Organic Chemistry Frontiers最新文献

{"title":"Synthesis and Chiral Self-Sorting of Spirobifluorene-Containing Boronate Ester Cages","authors":"Natalie Schäfer, Lukas Glanz, Arne Lützen, Florian Beuerle","doi":"10.1039/d4qo02012j","DOIUrl":"https://doi.org/10.1039/d4qo02012j","url":null,"abstract":"2,2’-Functionalization induces axial chirality within the orthogonal aromatic scaffold of 9,9’-bispirofluorene. By implementing boronic acids at these positions, well-suited precursors for chiral boronate ester cages are generated. As a key intermediate, <em>(P)</em>-9,9’-bispirofluorene-2,2’-bistriflate <em>(P)</em>-5 was synthesized via a four-step sequence of twofold Friedel-Crafts acylation, Baeyer-Villiger oxidation, hydrolysis, and triflate formation. Chiral resolution was achieved via chiral HPLC for the dihydroxy intermediate. In a modular manner, Pd-catalyzed borylation or cross-coupling afforded either diboronic acid <em>(P)</em>-<strong>B*</strong> or elongated derivative <em>(P)</em>-<strong>B*<small>^Ph</small></strong> possessing additional phenylene spacers. For both enantiomerically pure linkers, reaction with hexahydroxy tribenzitriquinacene <strong>A</strong> in THF under water-removing conditions afforded isoreticular chiral organic cages <em>(P,P,P)</em>-<strong>A<small>₂</small>B*<small>₃</small></strong> and <em>(P,P,P)</em>-<strong>A<small>₂</small>B*<small>^Ph</small><small>₃</small></strong>. Both cages possess a chiral trigonal-bipyramidal geometry and were characterized by <small>¹</small>H, <small>¹³</small>C and DOSY NMR spectroscopy and MALDI-TOF mass spectrometry. Chiral self-sorting of the bispirofluorene precursors was investigated by reactions of <strong>A </strong>with racemic linkers <em>rac</em>-<strong>B*</strong> and <em>rac</em>-<strong>B*<small>^Ph</small></strong>. For shorter linker <em>rac</em>-<strong>B*</strong>, quantitative self-sorting into a racemic mixture of <em>(P,P,P)</em>-<strong><strong>A<small>₂</small>B*<small>₃</small></strong></strong> and <em>(M,M,M)</em>-<strong>A<small>₂</small>B*<small>₃</small></strong> occurred. For elongated derivative <em>rac</em>-<strong>B*<small>^Ph</small></strong> however, the increased flexibility introduced by the phenylene extension resulted in much lower selectivity and self-recognition. Instead a more complex product mixture was obtained and the racemic mixture of <strong>A<small>₂</small>B*<small>^ph</small><small>₃</small></strong> was isolated in much lower yield of around 20%. Semiempirical PM6 calculations for both homo- and heterochiral cages and macrocyclic intermediates allowed for an estimation of macrocyclic strain energies and provided in-depht insight into cage formation pathways and self-sorting properties.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"10 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mastering Palladium Catalyzed Cross-Coupling Reactions: The Critical Role of In Situ Pre-catalyst Reduction Design.","authors":"Tommaso Fantoni, Chiara Palladino, Riccardo Grigolato, Beatrice Muzzi, Lucia Ferrazzano, Alessandra Tolomelli, Walter Cabri","doi":"10.1039/d4qo02335h","DOIUrl":"https://doi.org/10.1039/d4qo02335h","url":null,"abstract":"Palladium catalyzed cross coupling reactions are among the most used methods for carbon-carbon bond formation in the agrochemical and pharmaceutical segments. The key step common to all methodologies based on Pd(0) catalysis is the generation in situ of the active catalyst. The paper describes how to control pre-catalysts reduction in order to generate the target complex species avoiding phosphine oxidation or, as in the case of the Heck-Cassar-Sonogashira and the Suzuki-Miyaura reactions, reactants consumption via dimerization. For PPh3, DPPF, DPPP, Xantphos, SPhos, RuPhos, XPhos and sSPhos we identified protocols able to maximize the reduction via alcohol preserving ligands and reagents. The correct combination of counterion, ligand, and base allowed to perfectly control the Pd(II) reduction to Pd(0) in the presence of primary alcohols.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"2 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantioselective Synthesis of Vicinal Diamines and β-Amino Amides by NiH-Catalyzed Hydroamidation of Alkenyl Amides","authors":"Xun Tian, Shengzu Duan, Yuan Ma, Ailin Pan, Yamiao Meng, guogang deng, Hongbin Zhang, Xiaodong Yang","doi":"10.1039/d4qo02275k","DOIUrl":"https://doi.org/10.1039/d4qo02275k","url":null,"abstract":"Enantioenriched diamines and β-amino amides are privileged scaffolds in organic and medicinal chemistry, which exhibit many applications in natural products and pharmaceutical molecules, as well as asymmetric catalysis. Catalytic asymmetric hydroamidation is considered one of the easiest ways to obtain such compounds in enantioenriched form. Here we report a NiH/BOX-catalyzed enantioselective hydroamidation of alkenyl amides and dioxazolones. The described transformation provides a series of enantioenriched vicinal diamines and β-amino amides, including structural modification of natural products and bioactive molecules and the preparation of chiral radical scavenger Nicaraven. A broad range of functional groups are well-tolerated under room temperature with high enantioselectivities (up to 99%) and good yields (up to 87%). Mechanistic studies including capture of metal-nitrenoid intermediate and competitive experiment provide significant evidence for this hydroamidation process.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"16 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142991923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atom-controlled divergent synthesis of spiro and fused rings via base-catalyzed chemoselective annulation","authors":"Gang Chen, Guangjie Nie, Linxuan Li, Jie Fu, Hui Yao, Nianyu Huang, Nengzhong Wang","doi":"10.1039/d4qo02400a","DOIUrl":"https://doi.org/10.1039/d4qo02400a","url":null,"abstract":"Annulation reactions are recognized for their efficiency in constructing complex cyclic compounds with multiple substitutions, aligning well with green chemistry principles. Herein, we report a transition metal-free, chemodiverse cycloaddition reaction employing allylamine as [C,N] synthons that react with azadienes in an environmentally benign manner. The protocol has been applied to benzofuran- and indanone-derived azadienes via [3+2] cycloadditions, and to benzothiophene-derived azadienes via [3+4] cycloadditions, yielding a series of spirobenzofurans, spirotetrandrines, and benzothiophene-diazepines with high diastereoselectivity. In addition to avoiding the use of toxic transition metals, the process demonstrates the potential for further functional group transformations of cycloaddition products, paving the way the sustainable generation of valuable intermediates.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"33 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HFIP-promoted formal [2π + 2σ] cycloaddition of para-quinone methides with bicyclo[1.1.0]butanes: approach to spiro-bicyclo[2.1.1]hexanes","authors":"Haijian Wu, Manman Sun, Jing Zhang, Zhiming Wang, Jianguo Yang, Gangguo Zhu","doi":"10.1039/d4qo02226b","DOIUrl":"https://doi.org/10.1039/d4qo02226b","url":null,"abstract":"A formal [2π + 2σ] cycloaddition of BCBs with p-QMs has been developed using a small amount of HFIP (2 M) as the solvent without an additional catalyst, in which HFIP also served as a H-bond donor and a cationic stabilizer. This protocol provides a rapid construction of spiro-BCHs in good to excellent yields with a broad substrate scope. Easy scale-up synthesis, potential application in modifications of bioactive products, mild reaction conditions and simple operation show practical advantages.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"58 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enantiopure Piperidines via Stereoselective Ireland-Claisen Rearrangement: Entry into Corynanthe Alkaloids","authors":"Niklāvs Ūdris, Rebeka Ločmele, J. Pelss, Anastasija Ture, Guna Sakaine, Artis Kinens, Gints Smits","doi":"10.1039/d4qo02235a","DOIUrl":"https://doi.org/10.1039/d4qo02235a","url":null,"abstract":"A fully stereo-divergent Ireland-Claisen rearrangement of achiral lactones has been developed enabling access to all four possible stereoisomers of 3,4-disubstituted piperidines and pyrrolidines. The utility of these building blocks has been showcased in the total synthesis of meroquinene ester and cardioprotective indole alkaloids sitsirikine and dihydrositsirikine.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"57 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142992607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spiroamentotaxols A–D: unprecedented 6/6/6/5/6/6/6/6 spiro-octacyclic bis-diterpene heterodimers from the endangered conifer Amentotaxus yunnanensis and their bioactivities","authors":"Peng-Jun Zhou, Ze-Yu Zhao, Sha Chen, Gong-Pu Luo, Jin-Xin Zhu, Xu-Wen Li, Yeun-Mun Choo, Mark T. Hamann, Juan Xiong, Jin-Feng Hu","doi":"10.1039/d4qo02210f","DOIUrl":"https://doi.org/10.1039/d4qo02210f","url":null,"abstract":"As a new chemical class of bis-diterpene heterodimers, spiroamentotaxols A–D (<strong>1–4</strong>) are characterized by a complex 6/6/6/5/6/6/6/6 spiro-octacyclic ring system, which is likely biogenetically derived from a Diels–Alder [4 + 2] cycloaddition between an <em>ent</em>-kaurene and a C<small>₂₀</small>-norabietane. The spiroamentotaxols possess a distinctive spiro[bicyclo[3.2.1]octane-7,2′-bicyclo[2.2.2]octene] motif. Through the application of molecular ion networking (MoIN), these intermolecular Diels–Alder isomers were isolated from the renewable twigs and needles of the endangered Chinese conifer <em>Amentotaxus yunnanensis</em>. Their chemical structures were elucidated using spectroscopic methods, electronic circular dichroism calculations, and X-ray diffraction analysis. From a structural diversity perspective, two semi-synthetic analogs, namely, 7′-deoxy-6′-en-spiroamentotaxol A (<strong>1a</strong>) and 7′-deoxy-spiroamentotaxol A (<strong>1b</strong>), were synthesized from the relatively major compound <strong>1</strong>. These spiro-polycyclic compounds were evaluated for their <em>in vitro</em> anti-inflammatory and anticancer activities. In particular, compound <strong>1</strong> attenuated inflammation in both RAW 264.7 macrophage and BV2 microglial cells at a non-toxic concentration of 20 μM, with the lipopolysaccharide (LPS)-induced nitric oxide production inhibition rates of 46.66% and 32.37%, respectively. <strong>1b</strong> exhibited efficacy against a panel of human cancer cell lines (A549, MCF7, HCT116, RKO, and HepG2), with IC<small>₅₀</small> values ranging from 6.27 to 14.10 μM. In the case of HCT116 cells, <strong>1b</strong> specifically influenced cell-cycle progression at the G2 phase and induced apoptosis. The findings highlight the importance of conserving plant species diversity as a means to sustain chemical diversity and serve as a potential source of new therapeutic agents for cancer treatment.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"74 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visible-Light Mediated Cobaloxime-Catalyzed Isomerization and Hydroalkenylation of Bicyclo[1.1.0]butanes","authors":"Ben Mao, Sheng-Hao Jiang, Zheng Xiong, Yin Wei, Min Shi","doi":"10.1039/d5qo00020c","DOIUrl":"https://doi.org/10.1039/d5qo00020c","url":null,"abstract":"Bicyclo[1.1.0]butanes have received extensive attention from chemists in recent years and diverse approaches to access transformations of such strained molecules have been explored. Since cobalt catalysis become a promising field in organic synthesis, the cobalt-catalyzed strain-release strategy of bicyclobutanes is still underdeveloped. Herein, we disclose a visible-light driven cobaloxime-catalyzed protocol for bicyclo[1.1.0]butanes transformations. A range of cyclobutene and alkenylated cyclobutane products have been obtained in moderate to excellent yields with excellent functional group tolerance. Synthetic applications of this protocol were conducted with several transformations. Moreover, a series of control experiments and spectroscopic experiments were performed to demonstrate the reaction mechanism.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"30 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142990905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Redox reaction between N-heterocyclic carbenes and sulfonates: insights into unproductive catalytic paths","authors":"Jia Song, Wei Wang, Guanjie Wang, Wen-Xin Lv","doi":"10.1039/d4qo02196g","DOIUrl":"https://doi.org/10.1039/d4qo02196g","url":null,"abstract":"Unproductive consumption of catalysts is a common hurdle in developing efficient catalytic reactions. In the realm of N-heterocyclic carbene (NHC) organic catalysis, attention has mainly been focused on the involvement of air (oxygen) and water in the deactivation (unproductive consumption) of the catalysts. Here, we disclose that the carbene catalyst can react with sulfonates <em>via</em> a redox process that converts NHCs into the corresponding urea molecules. This process involves rather complicated steps that ultimately transfer the oxygen atom from the sulfonate to the carbene. NHCs with different structures exhibit varying degrees of tendency in the oxidation process. Since many substrates and reagents involved in NHC catalysis possess oxidizing abilities, our study suggests that investigating potential redox processes of NHC catalysts is crucial for developing future generations of effective NHC catalysts and reactions. Our study also offers new mechanistic insights into the possible reactivities of NHCs and their adducts with other molecules.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"77 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Divergent application of 5-amino-isoxazoles for the construction of nitrogen heterocycles via the hydride transfer strategy","authors":"Mengzhe Pan, Feng-Wei Guo, Xinjie Sun, Jie Zhang, Wei Lu, Lubin Xu, Fangzhi Hu, Shuai-Shuai Li","doi":"10.1039/d4qo02059f","DOIUrl":"https://doi.org/10.1039/d4qo02059f","url":null,"abstract":"The hydride transfer-enabled divergent application of 5-amino-isoxazoles for the controllable construction of diverse tetrahydroquinolines and tetrahydroquinazolines was disclosed unprecedentedly by the process of ring-cleavage/Beckmann rearrangement, dearomative-spirocyclization, or <em>N</em>,<em>N</em>′-dialkylation of the amino group with the employment of different Lewis acids.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"27 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}