{"title":"Applications of Conia-ene reaction in total synthesis of natural products","authors":"Zhongting Ruan , Huaxuan Zhang , Fuhai Liu, Xingang Xie","doi":"10.1016/j.tet.2025.134901","DOIUrl":"10.1016/j.tet.2025.134901","url":null,"abstract":"<div><div>The Conia-ene reaction is an intramolecular alkenylation (or alkylation) reaction occurring at the carbonyl α position of unsaturated ketones and serves as a highly efficient transformation for the construction of cyclic ketones, especially those within five- or six-membered rings frequently encountered within natural products. Compared with the traditional thermal-promoted transformation, Lewis acid catalyzed Conia-ene features mild conditions and widely tolerable functional groups thereby has been widely applied in the synthesis of natural products. In this review, we briefly introduce the development of the Conia-ene reaction, recent advancements in protocols, and a comprehensive review of its application in the total synthesis of natural products.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134901"},"PeriodicalIF":2.2,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912045","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}
TetrahedronPub Date : 2025-08-27DOI: 10.1016/j.tet.2025.134897
Yongzhu Hu, Haoyu Wang, Zhenjiang Li, Yujia Wang, Min Zhang, Xin Yuan, Xin Zou, Chunyu Li, Tianyu Zhu, Kai Guo
{"title":"Resorcinarene bearing carbanion ion pair as organocatalyst for carbon dioxide fixation","authors":"Yongzhu Hu, Haoyu Wang, Zhenjiang Li, Yujia Wang, Min Zhang, Xin Yuan, Xin Zou, Chunyu Li, Tianyu Zhu, Kai Guo","doi":"10.1016/j.tet.2025.134897","DOIUrl":"10.1016/j.tet.2025.134897","url":null,"abstract":"<div><div>The development of efficient and environmentally friendly catalysts for carbon dioxide (CO<sub>2</sub>) cycloaddition remains a significant challenge due to the corrosion, pollution, and purity issues caused by conventional halide-containing systems. Herein, we present a halide-free tetra-1,3-diketone resorcinarene ion pair organocatalyst that facilitates CO<sub>2</sub> fixation under mild conditions (120 °C, 0.1 MPa) through a dual activation mechanism—CO<sub>2</sub> activation by the resorcinarene carbanion and epoxide activation via H-bonding. This catalytic system has been shown to achieve high conversion (83–99 %) for terminal epoxides, retain notable activity for internal epoxides, and demonstrate exceptional thermal stability (>230 °C) and recyclability (five cycles without significant loss of activity). This system offers a sustainable alternative to traditional halide catalysts, combining environmental advantages with practical industrial feasibility.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134897"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916883","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}
TetrahedronPub Date : 2025-08-27DOI: 10.1016/j.tet.2025.134902
Chun-Bo Ge , Si-Fan Liu , Zhi-Yan Zhang , Rui-Hong Li , Min Li , Zi-Ming Xia , Bin Li , Ying Tian , Guang-Jie Zhang , Shu-Chen Liu
{"title":"Total synthesis of orychophragine D via intramolecular Mitsunobu reaction and its radioprotective activity","authors":"Chun-Bo Ge , Si-Fan Liu , Zhi-Yan Zhang , Rui-Hong Li , Min Li , Zi-Ming Xia , Bin Li , Ying Tian , Guang-Jie Zhang , Shu-Chen Liu","doi":"10.1016/j.tet.2025.134902","DOIUrl":"10.1016/j.tet.2025.134902","url":null,"abstract":"<div><div>Orychophragine D (<strong>14</strong>) was an alkaloid, with a novel piperazine [1,2-a] [1,3,5] triazine molecular skeleton, obtained from the seeds of <em>Orychophragmus violaceus</em>. Previous studies had revealed the excellent radiation protection activity of <strong>14</strong>. In this study, the total synthesis of <strong>14</strong> was achieved for the first time. An intramolecular Mitsunobu reaction was applied in this study, where alcohol and nucleophile required for the reaction were cleverly integrated into one molecule. Moreover, the radioprotective activity of the synthesized <strong>14</strong> was verified, which increased the survival rate of HUVEC irradiated with a radiation dose of 15 Gy from 55.9 % to 75.1 %.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134902"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145118287","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}
TetrahedronPub Date : 2025-08-27DOI: 10.1016/j.tet.2025.134904
Natalia V. Kalganova , Alena Soboleva , Ivan Godovikov , Tatiana Bilova , Andrej Frolov , Ludger Wessjohann , Il'ya A. Cherepanov
{"title":"New type of 4,5-annelated bicyclic sydnone imines. Assessment of sydnone imines effectiveness as plant stress protectants","authors":"Natalia V. Kalganova , Alena Soboleva , Ivan Godovikov , Tatiana Bilova , Andrej Frolov , Ludger Wessjohann , Il'ya A. Cherepanov","doi":"10.1016/j.tet.2025.134904","DOIUrl":"10.1016/j.tet.2025.134904","url":null,"abstract":"<div><div>We report the multistep synthesis of a new array of 4,5-annelated bicyclic sydnone imine – (6-cyano-1-substituted-[1,2,3]oxadiazolo[5,4-<em>b</em>]pyridin-1-ium-5-yl)amide hydrochlorides. These bicyclic compounds are featured with the mesomeric charge spread out over the two fused aromatic fragments. Thus, these molecules can be considered as a new type of sydnone imine. The molecular structures of the bicyclic compounds were investigated in detail by X-ray and <sup>1</sup>H, <sup>13</sup>C, and <sup>15</sup>N NMR studies. In addition, the characterization of these compounds and their synthetic intermediaries was undertaken to ascertain their effectiveness as potential plant stress protectants or herbicides.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134904"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144997378","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}
{"title":"Viewing the Ritter reaction through single electron transfer lenses","authors":"Apurba Samanta, Saradindu Debnath, Palash Roy, Soumitra Maity","doi":"10.1016/j.tet.2025.134907","DOIUrl":"10.1016/j.tet.2025.134907","url":null,"abstract":"<div><div>Ritter reaction presents itself as the modern workhorse of amination reactions. What started as the amidation of tertiary carbon centres has spread to alkenes, carboxylic acids, as well as alkanes. The last decade has seen a tremendous increase in the utilization of Single Electron Transfer (SET) techniques in organic synthesis. Ritter amination has evolved along these lines as well, providing an unparalleled platform for incorporating amines into substrates of various types. In addition to photoredox and electrocatalytic niches, such SET-mediated reactions have been elegantly achieved using conventional oxidants, organocatalysts and transition metal-based complexes. In this review we present an in-depth discussion about the various reports on SET-based Ritter aminations, placing emphasis on the transition metal-mediated, organocatalytic, and conventional oxidant-based procedures in addition to the photoredox ones. The review is divided into two categories namely <em>Ritter amination of alkenes</em> and <em>Ritter amination of sp</em><sup><em>3</em></sup><em>-C centres</em> which are further sub-categorized appropriately with respect to the types of reactions.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134907"},"PeriodicalIF":2.2,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926455","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}
TetrahedronPub Date : 2025-08-26DOI: 10.1016/j.tet.2025.134905
Alexei N. Izmest'ev , Nikita A. Romanov , Andrey A. Streltsov , Natalya G. Kolotyrkina , Angelina N. Kravchenko , Galina A. Gazieva
{"title":"Application of 1,3-disubstituted thioureas as a key synthons for the synthesis of novel 5,7-disubstituted perhydroimidazo[4,5-e][1,2,4]triazinethiones","authors":"Alexei N. Izmest'ev , Nikita A. Romanov , Andrey A. Streltsov , Natalya G. Kolotyrkina , Angelina N. Kravchenko , Galina A. Gazieva","doi":"10.1016/j.tet.2025.134905","DOIUrl":"10.1016/j.tet.2025.134905","url":null,"abstract":"<div><div>A series of 1-alkyl-3-arylureas and thioureas, a key synthons for the synthesis of various heterocycles, have been synthesized. The corresponding 4,5-dihydroxyimidzolidin-2-ones and thiones were prepared from (thio)ureas with glyoxal, and the selectivity of their reaction with thiosemicarbazide was studied. Regioisomeric 7-alkyl-5-aryl- and 5-alkyl-7-aryl-3-thioxoperhydroimidazo[4,5-<em>e</em>][1,2,4]triazin-6-ones(thiones) were prepared and separated by fractional crystallization. Intermediate 3-alkyl-2-(1-(4-chlorophenyl)-5-ethoxy-2-oxoimidazolidin-4-yl)hydrazinecarbothioamides were also isolated. The structures of the regioisomers and intermediates were unambiguously determined by two-dimensional NMR NOESY spectral data and X-ray diffraction studies.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134905"},"PeriodicalIF":2.2,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144989089","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}
TetrahedronPub Date : 2025-08-25DOI: 10.1016/j.tet.2025.134903
Sipak Joyasawal , Marlyn S. Rada , Hadi Arman , Arnold R. Romero Bohórquez , Michael P. Doyle
{"title":"Amide hemiaminals from retro-Claisen ring opening of chiral 2-siloxy-1-cyclobutene-1-carboxamides","authors":"Sipak Joyasawal , Marlyn S. Rada , Hadi Arman , Arnold R. Romero Bohórquez , Michael P. Doyle","doi":"10.1016/j.tet.2025.134903","DOIUrl":"10.1016/j.tet.2025.134903","url":null,"abstract":"<div><div>Nucleophilic retro-Claisen ring opening of chiral <em>cis</em>-3,4-disubstituted cyclobutene-1-carboxamides with amines forms cyclic hemiaminals in good yield with complete retention of configuration. The chiral cyclobutene-1-carboxamides are prepared by [3 + 1]-cycloaddition of donor-acceptor 2-silyloxy-1-cyclopropene-1-carboxamides by copper(I) catalysis with chiral SaBox ligands with high cis selectivity in modest yields and enantioselectivities. Retro-Claisen ring opening by benzylamine formed the cyclic hemiaminal as the dominant product, but ring opening by cyclohexylamine gave the open form as the dominant product. The cyclic hemiaminal and open form are not interconvertible under the reaction conditions.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134903"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144922517","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}
TetrahedronPub Date : 2025-08-25DOI: 10.1016/j.tet.2025.134900
Kenji Kimura, Shinnosuke Wakamori, Ryo Katsuta, Ken Ishigami
{"title":"Synthesis and structure revision of wasulfisides: glucosyl disulfides isolated from wasabi","authors":"Kenji Kimura, Shinnosuke Wakamori, Ryo Katsuta, Ken Ishigami","doi":"10.1016/j.tet.2025.134900","DOIUrl":"10.1016/j.tet.2025.134900","url":null,"abstract":"<div><div>The first syntheses of three natural glucosyl disulfides—wasulfisides A, B, and 3-<em>epi</em>-wasulfiside B—were successfully accomplished. These compounds were originally isolated from wasabi (<em>Eutrema japonicum</em>) and possess a rare natural β-glucosyl disulfide motif. The core structure was efficiently constructed <em>via</em> S–S bond formation between a β-glucosyl thiotosylate and various thiols. The overall yields reached 37%, starting from <span>d</span>-glucose. Accordingly, the structure of wasulfiside A, a unique oxadithiocine-containing compound, was successfully revised based on the syntheses of its regio- and stereoisomers.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134900"},"PeriodicalIF":2.2,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144920110","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}
TetrahedronPub Date : 2025-08-24DOI: 10.1016/j.tet.2025.134898
Keshan Zhang , Donglin Zhang , Bo Cheng , Wenchao Zhang , Rongjie Yang
{"title":"Synthesis and characterization of octa(aminophenyl) silsesquioxane through amination of octa(nitrophenyl) silsesquioxane using B2(OH)4 at room temperature","authors":"Keshan Zhang , Donglin Zhang , Bo Cheng , Wenchao Zhang , Rongjie Yang","doi":"10.1016/j.tet.2025.134898","DOIUrl":"10.1016/j.tet.2025.134898","url":null,"abstract":"<div><div>Octa(aminophenyl) silsesquioxane (OAPS), a promising polyhedral oligomeric silsesquioxane (POSS) derivative, exhibits exceptional structural and functional properties, making it highly suitable for advanced material applications. In this study, we developed an efficient and sustainable synthesis method for OAPS, utilizing tetrahydroxydiboron [B<sub>2</sub>(OH)<sub>4</sub>] as a reducing agent and 4,4′-bipyridine as a catalytic mediator. This strategy streamlines the synthetic procedure through a metal-free approach, operating under mild conditions while achieving high yields and demonstrating exceptional process stability. Initially, octa(nitrophenyl) silsesquioxane (ONPS) was synthesized as the precursor. Through a comprehensive investigation and evaluation of different reducing agents, catalysts, and their quantities, a novel reduction strategy was developed, enabling the complete and efficient conversion of nitro groups to amino groups. The obtained OAPS was characterized by Fourier transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR), while matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) confirmed its high purity and structural integrity through molecular weight analysis. A proposed mechanistic pathway for the reduction process, facilitated by the synergistic action of B<sub>2</sub>(OH)<sub>4</sub> and 4,4′-bipyridine, is also proposed. The synthesized OAPS demonstrated remarkable thermal stability, with an initial decomposition temperature of 430.2 °C under nitrogen and 399.3 °C under air, highlighting its excellent performance. This study introduces a scalable and efficient method for OAPS synthesis, with significant potential for industrial applications in advanced materials and nanotechnology.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"186 ","pages":"Article 134898"},"PeriodicalIF":2.2,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902964","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}
TetrahedronPub Date : 2025-08-22DOI: 10.1016/j.tet.2025.134894
Thomas G. Back
{"title":"Selenosulfonation and related processes: Methods, mechanisms and synthetic applications","authors":"Thomas G. Back","doi":"10.1016/j.tet.2025.134894","DOIUrl":"10.1016/j.tet.2025.134894","url":null,"abstract":"<div><div>Selenosulfonates (RSO<sub>2</sub>SeR’) are versatile reagents that undergo free-radical or electrophilic additions to alkenes, alkynes, allenes and other unsaturated compounds with complementary regioselectivity. Such “selenosulfonations”, thus introduce two orthogonal functionalities that lend themselves to further useful transformations, such as selenoxide eliminations to form unsaturated sulfones and addition-elimination processes with a variety of organometallic reagents and other nucleophiles. The sulfone moiety is capable of stabilizing α-anions for further modification with electrophiles, as well as promoting conjugate additions and facilitating various cycloadditions when adjacent to a double or triple bond. Selenosulfonations of dienes and other polyunsaturated compounds can be employed in radical cyclizations. Furthermore, selenosulfonates serve as selenylating agents capable of introducing selenium substituents, including fluorinated alkylseleno groups, into a wide variety of substrates. The unique properties of selenosulfonates have led to a number of useful photoredox and polymer-supported processes, and have provided unsaturated sulfones for key steps in several total syntheses. While the emphasis of this review is on synthetic methodology, mechanistic explanations and applications to total synthesis are also covered.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":"187 ","pages":"Article 134894"},"PeriodicalIF":2.2,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145020123","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}