Pyrano[2,3,4‐ de ]quinoline‐encompassing scaffolds are high‐value, intricate synthetic targets that are of interest in medicinal chemistry. Herein, we illustrate the first example of a copper(I)‐catalyzed cascade Sonogashira coupling/annulation reaction of ethyl 4‐(benzoyloxy)‐5‐bromo‐6‐methylquinoline‐3‐carboxylate with internal alkynes. This methodology exhibits broad substrate scope with respect to the alkyne, with good functional‐group compatibility and promising yields.
{"title":"Expeditious Synthesis of Pyrano[2,3,4‐ de ]quinolines by a Copper(I)‐Catalyzed Cascade Sonogashira Coupling/Annulation Reaction","authors":"Anirban Mandal, Prasanjit Ghosh, Sajal Das","doi":"10.1002/ejoc.202500612","DOIUrl":"https://doi.org/10.1002/ejoc.202500612","url":null,"abstract":"Pyrano[2,3,4‐ <jats:italic>de</jats:italic> ]quinoline‐encompassing scaffolds are high‐value, intricate synthetic targets that are of interest in medicinal chemistry. Herein, we illustrate the first example of a copper(I)‐catalyzed cascade Sonogashira coupling/annulation reaction of ethyl 4‐(benzoyloxy)‐5‐bromo‐6‐methylquinoline‐3‐carboxylate with internal alkynes. This methodology exhibits broad substrate scope with respect to the alkyne, with good functional‐group compatibility and promising yields.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"20 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599425","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}
Diaryl ketones are versatile building blocks widely utilized in pharmaceuticals, materials science, and synthetic chemistry. Due to their structural importance and utility, many synthetic studies have been reported. Traditionally, diaryl ketones have been prepared via Friedel–Crafts acylation, even though this method suffers from limited functional group tolerance under acidic conditions. More recently, transition‐metal catalyzed strategies have emerged, typically involving the coupling between carbonyl electrophiles and organometallics. As an alternative, we report the reversed‐polarity synthesis of diaryl ketones using acylsilanes as carbonyl nucleophilic coupling partners in the presence of palladium catalyst. Inspired by our previous work on the synthesis of imines using imidoylsilanes, diaryliodonium salts were chosen as electrophilic partners. During optimization, the use of CsF was found to be essential, likely due to fluoride‐mediated activation of acylsilanes and facilitation of the transmetalation. Various functionalized diaryl ketones, including more complex derivatives bearing tetrahydrotetramethylnaphthalene (TMN) moieties, were successfully synthesized using this method, demonstrating the synthetic utility.
{"title":"Acylsilanes for Palladium‐Catalyzed Reversed‐Polarity Synthesis of Diaryl Ketones","authors":"Jaehoon Lee, Jaewon Lee, Inji Shin","doi":"10.1002/ejoc.202501008","DOIUrl":"https://doi.org/10.1002/ejoc.202501008","url":null,"abstract":"Diaryl ketones are versatile building blocks widely utilized in pharmaceuticals, materials science, and synthetic chemistry. Due to their structural importance and utility, many synthetic studies have been reported. Traditionally, diaryl ketones have been prepared via Friedel–Crafts acylation, even though this method suffers from limited functional group tolerance under acidic conditions. More recently, transition‐metal catalyzed strategies have emerged, typically involving the coupling between carbonyl electrophiles and organometallics. As an alternative, we report the reversed‐polarity synthesis of diaryl ketones using acylsilanes as carbonyl nucleophilic coupling partners in the presence of palladium catalyst. Inspired by our previous work on the synthesis of imines using imidoylsilanes, diaryliodonium salts were chosen as electrophilic partners. During optimization, the use of CsF was found to be essential, likely due to fluoride‐mediated activation of acylsilanes and facilitation of the transmetalation. Various functionalized diaryl ketones, including more complex derivatives bearing tetrahydrotetramethylnaphthalene (TMN) moieties, were successfully synthesized using this method, demonstrating the synthetic utility.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"29 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599427","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 Ru(II)‐ and Rh(III)‐catalyzed CH/CC bond activation and subsequent allylation of 2‐aryl‐3 H ‐indoles with vinylcyclopropanes (VCPs), 2‐vinyl‐ethylene oxide, and 2‐vinylaziridine are reported, enabling the expedient preparation of a wide spectrum for indole derivatives. This transformation proceeds using a cascade sequence involving CH bond activation, CC bond cleavage of VCPs, and 1,2‐migratory alkene insertion.
{"title":"Ruthenium‐ and Rhodium‐Catalyzed CH Bond Allylation of 2‐Aryl‐3 H ‐Indoles With Vinylcyclopropanes","authors":"Ze Li, Jianhui Wang","doi":"10.1002/ejoc.202500920","DOIUrl":"https://doi.org/10.1002/ejoc.202500920","url":null,"abstract":"The Ru(II)‐ and Rh(III)‐catalyzed CH/CC bond activation and subsequent allylation of 2‐aryl‐3 <jats:italic>H</jats:italic> ‐indoles with vinylcyclopropanes (VCPs), 2‐vinyl‐ethylene oxide, and 2‐vinylaziridine are reported, enabling the expedient preparation of a wide spectrum for indole derivatives. This transformation proceeds using a cascade sequence involving CH bond activation, CC bond cleavage of VCPs, and 1,2‐migratory alkene insertion.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"18 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599426","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}
Taylor Semeniuk, Austin Pounder, Dennis D. Toporkov, Stacey D. Wetmore, Jean‐Denys Hamel
Herein, we report the photocatalytic decarboxylative coupling of allylic difluorides and carbon‐centered radicals, which are formed from 2‐oxoacids. This mild and operationally simple protocol enables selective synthesis of monofluoroalkenes via defluorinative CC bond formation. Primary and aryl 2‐oxoacids undergo direct acyl radical addition to allylic difluorides, yielding acylated products exclusively. In contrast, secondary 2‐oxoacids afford mixtures of acylated and alkylated products, while tertiary 2‐oxoacids selectively deliver alkylated products via a decarboxylative/decarbonylation cascade. Thus, the product distribution can be tuned by the substitution pattern of the 2‐oxoacids. The rate of decarbonylation versus radical addition is based on the stability and reactivity of the radical intermediates formed. Computational studies confirm a substrate‐dependent divergence in reaction pathways, with primary 2‐oxoacids undergoing direct acyl radical addition, while secondary and tertiary substrates exhibit competing decarbonylation leading to alkylated products. This study therefore establishes a mechanistic rationale for competitive acylation/alkylation processes starting from 2‐oxoacids.
{"title":"Chemoselective Divergence via Substrate Control: Decarboxylative and Decarbonylative Coupling of 2‐Oxoacids with Allylic Difluorides","authors":"Taylor Semeniuk, Austin Pounder, Dennis D. Toporkov, Stacey D. Wetmore, Jean‐Denys Hamel","doi":"10.1002/ejoc.202501058","DOIUrl":"https://doi.org/10.1002/ejoc.202501058","url":null,"abstract":"Herein, we report the photocatalytic decarboxylative coupling of allylic difluorides and carbon‐centered radicals, which are formed from 2‐oxoacids. This mild and operationally simple protocol enables selective synthesis of monofluoroalkenes via defluorinative CC bond formation. Primary and aryl 2‐oxoacids undergo direct acyl radical addition to allylic difluorides, yielding acylated products exclusively. In contrast, secondary 2‐oxoacids afford mixtures of acylated and alkylated products, while tertiary 2‐oxoacids selectively deliver alkylated products via a decarboxylative/decarbonylation cascade. Thus, the product distribution can be tuned by the substitution pattern of the 2‐oxoacids. The rate of decarbonylation versus radical addition is based on the stability and reactivity of the radical intermediates formed. Computational studies confirm a substrate‐dependent divergence in reaction pathways, with primary 2‐oxoacids undergoing direct acyl radical addition, while secondary and tertiary substrates exhibit competing decarbonylation leading to alkylated products. This study therefore establishes a mechanistic rationale for competitive acylation/alkylation processes starting from 2‐oxoacids.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"167 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593787","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}
Shivaji V. Surve, Rajesh T. Bhawale, Biswajit Biswas, Umesh A. Kshirsagar
A visible‐light‐mediated regioselective C8 arylation of quinolinones has been developed by merging transition‐metal catalysis with photoredox catalysis. This approach offers broad substrate scope and mild reaction conditions, affording the desired products in up to 85% yield. Furthermore, to investigate the reaction mechanism, several control experiments were performed, including fluorescence quenching studies, quantum yield measurements, light‐on/off experiments, kinetic isotope effect (KIE) analysis, and H/D labeling experiments. This strategy exhibits excellent scalability and also enables subsequent C2 alkenylation.
{"title":"Palladium‐Catalyzed Photoinduced Regioselective C8 Arylation of 1‐(Pyridin‐2‐yl)quinolin‐4(1 H )‐Ones with Aryl Diazonium Salts","authors":"Shivaji V. Surve, Rajesh T. Bhawale, Biswajit Biswas, Umesh A. Kshirsagar","doi":"10.1002/ejoc.202500961","DOIUrl":"https://doi.org/10.1002/ejoc.202500961","url":null,"abstract":"A visible‐light‐mediated regioselective C8 arylation of quinolinones has been developed by merging transition‐metal catalysis with photoredox catalysis. This approach offers broad substrate scope and mild reaction conditions, affording the desired products in up to 85% yield. Furthermore, to investigate the reaction mechanism, several control experiments were performed, including fluorescence quenching studies, quantum yield measurements, light‐on/off experiments, kinetic isotope effect (KIE) analysis, and H/D labeling experiments. This strategy exhibits excellent scalability and also enables subsequent C2 alkenylation.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"47 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593786","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}
Julien Paut, Gabriel Goujon, Arnaud De Zordo‐Banliat, Guillaume Dagousset, Jorge Juan Cabrera‐Trujillo, Karinne Miqueu, Emmanuel Magnier, Bruce Pégot
Trifluoromethylselenide dichlorides are rare selenium(IV) derivatives that have received limited attention despite their potential in organoselenium chemistry. We report a straightforward and efficient synthesis of dichloro(aryl)(trifluoromethyl)‐λ 4 ‐selanes (ArSeCl 2 CF 3 ) via chlorination of aryl trifluoromethylselenides in acetonitrile as the solvent of choice. After evaluating various chlorinating agents, sulfuryl chloride (SO 2 Cl 2 ) revealed to be very efficient in a broad scope of substrates. Complementary density functional theory calculations provided mechanistic insight, indicating that chlorination proceeds via an asynchronous concerted mechanism with an accessible activation barrier and is exergonic, readily leading to the formation of Se(IV) fluorinated compounds. In contrast, the formation of the Se(VI) tetra‐chlorinated derivative via oxidative addition of Cl 2 to the Se(IV) derivative was found to be both kinetically and thermodynamically infeasible.
{"title":"Preparation of Se(IV) Aryltrifluoromethylselenide Dichlorides","authors":"Julien Paut, Gabriel Goujon, Arnaud De Zordo‐Banliat, Guillaume Dagousset, Jorge Juan Cabrera‐Trujillo, Karinne Miqueu, Emmanuel Magnier, Bruce Pégot","doi":"10.1002/ejoc.202500865","DOIUrl":"https://doi.org/10.1002/ejoc.202500865","url":null,"abstract":"Trifluoromethylselenide dichlorides are rare selenium(IV) derivatives that have received limited attention despite their potential in organoselenium chemistry. We report a straightforward and efficient synthesis of dichloro(aryl)(trifluoromethyl)‐λ <jats:sup>4</jats:sup> ‐selanes (ArSeCl <jats:sub>2</jats:sub> CF <jats:sub>3</jats:sub> ) via chlorination of aryl trifluoromethylselenides in acetonitrile as the solvent of choice. After evaluating various chlorinating agents, sulfuryl chloride (SO <jats:sub>2</jats:sub> Cl <jats:sub>2</jats:sub> ) revealed to be very efficient in a broad scope of substrates. Complementary density functional theory calculations provided mechanistic insight, indicating that chlorination proceeds via an asynchronous concerted mechanism with an accessible activation barrier and is exergonic, readily leading to the formation of Se(IV) fluorinated compounds. In contrast, the formation of the Se(VI) tetra‐chlorinated derivative via oxidative addition of Cl <jats:sub>2</jats:sub> to the Se(IV) derivative was found to be both kinetically and thermodynamically infeasible.","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"114 1","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145593788","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, an operationally simple photoinduced radical reduction of aryliodides and arylbromides using NHC‐borane as a reductant, without external radical initiator or photoredox catalyst, is reported. Mechanistic investigations indicate the key formation of an aryl radical, which undergoes facile reduction by NHC‐borane. The method demonstrates compatibility with a broad range of functional groups, providing a valuable tool for synthesis and isotopic labeling.
{"title":"Photoinduced Reduction and Deuteration of Aryl Halides with NHC‐Boranes","authors":"Gabin Lalande , Sandra Pinet , Frédéric Robert , Laurent Chabaud , Mathieu Pucheault","doi":"10.1002/ejoc.202500543","DOIUrl":"10.1002/ejoc.202500543","url":null,"abstract":"<div><div>Herein, an operationally simple photoinduced radical reduction of aryliodides and arylbromides using NHC‐borane as a reductant, without external radical initiator or photoredox catalyst, is reported. Mechanistic investigations indicate the key formation of an aryl radical, which undergoes facile reduction by NHC‐borane. The method demonstrates compatibility with a broad range of functional groups, providing a valuable tool for synthesis and isotopic labeling.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 43","pages":"Article e202500543"},"PeriodicalIF":2.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145116675","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}
Among the growing class of sp3‐rich scaffolds, spiro[3.3]heptane stands out for its rigid, 3D structure and favorable physicochemical properties. Its 3D saturated scaffold enables access to unique, nonplanar chemical space and has been explored as a saturated bioisostere of benzene in drug design. In this review, an overview of synthetic strategies developed to construct spiro[3.3]heptane derivatives is provided. These approaches are grouped according to key synthetic strategies, including formal [2+2] cyclization and bond disconnections at C1C2 or C4 (spiro‐carbon) positions. Representative examples are presented to illustrate each method's key transformations and strategic bond formations. This review is intended to support synthetic chemists interested in employing spiro[3.3]heptane as a building block and to provide a foundation for further exploration of this emerging motif.
{"title":"Spiro[3.3]heptane: A Versatile sp3‐Rich Scaffold and its Synthetic Routes","authors":"Myunggi Jung","doi":"10.1002/ejoc.202500738","DOIUrl":"10.1002/ejoc.202500738","url":null,"abstract":"<div><div>Among the growing class of sp<sup>3</sup>‐rich scaffolds, spiro[3.3]heptane stands out for its rigid, 3D structure and favorable physicochemical properties. Its 3D saturated scaffold enables access to unique, nonplanar chemical space and has been explored as a saturated bioisostere of benzene in drug design. In this review, an overview of synthetic strategies developed to construct spiro[3.3]heptane derivatives is provided. These approaches are grouped according to key synthetic strategies, including formal [2+2] cyclization and bond disconnections at C1C2 or C4 (spiro‐carbon) positions. Representative examples are presented to illustrate each method's key transformations and strategic bond formations. This review is intended to support synthetic chemists interested in employing spiro[3.3]heptane as a building block and to provide a foundation for further exploration of this emerging motif.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 43","pages":"Article e202500738"},"PeriodicalIF":2.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A heterogeneous iron‐anchored calcium aluminum hydrotalcite is prepared and characterized appropriately using powder X‐Ray diffraction, scanning electron microscope, energy dispersive X‐Ray, transmission electron microscope, ourier‐transform infrared, and thermogravimetric analysis. Further, X‐Ray photoelectron spectroscopy confirms the presence of Fe in +3 oxidation state. The prepared heterogeneous catalyst is applied to the selective synthesis of 2‐substituted benzimidazole and benzothiazole derivatives using alcohols and under solvent‐free reaction conditions. The developed protocol is applicable to a broad range of substrates, including difficult aliphatic substrates. The Fe/CaAl hydrotalcite catalyst can also be recycled and reused effectively for two catalytic cycles. Furthermore, control experiments reveal the role of the catalyst and the plausible mechanistic pathway of the reaction.
{"title":"Iron‐Doped Hydrotalcite: A Heterogeneous Catalyst for the Selective Synthesis of 2‐Substituted Benzimidazoles and Benzothiazoles Using Alcohols and Solvent‐Free Reaction Conditions","authors":"Pooja Devi Bora , Yabon Pame , Ramen Jamatia","doi":"10.1002/ejoc.202500759","DOIUrl":"10.1002/ejoc.202500759","url":null,"abstract":"<div><div>A heterogeneous iron‐anchored calcium aluminum hydrotalcite is prepared and characterized appropriately using powder X‐Ray diffraction, scanning electron microscope, energy dispersive X‐Ray, transmission electron microscope, ourier‐transform infrared, and thermogravimetric analysis. Further, X‐Ray photoelectron spectroscopy confirms the presence of Fe in +3 oxidation state. The prepared heterogeneous catalyst is applied to the selective synthesis of 2‐substituted benzimidazole and benzothiazole derivatives using alcohols and under solvent‐free reaction conditions. The developed protocol is applicable to a broad range of substrates, including difficult aliphatic substrates. The Fe/CaAl hydrotalcite catalyst can also be recycled and reused effectively for two catalytic cycles. Furthermore, control experiments reveal the role of the catalyst and the plausible mechanistic pathway of the reaction.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 43","pages":"Article e202500759"},"PeriodicalIF":2.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145215859","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}
Erik Kalla , Hugo Semrád , Lukáš Maier , Kamil Paruch , Hendrik Zipse , Markéta Munzarová
Diels–Alder reactions of 2‐methyl‐6‐substituted‐p‐benzoquinones are studied using quantum chemical calculations. The effect of 19 substituents, including halomethyl, alkyl, vinyl, ethynyl, nitrile, trifluoromethyl, methoxy, cyclohexenyl, phenyl, and trifluoromethoxyphenyl groups, on the reaction barriers is explored by the B3LYP‐D3, M06‐2X, and DLPNO‐CCSD(T) methods. Gibbs free activation energies are compared for the two regioisomeric products experimentally observed in the reaction mixture. For 75% of the substituents, the calculated barrier difference (ΔG‡b – ΔG‡a) lies within 2.0 kcal mol−1 of the value determined from the experimentally observed product ratio a/b. Activation barriers are further analyzed in terms of the underlying deformation and interaction energies. The difference in deformation energies of transition states corresponding to the two regioisomers ranges from −8.0 to +8.0 kcal mol−1 and is directly proportional to experimental ln(a/b) values. Differences in interaction energies between regioisomeric transition states are, in comparison, significantly smaller.
{"title":"Exploring the Regioselectivity of Diels–Alder Reactions of 2,6‐Disubstituted Benzoquinones through DFT Calculations","authors":"Erik Kalla , Hugo Semrád , Lukáš Maier , Kamil Paruch , Hendrik Zipse , Markéta Munzarová","doi":"10.1002/ejoc.202500661","DOIUrl":"10.1002/ejoc.202500661","url":null,"abstract":"<div><div>Diels–Alder reactions of 2‐methyl‐6‐substituted‐<em>p</em>‐benzoquinones are studied using quantum chemical calculations. The effect of 19 substituents, including halomethyl, alkyl, vinyl, ethynyl, nitrile, trifluoromethyl, methoxy, cyclohexenyl, phenyl, and trifluoromethoxyphenyl groups, on the reaction barriers is explored by the B3LYP‐D3, M06‐2X, and DLPNO‐CCSD(T) methods. Gibbs free activation energies are compared for the two regioisomeric products experimentally observed in the reaction mixture. For 75% of the substituents, the calculated barrier difference (Δ<em>G</em><sup>‡</sup><strong>b</strong> – Δ<em>G</em><sup>‡</sup><strong>a</strong>) lies within 2.0 kcal mol<sup>−1</sup> of the value determined from the experimentally observed product ratio <strong>a</strong>/<strong>b</strong>. Activation barriers are further analyzed in terms of the underlying deformation and interaction energies. The difference in deformation energies of transition states corresponding to the two regioisomers ranges from −8.0 to +8.0 kcal mol<sup>−1</sup> and is directly proportional to experimental ln(<strong>a</strong>/<strong>b</strong>) values. Differences in interaction energies between regioisomeric transition states are, in comparison, significantly smaller.</div></div>","PeriodicalId":167,"journal":{"name":"European Journal of Organic Chemistry","volume":"28 43","pages":"Article e202500661"},"PeriodicalIF":2.7,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145182759","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：