The Wurtz reaction is a classical C(sp3)–C(sp3) bond-forming reaction involving alkyl halides and alkali metals. However, this reaction generally requires molten or dispersed metals in large amounts of solvent, and has poor functional-group tolerance. Herein, we report a mechanochemical Wurtz reaction by the direct ball-milling of bulk Li, Na, and Ca with haloalkanes. The mechanochemical grinding of these bulk metals with a small amount of a liquid additive (THF) generates highly dispersed reactive metal species, enabling efficient C–C bond formation at room temperature even under air. Under optimized reaction conditions with Li and Na, various primary and secondary haloalkanes are converted into higher-order alkanes. Furthermore, the mechanochemical grinding of Ca is particularly effective for the Wurtz reaction of bromoalkanes bearing various functional groups such as fluoro, chloro, keto, and ester groups, achieving unprecedented C–C coupling and one-step furan synthesis. The developed reaction also allows gram-scale synthesis with a minimal amount of solvent, offering a practical and complementary method to the classical in-solution Wurtz reaction.
{"title":"Alkali/alkaline earth metal-mediated mechanochemical Wurtz reactions","authors":"Yoshifumi Toyama, Hideto Ito","doi":"10.1039/d6qo00142d","DOIUrl":"https://doi.org/10.1039/d6qo00142d","url":null,"abstract":"The Wurtz reaction is a classical C(sp<small><sup>3</sup></small>)–C(sp<small><sup>3</sup></small>) bond-forming reaction involving alkyl halides and alkali metals. However, this reaction generally requires molten or dispersed metals in large amounts of solvent, and has poor functional-group tolerance. Herein, we report a mechanochemical Wurtz reaction by the direct ball-milling of bulk Li, Na, and Ca with haloalkanes. The mechanochemical grinding of these bulk metals with a small amount of a liquid additive (THF) generates highly dispersed reactive metal species, enabling efficient C–C bond formation at room temperature even under air. Under optimized reaction conditions with Li and Na, various primary and secondary haloalkanes are converted into higher-order alkanes. Furthermore, the mechanochemical grinding of Ca is particularly effective for the Wurtz reaction of bromoalkanes bearing various functional groups such as fluoro, chloro, keto, and ester groups, achieving unprecedented C–C coupling and one-step furan synthesis. The developed reaction also allows gram-scale synthesis with a minimal amount of solvent, offering a practical and complementary method to the classical in-solution Wurtz reaction.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"193 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381096","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}
Yan Zhang, An Lin, Cuitong Zhou, Jing-Yuan Liu, Yahuan Wang, Xinwei Zhu, Lebin Su, Kuangbiao Liao
Arylaldehyde hydrazones are versatile building blocks for organic transformations, yet their ortho-C(sp²)-H functionalization remains underdeveloped. Herein, we report a general rhodium-catalyzed method for the direct ortho-C(sp²)-H amidation of arylaldehyde hydrazones with dioxazolones, enabled by high-throughput experimentation (HTE) and machine learning (ML). This operationally simple method affords diverse orthoamide-functionalized aryl derivatives (e.g., hydrazones, carboxylic acids, nitriles) in moderate to excellent yields with broad substrate scope (>60 examples), excellent functional group tolerance, and high chemoselectivity under mild conditions, facilitating versatile product derivatization. Moreover, a comprehensive exploration of the reaction space (1000 reactions) facilitated training of an XGBoost model using RDKit descriptors for yield prediction, achieving a mean absolute error (MAE) of 5.2% on an external validation set and demonstrating accurate predictive capability beyond the training set.
{"title":"High-throughput screening and machine learning prediction of Rh-catalyzed ortho-C(sp²)–H amidation of arylaldehyde hydrazones","authors":"Yan Zhang, An Lin, Cuitong Zhou, Jing-Yuan Liu, Yahuan Wang, Xinwei Zhu, Lebin Su, Kuangbiao Liao","doi":"10.1039/d6qo00026f","DOIUrl":"https://doi.org/10.1039/d6qo00026f","url":null,"abstract":"Arylaldehyde hydrazones are versatile building blocks for organic transformations, yet their ortho-C(sp²)-H functionalization remains underdeveloped. Herein, we report a general rhodium-catalyzed method for the direct ortho-C(sp²)-H amidation of arylaldehyde hydrazones with dioxazolones, enabled by high-throughput experimentation (HTE) and machine learning (ML). This operationally simple method affords diverse orthoamide-functionalized aryl derivatives (e.g., hydrazones, carboxylic acids, nitriles) in moderate to excellent yields with broad substrate scope (>60 examples), excellent functional group tolerance, and high chemoselectivity under mild conditions, facilitating versatile product derivatization. Moreover, a comprehensive exploration of the reaction space (1000 reactions) facilitated training of an XGBoost model using RDKit descriptors for yield prediction, achieving a mean absolute error (MAE) of 5.2% on an external validation set and demonstrating accurate predictive capability beyond the training set.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"15 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381066","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}
Seyed Mohammad-Bagher-Hosseini Ghazvini, Diego Cordova, Ingrid Dell, Elena Dallerba, Carol Hua, Paul Low, Massimiliano Massi, Marcus Korb
The acid-mediated activation of hexa-2,4-diyne-1,6-diols (1) is the standard protocol for the formation of valuable strained 1,2-dihalocyclobutenes/1,2-dihalobutafulvenes (3). However, the reaction is sluggish, associated with poor yields caused by formation of various unknown byproducts, and so far limited to only two examples. Herein, detailed mechanistic studies revealed the nature of the by-products with the kinetically preferred product class identified as 5-vinyl-3(2H)-furanones (4), of which only a few examples are reported. Electron-donating substrates favor sequential dehydroxylation, stabilizing discrete allenylic cations that undergo rapid halogen capture into dibromo bisallenes (2) and subsequent conrotatory electrocyclization into 1,2-dibromocyclobutenes. In contrast, electron-withdrawing substituents redirect the reaction toward selective hydration and 5-exo-dig cyclization into regio-defined 5-vinyl-3(2H)-furanones. DFT analysis, electronic-structure correlations, and single-crystal X-ray diffraction rationalize the divergent pathways and the influence of steric congestion on allene cyclization. Mechanistic studies using asymmetric diols (Ar1)2C(OH)–C≡C–C≡C–C(OH)(Ar2)2 (Ar1 ≠ Ar2) yielded single regio-isomeric 5-vinyl-furan-3(2H)-ones. The 3(2H)-furanones can undergo selective C4 functionalization and cross-coupling, providing fluorescent scaffolds with tunable emission across the visible spectrum increasing from 550 to 665 nm via 4-R = Br < C≡C-C6H4-4-OMe.
{"title":"Electronic Modification of Hexa-2,4-diyne-1,6-diols: Predictive Access to Strained Cyclobutenes and 3(2H)-Furanones","authors":"Seyed Mohammad-Bagher-Hosseini Ghazvini, Diego Cordova, Ingrid Dell, Elena Dallerba, Carol Hua, Paul Low, Massimiliano Massi, Marcus Korb","doi":"10.1039/d6qo00056h","DOIUrl":"https://doi.org/10.1039/d6qo00056h","url":null,"abstract":"The acid-mediated activation of hexa-2,4-diyne-1,6-diols (<strong>1</strong>) is the standard protocol for the formation of valuable strained 1,2-dihalocyclobutenes/1,2-dihalobutafulvenes (<strong>3</strong>). However, the reaction is sluggish, associated with poor yields caused by formation of various unknown byproducts, and so far limited to only two examples. Herein, detailed mechanistic studies revealed the nature of the by-products with the kinetically preferred product class identified as 5-vinyl-3(2<em>H</em>)-furanones (<strong>4</strong>), of which only a few examples are reported. Electron-donating substrates favor sequential dehydroxylation, stabilizing discrete allenylic cations that undergo rapid halogen capture into dibromo bisallenes (<strong>2</strong>) and subsequent conrotatory electrocyclization into 1,2-dibromocyclobutenes. In contrast, electron-withdrawing substituents redirect the reaction toward selective hydration and 5-exo-dig cyclization into regio-defined 5-vinyl-3(2<em>H</em>)-furanones. DFT analysis, electronic-structure correlations, and single-crystal X-ray diffraction rationalize the divergent pathways and the influence of steric congestion on allene cyclization. Mechanistic studies using asymmetric diols (Ar<small><sup>1</sup></small>)<small><sub>2</sub></small>C(OH)–C≡C–C≡C–C(OH)(Ar<small><sup>2</sup></small>)<small><sub>2</sub></small> (Ar<small><sup>1</sup></small> ≠ Ar<small><sup>2</sup></small>) yielded single regio-isomeric 5-vinyl-furan-3(2<em>H</em>)-ones. The 3(2<em>H</em>)-furanones can undergo selective C4 functionalization and cross-coupling, providing fluorescent scaffolds with tunable emission across the visible spectrum increasing from 550 to 665 nm via 4-R = Br < C≡C-C<small><sub>6</sub></small>H<small><sub>4</sub></small>-4-OMe.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"130 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358783","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}
The development of sustainable methods for controlled C-N bond formation remains a central challenge in modern synthesis. Here we report an operationally simple, catalyst-free and acid/base-free electrochemical platform that enables the direct single-electron activation of N-carbazates to generate a versatile diazene-centred radical under direct current (DC) or rapid alternating polarity current (rAP). This is the first general electrochemical access to diazene radicals. The in situ-formed nitrogen radical engages aryl diazoacetates via radical coupling after dinitrogen extrusion (via blue LED), delivering a diverse library of N-acyl hydrazones. The same radical intermediate undergoes a Michael-type conjugate addition to N-aryl maleimides, affording imide-linked hydrazine derivatives, thereby establishing a rare example of radical divergence from a single electrochemically generated intermediate. The method is broadly applicable across 9 carbazate classes affording 35 products, including drug-derived motifs, and proceeds under mild conditions in the absence of external reductants or catalysts. Together, these results introduce a sustainable, redox-economical strategy for N-C bond construction and expand the synthetic utility of hydrazine radicals in electroorganic chemistry.
{"title":"A Divergent Electrochemical Platform for Diazene Radical Generation and C–N Coupling Reactions","authors":"Roopam Pandey, Suchismita Rath, Yashika Tyagi, Shivani Jadoni, Tejas Prabakar, Shreemad Patel, Debajit Maiti, Subhabrata Sen","doi":"10.1039/d6qo00078a","DOIUrl":"https://doi.org/10.1039/d6qo00078a","url":null,"abstract":"The development of sustainable methods for controlled C-N bond formation remains a central challenge in modern synthesis. Here we report an operationally simple, catalyst-free and acid/base-free electrochemical platform that enables the direct single-electron activation of N-carbazates to generate a versatile diazene-centred radical under direct current (DC) or rapid alternating polarity current (rAP). This is the first general electrochemical access to diazene radicals. The in situ-formed nitrogen radical engages aryl diazoacetates via radical coupling after dinitrogen extrusion (via blue LED), delivering a diverse library of N-acyl hydrazones. The same radical intermediate undergoes a Michael-type conjugate addition to N-aryl maleimides, affording imide-linked hydrazine derivatives, thereby establishing a rare example of radical divergence from a single electrochemically generated intermediate. The method is broadly applicable across 9 carbazate classes affording 35 products, including drug-derived motifs, and proceeds under mild conditions in the absence of external reductants or catalysts. Together, these results introduce a sustainable, redox-economical strategy for N-C bond construction and expand the synthetic utility of hydrazine radicals in electroorganic chemistry.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"68 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358784","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}
Fengjuan Ma, Qing Sun, Jingxin Hu, Xin Cheng, Huiwen Zheng, Lei Zhou, Xin Lu, Yidong Luo, Ren-Jie Song
Bimetallic catalysis offers enhanced reactivity, selectivity, and cooperative effects compared to traditional monometallic catalysis. However, the detailed understanding of coordination and metal interactions in such bimetallic systems is still elusive. Herein, we employ density functional theory (DFT) calculations to systematically investigate the reaction mechanism and selectivity of a gold/copper bimetallic system in the tandem cyclization reaction of pyridylhomopropargylic alcohol and propargyl alcohol. Our findings unveil a distinct "handshake relay" mechanism: In the initial cycle, gold activates the substrate pyridylhomopropargylic alcohol via π-acid activation, facilitating a 5-endo-dig cyclization to generate a pivotal 2,3-dihydrofuran intermediate. In the subsequent cycle, gold activates propargyl alcohol to enable intermolecular carbon-carbon coupling, dehydration and cyclization. Copper then takes over through coordination, dramatically lowering the energy barrier for the Friedel-Crafts cyclization and promoting H2 elimination to ultimately yield the polycyclic dihydrobenzofuran product. This study not only clarifies the dynamic transition of active metal centers during bimetallic relay catalysis but also elucidates the distinct roles of gold and copper at different stages of the reaction. Our findings significantly advance the understanding of synergistic catalysis in gold/copper systems, providing valuable insights into the efficient synthesis of complex heterocycles and overcoming the limitations of traditional monometallic catalysis.
{"title":"Unveiling the mechanisms of gold/copper bimetallic catalysis in the synthesis of complex heterocyclic compounds","authors":"Fengjuan Ma, Qing Sun, Jingxin Hu, Xin Cheng, Huiwen Zheng, Lei Zhou, Xin Lu, Yidong Luo, Ren-Jie Song","doi":"10.1039/d5qo01639h","DOIUrl":"https://doi.org/10.1039/d5qo01639h","url":null,"abstract":"Bimetallic catalysis offers enhanced reactivity, selectivity, and cooperative effects compared to traditional monometallic catalysis. However, the detailed understanding of coordination and metal interactions in such bimetallic systems is still elusive. Herein, we employ density functional theory (DFT) calculations to systematically investigate the reaction mechanism and selectivity of a gold/copper bimetallic system in the tandem cyclization reaction of pyridylhomopropargylic alcohol and propargyl alcohol. Our findings unveil a distinct \"handshake relay\" mechanism: In the initial cycle, gold activates the substrate pyridylhomopropargylic alcohol via π-acid activation, facilitating a 5-endo-dig cyclization to generate a pivotal 2,3-dihydrofuran intermediate. In the subsequent cycle, gold activates propargyl alcohol to enable intermolecular carbon-carbon coupling, dehydration and cyclization. Copper then takes over through coordination, dramatically lowering the energy barrier for the Friedel-Crafts cyclization and promoting H2 elimination to ultimately yield the polycyclic dihydrobenzofuran product. This study not only clarifies the dynamic transition of active metal centers during bimetallic relay catalysis but also elucidates the distinct roles of gold and copper at different stages of the reaction. Our findings significantly advance the understanding of synergistic catalysis in gold/copper systems, providing valuable insights into the efficient synthesis of complex heterocycles and overcoming the limitations of traditional monometallic catalysis.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"53 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360169","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}
Vaibhav Ramachandra Pansare, Sreelakshmi N, Nagaraju Barsu
The direct C–H alkylation of nitrogen-containing heterocycles is a valuable and widely pursued transformation due to the importance of these scaffolds in pharmaceuticals and bioactive natural products. In this study, we report a general and efficient Fe(acac)₃/TBHP-catalyzed strategy for C(sp²)–H alkylation of a variety of N-heterocyclic frameworks, including pyrazinones and azauracils derivatives. Utilizing readily available ethers and aryl alkanes as alkylating agents, the protocol exhibits broad substrate scope, excellent tolerance to diverse functional groups, and practical scalability. Mechanistic studies, including radical scavenging experiments, suggest a radical-mediated path involved in the transformation.
{"title":"Site-selective iron-catalyzed C-H alkylation of pyrazinones, azauracils and quinoxalinones","authors":"Vaibhav Ramachandra Pansare, Sreelakshmi N, Nagaraju Barsu","doi":"10.1039/d6qo00044d","DOIUrl":"https://doi.org/10.1039/d6qo00044d","url":null,"abstract":"The direct C–H alkylation of nitrogen-containing heterocycles is a valuable and widely pursued transformation due to the importance of these scaffolds in pharmaceuticals and bioactive natural products. In this study, we report a general and efficient Fe(acac)₃/TBHP-catalyzed strategy for C(sp²)–H alkylation of a variety of N-heterocyclic frameworks, including pyrazinones and azauracils derivatives. Utilizing readily available ethers and aryl alkanes as alkylating agents, the protocol exhibits broad substrate scope, excellent tolerance to diverse functional groups, and practical scalability. Mechanistic studies, including radical scavenging experiments, suggest a radical-mediated path involved in the transformation.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"4 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147360171","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}
Bao-Gui Cai, Li-Hua Zhang, Yang Xie, Qiong Zhang, Jun Xuan
The visible-light-induced ring-opening of 2H-azirines has primarily focused on the selective cleavage of individual bonds, such as C–C, C–N, or C=N. However, simultaneous cleavage of multiple bonds, such as both C–C and C–N, under photochemical conditions has not been reported, and the ability to control distinct ring-opening pathways in a divergent manner remains underexplored. Herein, we report a visible-light-promoted, base-assisted cycloaddition reaction between 2H-azirines and hydrazonyl chlorides via in situ formation of an EDA complex. This catalyst-free transformation enables the selective formation of either 1,3,5-triazines or imidazoles, depending on the substitution pattern of the 2H-azirine. Notably, preliminary evaluation of the resulting imidazole derivatives revealed promising optical properties, suggesting potential applications in photonic materials. This work provides a practical and sustainable platform for the construction of diverse nitrogen-containing heterocycles from simple and readily available building blocks.
可见光诱导的2H-azirines开环主要集中在单个键的选择性切割上，如C - C， C - N或C=N。然而，在光化学条件下同时切割多个键（如C-C和C-N）的研究尚未见报道，以不同的方式控制不同开环途径的能力仍未得到充分探索。在这里，我们报道了一个可见光促进的，碱辅助的环加成反应在2h -氮嘧啶和肼酰氯之间通过原位形成一个EDA配合物。根据2h -氮嘧啶的取代模式，这种无催化剂转化可以选择性地形成1,3,5-三嗪或咪唑。值得注意的是，对所得到的咪唑衍生物的初步评价显示出了良好的光学性质，表明了在光子材料中的潜在应用。这项工作为从简单易得的构建块构建多种含氮杂环提供了一个实用和可持续的平台。
{"title":"Tunable Ring-Opening of 2H-Azirines via Visible-Light-Driven Novel Selective C-C/C-N or C=N Bond Cleavage","authors":"Bao-Gui Cai, Li-Hua Zhang, Yang Xie, Qiong Zhang, Jun Xuan","doi":"10.1039/d6qo00168h","DOIUrl":"https://doi.org/10.1039/d6qo00168h","url":null,"abstract":"The visible-light-induced ring-opening of 2H-azirines has primarily focused on the selective cleavage of individual bonds, such as C–C, C–N, or C=N. However, simultaneous cleavage of multiple bonds, such as both C–C and C–N, under photochemical conditions has not been reported, and the ability to control distinct ring-opening pathways in a divergent manner remains underexplored. Herein, we report a visible-light-promoted, base-assisted cycloaddition reaction between 2H-azirines and hydrazonyl chlorides via in situ formation of an EDA complex. This catalyst-free transformation enables the selective formation of either 1,3,5-triazines or imidazoles, depending on the substitution pattern of the 2H-azirine. Notably, preliminary evaluation of the resulting imidazole derivatives revealed promising optical properties, suggesting potential applications in photonic materials. This work provides a practical and sustainable platform for the construction of diverse nitrogen-containing heterocycles from simple and readily available building blocks.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"14 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147358785","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}
Lei Cao, Jiarui Chang, Xi-Meng Chen, Yan-Na Ma, Xuenian Chen
Compared with an enormous amount of reactions of the B-H bond of the Lewis base BH3 adducts, the reactions of the B-H bond of the multinuclear boranes have been less studied, probably relative to the distinct nature of the B−H bond in the BH3 moiety and in the multinuclear boranes. Herein, we report a protocol for the highly regioselective functionalization of triborane, the oldest multinuclear borane, via copper-catalyzed B−H bond insertion reactions with diazos. A variety of beneficial organoboron compounds are synthesized with generally high yields, broad substrate versatility, and robust functional group compatibility under gentle reaction conditions. Notably, the B−H bond in the reactions is highly selective, located at the bottom B(2) position of the triboranes, leading to the formation of compounds with boron-stereogenic centers. The B(2)-substituted triborane product can continue to react with α-Diazos to form both bottom B(2,3)-disubstituted triborane products. Moreover, this synthesis method is also applicable to ¹⁰B-labeled Lewis base-¹⁰B3H7 adduct to synthesize ‘targeted drugs’ suitable for boron neutron capture therapy (BNCT).
{"title":"Copper-catalyzed B–H bond insertion reaction of triboranes (L·B3H7) with diazo compounds","authors":"Lei Cao, Jiarui Chang, Xi-Meng Chen, Yan-Na Ma, Xuenian Chen","doi":"10.1039/d6qo00098c","DOIUrl":"https://doi.org/10.1039/d6qo00098c","url":null,"abstract":"Compared with an enormous amount of reactions of the B-H bond of the Lewis base BH3 adducts, the reactions of the B-H bond of the multinuclear boranes have been less studied, probably relative to the distinct nature of the B−H bond in the BH3 moiety and in the multinuclear boranes. Herein, we report a protocol for the highly regioselective functionalization of triborane, the oldest multinuclear borane, via copper-catalyzed B−H bond insertion reactions with diazos. A variety of beneficial organoboron compounds are synthesized with generally high yields, broad substrate versatility, and robust functional group compatibility under gentle reaction conditions. Notably, the B−H bond in the reactions is highly selective, located at the bottom B(2) position of the triboranes, leading to the formation of compounds with boron-stereogenic centers. The B(2)-substituted triborane product can continue to react with α-Diazos to form both bottom B(2,3)-disubstituted triborane products. Moreover, this synthesis method is also applicable to ¹⁰B-labeled Lewis base-¹⁰B3H7 adduct to synthesize ‘targeted drugs’ suitable for boron neutron capture therapy (BNCT).","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"1 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147334522","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}
Xin Guo, Guoliang Pu, Long Xiao, Jiarui Liang, Hang Zhang, Yu Chen, Yang Huang, Qiuli Yao, Chun-Yang He
Here, we report a EtAlCl2-promoted thiolation of trifluoromethyl alkenes, which leads to the complete substitution of all three fluorine atoms and affords trisubstituted products. Although the transformation proceeds through a three-step sequence, it maintains high efficiency and delivers the target product in good to excellent yields. Mechanistic studies indicate that the reaction initially forms a gem-difluoroalkene intermediate. The newly introduced thioether group then activates the remaining C-F bonds, thereby facilitating subsequent substitution to afford the trisubstituted products.
{"title":"EtAlCl2 -Promoted Defluorinative Thiolation of α-Trifluoromethyl Alkenes","authors":"Xin Guo, Guoliang Pu, Long Xiao, Jiarui Liang, Hang Zhang, Yu Chen, Yang Huang, Qiuli Yao, Chun-Yang He","doi":"10.1039/d6qo00011h","DOIUrl":"https://doi.org/10.1039/d6qo00011h","url":null,"abstract":"Here, we report a EtAlCl2-promoted thiolation of trifluoromethyl alkenes, which leads to the complete substitution of all three fluorine atoms and affords trisubstituted products. Although the transformation proceeds through a three-step sequence, it maintains high efficiency and delivers the target product in good to excellent yields. Mechanistic studies indicate that the reaction initially forms a gem-difluoroalkene intermediate. The newly introduced thioether group then activates the remaining C-F bonds, thereby facilitating subsequent substitution to afford the trisubstituted products.","PeriodicalId":97,"journal":{"name":"Organic Chemistry Frontiers","volume":"35 1","pages":""},"PeriodicalIF":5.4,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147330082","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}
Hong Ji, Haifeng Qiao, Boyi Wang, Tianyu Lu, Weixing Chang, Lingyan Liu, Jing Li
The construction of carbon-fluorine bond has always remained challenging. This work described a two-component 1,2carbofluorination bifunctionalization of unactivated alkenes through a free radical relay process. The N-fluorobenzamide was firstly used as a unique carbofluoro-bifunctional molecule to attack the unactivated alkenes with the concomitant formation of C-C bond and C-F bond. This reaction initially underwent a N-F bond homolysis to give nitrogen free radical, with the subsequent 1,5-H atom transfer to generate the remote benzylic carbon free radical, and further attacked the alkene to render new alkyl free radical, and followed by single electron transfer of active metal copper species, finally, a series of β-fluoroamides was obtained in moderate yields. This reaction also features excellent atom economy without any atom lost, mild reaction conditions and facile operation.
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