Pub 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":"2025-10-08","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}
A simple and efficient method for the construction of symmetrical and unsymmetrical diaryl sulfones has been developed. Herein, Cu(OAc)2-catalyzed oxidative cross-coupling of aryl sulfonyl hydrazides and aryl hydrazine easily afforded the diaryl sulfones in the presence of K2CO3 base and DMSO medium. Notably, a variety of diaryl sulfone derivatives have been synthesized in moderate to good yields.
{"title":"Copper-catalyzed cross-coupling of sulfonyl hydrazides with aryl hydrazines to synthesize diaryl sulfones","authors":"E.V. Venkat Shivaji Ramarao , Jayshree Solanke , Rana Chatterjee , Rambabu Dandela","doi":"10.1016/j.tetlet.2025.155845","DOIUrl":"10.1016/j.tetlet.2025.155845","url":null,"abstract":"<div><div>A simple and efficient method for the construction of symmetrical and unsymmetrical diaryl sulfones has been developed. Herein, Cu(OAc)<sub>2</sub>-catalyzed oxidative cross-coupling of aryl sulfonyl hydrazides and aryl hydrazine easily afforded the diaryl sulfones in the presence of K<sub>2</sub>CO<sub>3</sub> base and DMSO medium. Notably, a variety of diaryl sulfone derivatives have been synthesized in moderate to good yields.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"174 ","pages":"Article 155845"},"PeriodicalIF":1.5,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145335017","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 : 2025-10-07DOI: 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":"2025-10-07","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 : 2025-10-06DOI: 10.1016/j.tetlet.2025.155844
Manisha Kundu, Rajat Ghosh, Shital K. Chattopadhyay
A one-pot Pd-catalyzed Larock-type [3 + 3]-annulation of an 2-iodoarene with 2-amidoacrylates has been developed which provides an easy access to 1,3-disubstituted-1,2-dihydroisoquinoline derivatives in good yields (54–71 %). The process involves Mizoroki-Heck type arylation as the first step followed by spontaneous intramolecular aza-Michael reaction mediated ring closure.
{"title":"Tandem Mizoroki-Heck arylation and Aza-Michael reaction: A rapid access to 1,3-Disubstituted-1,2-dihydroisoquinoline derivatives","authors":"Manisha Kundu, Rajat Ghosh, Shital K. Chattopadhyay","doi":"10.1016/j.tetlet.2025.155844","DOIUrl":"10.1016/j.tetlet.2025.155844","url":null,"abstract":"<div><div>A one-pot Pd-catalyzed Larock-type [3 + 3]-annulation of an 2-iodoarene with 2-amidoacrylates has been developed which provides an easy access to 1,3-disubstituted-1,2-dihydroisoquinoline derivatives in good yields (54–71 %). The process involves Mizoroki-Heck type arylation as the first step followed by spontaneous intramolecular aza-Michael reaction mediated ring closure.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155844"},"PeriodicalIF":1.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264130","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 : 2025-10-04DOI: 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":"2025-10-04","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 : 2025-10-04DOI: 10.1016/j.tetlet.2025.155846
Xiaoxu Gao , Liting Xu , Peixin Shi, Jiawei Chen, Zhaohai Qin, Bin Fu
An efficient approach to dihydroindole scaffold was developed via [4 + 1] annulation from 2-amino-β-nitrostyrenes and sulfur ylides. In most cases the reaction could be completed in CH3CN in the presence of Et3N at room temperature within 12 h, providing trans-2, 3-disubstitiuted dihydroindole derivetives in high to excellent yields. In particular, the products could be transformed to various indoline and indole compounds which are potentially biological and useful for pharmaceutical chemicals and other functional molecules. A plausible mechanism was proposed.
{"title":"Base-mediated diastereoselective synthesis of 2,3-disubstituted Indolines via [4 + 1] annulation","authors":"Xiaoxu Gao , Liting Xu , Peixin Shi, Jiawei Chen, Zhaohai Qin, Bin Fu","doi":"10.1016/j.tetlet.2025.155846","DOIUrl":"10.1016/j.tetlet.2025.155846","url":null,"abstract":"<div><div>An efficient approach to dihydroindole scaffold was developed via [4 + 1] annulation from 2-amino-<em>β</em>-nitrostyrenes and sulfur ylides. In most cases the reaction could be completed in CH<sub>3</sub>CN in the presence of Et<sub>3</sub>N at room temperature within 12 h, providing <em>trans-</em>2, 3-disubstitiuted dihydroindole derivetives in high to excellent yields. In particular, the products could be transformed to various indoline and indole compounds which are potentially biological and useful for pharmaceutical chemicals and other functional molecules. A plausible mechanism was proposed.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155846"},"PeriodicalIF":1.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264129","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 : 2025-10-02DOI: 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":"2025-10-02","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 : 2025-09-25DOI: 10.1016/j.tetlet.2025.155842
Zhiqi Lei , Xiaoyu Wang , Siqi Li , Xia Zhao , Kui Lu
We have developed a straightforward method for synthesizing distal difluoromethyl-substituted ketones bearing heteroaryl groups. This approach utilizes difluoromethylheteroarylation of unactivated alkenes through remote heteroaryl migration by employing bis(difluoroacetyl) peroxide (generated in situ from DFAA and urea·H₂O₂) as the difluoromethylating agent. Sunlight was proved to promote this transformation.
{"title":"Difluoromethylheteroarylation of unactivated alkenes through remote heteroaryl migration with bis(difluoroacetyl) peroxide","authors":"Zhiqi Lei , Xiaoyu Wang , Siqi Li , Xia Zhao , Kui Lu","doi":"10.1016/j.tetlet.2025.155842","DOIUrl":"10.1016/j.tetlet.2025.155842","url":null,"abstract":"<div><div>We have developed a straightforward method for synthesizing distal difluoromethyl-substituted ketones bearing heteroaryl groups. This approach utilizes difluoromethylheteroarylation of unactivated alkenes through remote heteroaryl migration by employing bis(difluoroacetyl) peroxide (generated in situ from DFAA and urea·H₂O₂) as the difluoromethylating agent. Sunlight was proved to promote this transformation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155842"},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218395","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 : 2025-09-25DOI: 10.1016/j.tetlet.2025.155843
Haneul Kang, Yeri Yoon, Sung-Gon Kim
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Nitroalkenes are well-established as versatile electrophilic partners in asymmetric annulation and cycloaddition reactions, enabling efficient access to structurally diverse, stereochemically rich heterocycles. Among their derivatives, (E)-2-nitroallylic carbonates–particularly (E)-2-nitroallylic acetates–have recently emerged as valuable bielectrophilic building blocks for cascade annulation processes. These substrates retain the key reactivity of nitroalkenes while exhibiting distinct behavior in Michael/Michael-type sequences due to their dual electrophilic nature. Unlike conventional nitroalkenes, (E)-2-nitroallylic acetates readily facilitate ring-forming transformations and have been effectively employed in both asymmetric and racemic catalytic systems. Notably, their use has enabled the construction of complex polycyclic architectures, including spirocycles and fused heterocycles, via efficient one-pot protocols. This review highlights recent advances in the chemistry of (E)-2-nitroallylic acetates, focusing on their role in enantioselective cascade reactions enabled by organocatalysts, as well as their application in racemic transformations.
{"title":"Recent advances in the annulation of (E)-2-nitroallylic acetates as bielectrophilic synthons","authors":"Haneul Kang, Yeri Yoon, Sung-Gon Kim","doi":"10.1016/j.tetlet.2025.155843","DOIUrl":"10.1016/j.tetlet.2025.155843","url":null,"abstract":"<div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (101KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div><div>Nitroalkenes are well-established as versatile electrophilic partners in asymmetric annulation and cycloaddition reactions, enabling efficient access to structurally diverse, stereochemically rich heterocycles. Among their derivatives, (<em>E</em>)-2-nitroallylic carbonates–particularly (<em>E</em>)-2-nitroallylic acetates–have recently emerged as valuable bielectrophilic building blocks for cascade annulation processes. These substrates retain the key reactivity of nitroalkenes while exhibiting distinct behavior in Michael/Michael-type sequences due to their dual electrophilic nature. Unlike conventional nitroalkenes, (<em>E</em>)-2-nitroallylic acetates readily facilitate ring-forming transformations and have been effectively employed in both asymmetric and racemic catalytic systems. Notably, their use has enabled the construction of complex polycyclic architectures, including spirocycles and fused heterocycles, via efficient one-pot protocols. This review highlights recent advances in the chemistry of (<em>E</em>)-2-nitroallylic acetates, focusing on their role in enantioselective cascade reactions enabled by organocatalysts, as well as their application in racemic transformations.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"173 ","pages":"Article 155843"},"PeriodicalIF":1.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145321786","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 : 2025-09-24DOI: 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":"2025-09-24","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}
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