Pub Date : 2025-12-15Epub Date: 2025-10-10DOI: 10.1016/j.tetlet.2025.155848
John Kim, Anna Page, Ryan T. Vanderlinden, Ryan E. Looper
Chiral α-amino- and α-amidoboronates are established pharmacophores in numerous drugs and drug candidates, however, methods to prepare this motif are limited. We report the preparation of cyclic α-amino boronates via a three-component coupling reaction of salicylaldehydes, tetrahydroxydiboron, and chiral amines. Deploying 1,2-aminoalcohol and aminoacid derivatives delivers a structurally diverse set of cyclic α-aminoboronates. Moderate to high diastereoselectivity is noted both at the newly forged carbon‑boron bond and at the tetrahedral boron center.
{"title":"A diastereoselective preparation of cyclic α-aminoboronates","authors":"John Kim, Anna Page, Ryan T. Vanderlinden, Ryan E. Looper","doi":"10.1016/j.tetlet.2025.155848","DOIUrl":"10.1016/j.tetlet.2025.155848","url":null,"abstract":"<div><div>Chiral α-amino- and α-amidoboronates are established pharmacophores in numerous drugs and drug candidates, however, methods to prepare this motif are limited. We report the preparation of cyclic α-amino boronates via a three-component coupling reaction of salicylaldehydes, tetrahydroxydiboron, and chiral amines. Deploying 1,2-aminoalcohol and aminoacid derivatives delivers a structurally diverse set of cyclic α-aminoboronates. Moderate to high diastereoselectivity is noted both at the newly forged carbon‑boron bond and at the tetrahedral boron center.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155848"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-02DOI: 10.1016/j.tetlet.2025.155829
Man Jiang , Xue Sheng , Yu Luo, Hai-Lei Cui
An efficient construction of highly substituted pyrrolo[2,1-a]isoquinoline derivatives has been reached with tetrahydroisoquinolines, aromatic aldehydes and activated olefins through condensation/cycloaddition/aromatization cascade in the presence of copper salts as catalyst. The current approach features the direct use of unactivated aldehydes and high efficiency. Interestingly, the obtained pyrrolo[2,1-a]isoquinolines can be easily modified through reduction, nitration and amidation.
{"title":"Copper-catalyzed synthesis of pyrrolo[2,1-a]isoquinolines through condensation/cycloaddition/aromatization cascade","authors":"Man Jiang , Xue Sheng , Yu Luo, Hai-Lei Cui","doi":"10.1016/j.tetlet.2025.155829","DOIUrl":"10.1016/j.tetlet.2025.155829","url":null,"abstract":"<div><div>An efficient construction of highly substituted pyrrolo[2,1-<em>a</em>]isoquinoline derivatives has been reached with tetrahydroisoquinolines, aromatic aldehydes and activated olefins through condensation/cycloaddition/aromatization cascade in the presence of copper salts as catalyst. The current approach features the direct use of unactivated aldehydes and high efficiency. Interestingly, the obtained pyrrolo[2,1-<em>a</em>]isoquinolines can be easily modified through reduction, nitration and amidation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155829"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-14DOI: 10.1016/j.tetlet.2025.155853
Yasufumi Fuchi, Yoshiyuki Hari
In solid-phase synthesis of oligonucleotides (ONs), not only the target ON but also undesired byproducts, including short-length ONs, are produced. However, because these ONs possess similar physicochemical properties, they are often difficult to separate using chromatography such as reversed-phase HPLC. To facilitate the separation of the target ON from undesired ONs, the purification handle 4,4′-dimethoxytrityl (DMTr) group has been utilized. Until now, several types of purification handles containing lipophilic groups, in addition to the DMTr group, have been reported. In this paper, recent advances and methodologies related to the purification handles for ON purification are summarized.
{"title":"Recent advances related to purification handles for oligonucleotide separation","authors":"Yasufumi Fuchi, Yoshiyuki Hari","doi":"10.1016/j.tetlet.2025.155853","DOIUrl":"10.1016/j.tetlet.2025.155853","url":null,"abstract":"<div><div>In solid-phase synthesis of oligonucleotides (ONs), not only the target ON but also undesired byproducts, including short-length ONs, are produced. However, because these ONs possess similar physicochemical properties, they are often difficult to separate using chromatography such as reversed-phase HPLC. To facilitate the separation of the target ON from undesired ONs, the purification handle 4,4′-dimethoxytrityl (DMTr) group has been utilized. Until now, several types of purification handles containing lipophilic groups, in addition to the DMTr group, have been reported. In this paper, recent advances and methodologies related to the purification handles for ON purification are summarized.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155853"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-04DOI: 10.1016/j.tetlet.2025.155841
Jie Zhen Shi , Yan Li Zhang , Jin Hua Yu , Da Mei Wang , Dong Gan , Zhong Tao Ding
Two new fungal alkaloids, arthriniumperazine A (1) and arthriniumperazine B (2), along with the known mycoediketopiperazine (3), were isolated from the endophytic fungus Arthrinium malaysianum DD-1. Notably, this class of fungal alkaloids is scarcely reported, with only compound 3 being previously documented in the literature. The planar structures of 1 and 2 were elucidated through comprehensive spectroscopic analyses, including 1H/13C NMR and HR-ESI-MS. Their absolute configurations were unambiguously determined by comparative ECD calculations. In bioactivity assays, compound 2 exhibited weak α-glucosidase inhibitory activity (18.95 ± 3.77 %, n = 3). For antimicrobial evaluation, compound 1 showed broad-spectrum activity with consistent MICs of 26.60 μg/mL against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli. Compound 2 exhibited selective inhibitory effects against Escherichia coli (26.60 μg/mL) and Staphylococcus aureus (26.60 μg/mL) in the broth microdilution assay, while displaying no significant inhibition against Bacillus subtilis.
{"title":"Two novel fungal alkaloids were isolated from Arthrinium malaysianum and their bioactivities","authors":"Jie Zhen Shi , Yan Li Zhang , Jin Hua Yu , Da Mei Wang , Dong Gan , Zhong Tao Ding","doi":"10.1016/j.tetlet.2025.155841","DOIUrl":"10.1016/j.tetlet.2025.155841","url":null,"abstract":"<div><div>Two new fungal alkaloids, arthriniumperazine A (<strong>1</strong>) and arthriniumperazine B (<strong>2</strong>), along with the known mycoediketopiperazine (<strong>3</strong>), were isolated from the endophytic fungus <em>Arthrinium</em> malaysianum DD-1. Notably, this class of fungal alkaloids is scarcely reported, with only compound <strong>3</strong> being previously documented in the literature. The planar structures of <strong>1</strong> and <strong>2</strong> were elucidated through comprehensive spectroscopic analyses, including <sup>1</sup>H/<sup>13</sup>C NMR and HR-ESI-MS. Their absolute configurations were unambiguously determined by comparative ECD calculations. In bioactivity assays, compound <strong>2</strong> exhibited weak α-glucosidase inhibitory activity (18.95 ± 3.77 %, <em>n</em> = 3). For antimicrobial evaluation, compound <strong>1</strong> showed broad-spectrum activity with consistent MICs of 26.60 μg/mL against <em>Bacillus subtilis</em>, <em>Staphylococcus aureus</em>, and <em>Escherichia coli</em>. Compound <strong>2</strong> exhibited selective inhibitory effects against <em>Escherichia coli</em> (26.60 μg/mL) and <em>Staphylococcus aureus</em> (26.60 μg/mL) in the broth microdilution assay, while displaying no significant inhibition against <em>Bacillus subtilis</em>.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155841"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-09-18DOI: 10.1016/j.tetlet.2025.155830
Zhihua Chen , Jincheng Zhu , Mengxing Wang , Qinglin Wu , Yichun Xu , Lei Cui , Kewen Zheng
The widespread misuse of antibiotics has accelerated bacterial evolution, precipitating a global antimicrobial resistance (AMR) crisis. Photodynamic therapy (PDT) has recently emerged as a promising alternative due to its non-invasiveness, cost-effectiveness and broad-spectrum antimicrobial activity. Boron-dipyrromethene (BODIPY) derivatives constitute a promising class of organic photosensitizers with experimentally verified photodynamic activity. However, conventional BODIPY-based photosensitizers face significant limitations: their inherent hydrophobicity reduces reactive oxygen species (ROS) generation efficiency, diminishes antimicrobial coverage, and may paradoxically promote resistance development. Furthermore, their exclusive production of Type I PDT, without complementary Type II mechanisms, substantially restricts their therapeutic potential. Herein, a series of photosensitizers (PSs) with antibacterial properties was developed by leveraging electron push-pull systems coupled with heavy-atom effects. In addition to enhance the aqueous solubility of photosensitizers, three types were encapsulated into liposomes via the thin film hydration method. Benefiting from sufficient molecular rotors and high electronegativity of fluorine, the developed BDP-F Lips exhibit superior ROS generation capacity under laser irradiation, concurrently producing both Type I and Type II PDT, thereby demonstrating excellent antibacterial efficacy.
{"title":"Dual-type photodynamic therapy enabled by fluorinated BODIPY-liposome hybrids for enhanced antibacterial efficacy","authors":"Zhihua Chen , Jincheng Zhu , Mengxing Wang , Qinglin Wu , Yichun Xu , Lei Cui , Kewen Zheng","doi":"10.1016/j.tetlet.2025.155830","DOIUrl":"10.1016/j.tetlet.2025.155830","url":null,"abstract":"<div><div>The widespread misuse of antibiotics has accelerated bacterial evolution, precipitating a global antimicrobial resistance (AMR) crisis. Photodynamic therapy (PDT) has recently emerged as a promising alternative due to its non-invasiveness, cost-effectiveness and broad-spectrum antimicrobial activity. Boron-dipyrromethene (BODIPY) derivatives constitute a promising class of organic photosensitizers with experimentally verified photodynamic activity. However, conventional BODIPY-based photosensitizers face significant limitations: their inherent hydrophobicity reduces reactive oxygen species (ROS) generation efficiency, diminishes antimicrobial coverage, and may paradoxically promote resistance development. Furthermore, their exclusive production of Type I PDT, without complementary Type II mechanisms, substantially restricts their therapeutic potential. Herein, a series of photosensitizers (PSs) with antibacterial properties was developed by leveraging electron push-pull systems coupled with heavy-atom effects. In addition to enhance the aqueous solubility of photosensitizers, three types were encapsulated into liposomes via the thin film hydration method. Benefiting from sufficient molecular rotors and high electronegativity of fluorine, the developed BDP-F Lips exhibit superior ROS generation capacity under laser irradiation, concurrently producing both Type I and Type II PDT, thereby demonstrating excellent antibacterial efficacy.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155830"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145128257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-15DOI: 10.1016/j.tetlet.2025.155864
Gyeong Han Jeong , Tae Hoon Kim
(−)-Epigallocatechin (EGC) and sesamol hybridized products 1–3 were successfully synthesized by atmospheric pressure (ATP) plasma treatment. The chemical structures of newly hybridized products were determined by interpretation of spectroscopic data (NMR and FABMS), with the absolute stereochemistry being established by analysis of the circular dichroism (CD) spectra. The unprecedented hybrid structure sesacachin A (1) exhibited enhanced anti-glycation capacities toward the formation of advanced glycation end products (AGEs) and hydroxyl radical scavenging compared to the original (−)-EGC and sesamol. A novel hybrid product, sesacachin A (1), represents a promising subclass of anti-glycation candidates that needs further investigation.
{"title":"Plasma-induced hybridization based on (−)-epigallocatechin as a potent anti-glycation agents","authors":"Gyeong Han Jeong , Tae Hoon Kim","doi":"10.1016/j.tetlet.2025.155864","DOIUrl":"10.1016/j.tetlet.2025.155864","url":null,"abstract":"<div><div>(−)-Epigallocatechin (EGC) and sesamol hybridized products <strong>1</strong>–<strong>3</strong> were successfully synthesized by atmospheric pressure (ATP) plasma treatment. The chemical structures of newly hybridized products were determined by interpretation of spectroscopic data (NMR and FABMS), with the absolute stereochemistry being established by analysis of the circular dichroism (CD) spectra. The unprecedented hybrid structure sesacachin A (<strong>1</strong>) exhibited enhanced anti-glycation capacities toward the formation of advanced glycation end products (AGEs) and hydroxyl radical scavenging compared to the original (−)-EGC and sesamol. A novel hybrid product, sesacachin A (<strong>1</strong>), represents a promising subclass of anti-glycation candidates that needs further investigation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155864"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-08DOI: 10.1016/j.tetlet.2025.155850
Mir Mohd Ikhlaq , Nguyen Ngoc Thanh Luan , Takuya Okada , Naoki Toyooka
Gosodesmine (1) is an indolizidine alkaloid that was isolated and structurally determined in 2020, but its absolute stereochemistry remained unknown. We synthesized 1 from Boc-L-β-homoproline (4) and compared the optical rotations of our synthesized Gosodesmine with the natural Gosodesmine. Based on the reported values, we determined that the absolute stereochemistry of 1 is the R-configuration. Additionally, we demonstrated using HPLC that racemization did not occur during our synthesis.
{"title":"Synthesis and determination of absolute stereochemistry of Gosodesmine","authors":"Mir Mohd Ikhlaq , Nguyen Ngoc Thanh Luan , Takuya Okada , Naoki Toyooka","doi":"10.1016/j.tetlet.2025.155850","DOIUrl":"10.1016/j.tetlet.2025.155850","url":null,"abstract":"<div><div>Gosodesmine (<strong>1</strong>) is an indolizidine alkaloid that was isolated and structurally determined in 2020, but its absolute stereochemistry remained unknown. We synthesized <strong>1</strong> from Boc-L-β-homoproline (<strong>4</strong>) and compared the optical rotations of our synthesized Gosodesmine with the natural Gosodesmine. Based on the reported values, we determined that the absolute stereochemistry of <strong>1</strong> is the <em>R</em>-configuration. Additionally, we demonstrated using HPLC that racemization did not occur during our synthesis.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155850"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-10-07DOI: 10.1016/j.tetlet.2025.155838
Babak Mahjour , Rui Zhang , Andrew Outlaw , Felix Katzenburg , Mohamed Abdelalim , Xueying Zhang , Alexander S. Harmata , Tim Cernak
The exploration of chemical space is fundamentally shaped by the availability of commercial building blocks. A common strategy in drug discovery involves attaching these building blocks – such as amines, acids, alcohols, aldehydes, halides, and boronates – to core pharmacophores using robust and well-established reactions like amide coupling, Buchwald-Hartwig coupling, Fischer esterification, and Suzuki coupling. This systematic approach underpins much of modern medicinal chemistry. However, advances in reaction methodology now offer the opportunity to repurpose these familiar building blocks in novel transformations, including of reaction transformations that are plausible but may not have been developed yet. Here, we use cheminformatics to identify high-value building block classes based on both their commercial availability and their potential to access drug-like chemical space. These analyses guide the prioritization of building blocks for reaction development efforts. Finally, we showcase several experimental case studies that demonstrate new reactivities between prioritized building blocks, highlighting the potential for navigating deeper into chemical space.
{"title":"A reaction enumeration analysis of building blocks to target novel coupling methods","authors":"Babak Mahjour , Rui Zhang , Andrew Outlaw , Felix Katzenburg , Mohamed Abdelalim , Xueying Zhang , Alexander S. Harmata , Tim Cernak","doi":"10.1016/j.tetlet.2025.155838","DOIUrl":"10.1016/j.tetlet.2025.155838","url":null,"abstract":"<div><div>The exploration of chemical space is fundamentally shaped by the availability of commercial building blocks. A common strategy in drug discovery involves attaching these building blocks – such as amines, acids, alcohols, aldehydes, halides, and boronates – to core pharmacophores using robust and well-established reactions like amide coupling, Buchwald-Hartwig coupling, Fischer esterification, and Suzuki coupling. This systematic approach underpins much of modern medicinal chemistry. However, advances in reaction methodology now offer the opportunity to repurpose these familiar building blocks in novel transformations, including of reaction transformations that are plausible but may not have been developed yet. Here, we use cheminformatics to identify high-value building block classes based on both their commercial availability and their potential to access drug-like chemical space. These analyses guide the prioritization of building blocks for reaction development efforts. Finally, we showcase several experimental case studies that demonstrate new reactivities between prioritized building blocks, highlighting the potential for navigating deeper into chemical space.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155838"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-09-24DOI: 10.1016/j.tetlet.2025.155840
Tsukasa Inishi, Yuta Nakamura, Toshitaka Okamura, Takashi Nishikata
Catalyst-free 1,4-addition of 1-alkenylboronic acids to enones is reported. Contrary to conventional methodologies requiring Lewis acids or transition metals, we discovered that 1-alkenylboronic acids intrinsically mediate efficient conjugate additions (up to 95 % yield) without external catalysts. This reactivity stems from a dual activation mode: the boronic acid simultaneously acts as a nucleophile and a Lewis acidic activator, enhancing the electrophilicity of the enone carbonyl group. While brominated chalcones exhibited moderately reduced reactivity, the reaction proceeds cleanly with broad substrate tolerance and no observable byproducts. This method eliminates the need for metal catalysts—exemplified by the superior performance over cationic iron complexes (78 % vs. 95 % yield)—aligning with green chemistry principles through reduced resource consumption and waste generation. Our findings unveil an unprecedented role for boronic acids as self-sufficient mediators, offering a sustainable paradigm for ketone synthesis.
报道了1-烯基硼酸在烯酮中的无催化剂1,4加成反应。与需要Lewis酸或过渡金属的传统方法相反，我们发现1-烯基硼酸本质上介导有效的共轭添加（高达95%的产率）而无需外部催化剂。这种反应性源于双重激活模式：硼酸同时作为亲核试剂和路易斯酸激活剂，增强烯酮羰基的亲电性。虽然溴化查尔酮表现出适度降低的反应活性，但反应进行干净，具有广泛的底物耐受性，没有可观察到的副产物。这种方法消除了对金属催化剂的需求，阳离子铁配合物的性能优于阳离子铁配合物（产率78% vs 95%），通过减少资源消耗和废物产生，符合绿色化学原则。我们的发现揭示了硼酸作为自给自足介质的前所未有的作用，为酮合成提供了一个可持续的范例。
{"title":"Catalyst-free conjugate addition of 1-alkenylboronic acids to enones: a self-mediated sustainable protocol","authors":"Tsukasa Inishi, Yuta Nakamura, Toshitaka Okamura, Takashi Nishikata","doi":"10.1016/j.tetlet.2025.155840","DOIUrl":"10.1016/j.tetlet.2025.155840","url":null,"abstract":"<div><div>Catalyst-free 1,4-addition of 1-alkenylboronic acids to enones is reported. Contrary to conventional methodologies requiring Lewis acids or transition metals, we discovered that 1-alkenylboronic acids intrinsically mediate efficient conjugate additions (up to 95 % yield) without external catalysts. This reactivity stems from a dual activation mode: the boronic acid simultaneously acts as a nucleophile and a Lewis acidic activator, enhancing the electrophilicity of the enone carbonyl group. While brominated chalcones exhibited moderately reduced reactivity, the reaction proceeds cleanly with broad substrate tolerance and no observable byproducts. This method eliminates the need for metal catalysts—exemplified by the superior performance over cationic iron complexes (78 % vs. 95 % yield)—aligning with green chemistry principles through reduced resource consumption and waste generation. Our findings unveil an unprecedented role for boronic acids as self-sufficient mediators, offering a sustainable paradigm for ketone synthesis.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155840"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-15Epub Date: 2025-09-20DOI: 10.1016/j.tetlet.2025.155834
Xiu Liu , Hongjun Chen , Chenzhong Jin , Longzhi Zhu , Biquan Xiong
An efficient and atom-economical phosphoric acid-catalyzed amidation of para-quinone methides (p-QMs) with acetonitrile has been developed under mild conditions. Water serves as the sole source of both hydrogen and oxygen atoms, enabling 100 % atom economy in amide bond formation. The reaction exhibits excellent generality across a broad spectrum of electronically and sterically diverse p-QMs, facilitating efficient and highly regioselective synthesis of synthetically valuable N-diarylmethyl-substituted acetamides in good to excellent yields. Step-by-step control experiments and competitive deuterium-labeling KIE studies elucidated the reaction pathway and led to a plausible mechanism based on cumulative experimental evidences.
{"title":"Phosphoric acid-catalyzed regioselective amidation of para-quinone methides with acetonitrile","authors":"Xiu Liu , Hongjun Chen , Chenzhong Jin , Longzhi Zhu , Biquan Xiong","doi":"10.1016/j.tetlet.2025.155834","DOIUrl":"10.1016/j.tetlet.2025.155834","url":null,"abstract":"<div><div>An efficient and atom-economical phosphoric acid-catalyzed amidation of <em>para</em>-quinone methides (<em>p</em>-QMs) with acetonitrile has been developed under mild conditions. Water serves as the sole source of both hydrogen and oxygen atoms, enabling 100 % atom economy in amide bond formation. The reaction exhibits excellent generality across a broad spectrum of electronically and sterically diverse <em>p</em>-QMs, facilitating efficient and highly regioselective synthesis of synthetically valuable <em>N</em>-diarylmethyl-substituted acetamides in good to excellent yields. Step-by-step control experiments and competitive deuterium-labeling KIE studies elucidated the reaction pathway and led to a plausible mechanism based on cumulative experimental evidences.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155834"},"PeriodicalIF":1.5,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145157569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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