polymorphism under identical conditions. Photophysical studies revealed high fluorescence quantum yields (69 – 95 %) in solution for the ‐(CH2)2‐ bridged ligand 3 (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)ethyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) and the ‐(CH2)3‐ bridged ligand 4 (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)propyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene). Non‐radiative decay due to rotational motion of the 1H‐tetrazol‐1‐yl‐ and/or ‐CH2‐C6H4‐ moiety for 2 and 1 (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[4‐((1H‐tetrazol‐1‐yl)methyl)phenyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) respectively leads to reduced quantum yields of ≥35 %. Complete fluorescence quenching upon aggregation is prevented by installation of the sterically demanding 1H‐tetrazol‐1‐yl moiety and a spacer in meso‐position of the BODIPY core to elongate the intermolecular distances between two adjacent BODIPY cores. Detailed photophysical and crystallographic investigations are supported by theoretical calculations.
{"title":"Design, Synthesis and Characterization of BODIPY based 1H‐Tetrazole Ligands","authors":"Martin Huber , Matthias Schöbinger , Jordi Cirera , Berthold Stöger , Peter Weinberger","doi":"10.1002/ejoc.202401239","DOIUrl":"10.1002/ejoc.202401239","url":null,"abstract":"<div><div>Four novel fluorescence active ligands (<strong>1</strong>–<strong>4</strong>) consisting of a 1H‐tetrazol‐1‐yl moiety as coordinating unit and a 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐<em>s</em>‐indacene (BODIPY) derivative as fluorophore, bridged <em>via</em> alkyl (‐(CH<sub>2</sub>)<sub>n</sub>‐, n=1–3) or benzyl (‐CH<sub>2</sub>‐C<sub>6</sub>H<sub>4</sub>‐) spacers were designed. Successful synthesis is demonstrated by multinuclear NMR spectroscopy, as well as powder and single crystal XRD analysis. The methylene bridged ligand <strong>2</strong> (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)methyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) crystallizes in different polymorphs and solvatomorphs, in contrast to the other three ligands, which show no polymorphism under identical conditions. Photophysical studies revealed high fluorescence quantum yields (69 – 95 %) in solution for the ‐(CH<sub>2</sub>)<sub>2</sub>‐ bridged ligand <strong>3</strong> (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)ethyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) and the ‐(CH<sub>2</sub>)<sub>3</sub>‐ bridged ligand <strong>4</strong> (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[(1H‐tetrazol‐1‐yl)propyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene). Non‐radiative decay due to rotational motion of the 1H‐tetrazol‐1‐yl‐ and/or ‐CH<sub>2</sub>‐C<sub>6</sub>H<sub>4</sub>‐ moiety for <strong>2</strong> and <strong>1</strong> (4,4‐difluoro‐1,3,5,7‐tetramethyl‐8‐[4‐((1H‐tetrazol‐1‐yl)methyl)phenyl]‐4‐bora‐3a,4a‐diaza‐s‐indacene) respectively leads to reduced quantum yields of ≥35 %. Complete fluorescence quenching upon aggregation is prevented by installation of the sterically demanding 1H‐tetrazol‐1‐yl moiety and a spacer in <em>meso</em>‐position of the BODIPY core to elongate the intermolecular distances between two adjacent BODIPY cores. Detailed photophysical and crystallographic investigations are supported by theoretical calculations.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 7","pages":"Article e202401239"},"PeriodicalIF":2.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ejoc.202401239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142600045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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