Marylise Triacca, Carl D. Reens, Hamish Stephen and Kevin Lam
{"title":"埃斯皮罗:一种可扩展和可持续的电合成途径,通过丙二酸的阳极氧化产生螺旋酮","authors":"Marylise Triacca, Carl D. Reens, Hamish Stephen and Kevin Lam","doi":"10.1039/D5GC01767J","DOIUrl":null,"url":null,"abstract":"<p >Spiroketals are important structural motifs found in natural products, pharmaceuticals, and agrochemicals. However, their synthesis often requires hazardous reagents and harsh conditions, limiting their accessibility. Here, we present eSpiro, a novel electrosynthetic method for the efficient and sustainable synthesis of spiroketals <em>via</em> anodic oxidation of malonic acids. This approach offers a metal- and mercury-free alternative to conventional acid-catalysed or transition metal-mediated cyclisations. The reaction proceeds through a sequential Hofer-Moest decarboxylation, followed by Brønsted acid-mediated cyclisation, achieving high yields with broad functional group tolerance. We further explore the reaction scope and demonstrate its scalability, achieving up to 98% yield in batch. Additionally, we investigate a flow electrolysis setup, highlighting key challenges such as substrate stability, in-line solvent system switch and gas evolution, and also demonstrating preliminary success in integrating electrochemical oxidation with downstream acid-catalysed cyclisation. This work provides a practical and eco-friendly route to spiroketals, with potential for industrial applications in organic synthesis.</p>","PeriodicalId":78,"journal":{"name":"Green Chemistry","volume":" 25","pages":" 7513-7517"},"PeriodicalIF":9.3000,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"eSpiro: A scalable and sustainable electrosynthetic route to spiroketals via anodic oxidation of malonic acids†\",\"authors\":\"Marylise Triacca, Carl D. Reens, Hamish Stephen and Kevin Lam\",\"doi\":\"10.1039/D5GC01767J\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Spiroketals are important structural motifs found in natural products, pharmaceuticals, and agrochemicals. However, their synthesis often requires hazardous reagents and harsh conditions, limiting their accessibility. Here, we present eSpiro, a novel electrosynthetic method for the efficient and sustainable synthesis of spiroketals <em>via</em> anodic oxidation of malonic acids. This approach offers a metal- and mercury-free alternative to conventional acid-catalysed or transition metal-mediated cyclisations. The reaction proceeds through a sequential Hofer-Moest decarboxylation, followed by Brønsted acid-mediated cyclisation, achieving high yields with broad functional group tolerance. We further explore the reaction scope and demonstrate its scalability, achieving up to 98% yield in batch. Additionally, we investigate a flow electrolysis setup, highlighting key challenges such as substrate stability, in-line solvent system switch and gas evolution, and also demonstrating preliminary success in integrating electrochemical oxidation with downstream acid-catalysed cyclisation. This work provides a practical and eco-friendly route to spiroketals, with potential for industrial applications in organic synthesis.</p>\",\"PeriodicalId\":78,\"journal\":{\"name\":\"Green Chemistry\",\"volume\":\" 25\",\"pages\":\" 7513-7517\"},\"PeriodicalIF\":9.3000,\"publicationDate\":\"2025-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Green Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.rsc.org/en/content/articlelanding/2025/gc/d5gc01767j\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Green Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2025/gc/d5gc01767j","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
eSpiro: A scalable and sustainable electrosynthetic route to spiroketals via anodic oxidation of malonic acids†
Spiroketals are important structural motifs found in natural products, pharmaceuticals, and agrochemicals. However, their synthesis often requires hazardous reagents and harsh conditions, limiting their accessibility. Here, we present eSpiro, a novel electrosynthetic method for the efficient and sustainable synthesis of spiroketals via anodic oxidation of malonic acids. This approach offers a metal- and mercury-free alternative to conventional acid-catalysed or transition metal-mediated cyclisations. The reaction proceeds through a sequential Hofer-Moest decarboxylation, followed by Brønsted acid-mediated cyclisation, achieving high yields with broad functional group tolerance. We further explore the reaction scope and demonstrate its scalability, achieving up to 98% yield in batch. Additionally, we investigate a flow electrolysis setup, highlighting key challenges such as substrate stability, in-line solvent system switch and gas evolution, and also demonstrating preliminary success in integrating electrochemical oxidation with downstream acid-catalysed cyclisation. This work provides a practical and eco-friendly route to spiroketals, with potential for industrial applications in organic synthesis.
期刊介绍:
Green Chemistry is a journal that provides a unique forum for the publication of innovative research on the development of alternative green and sustainable technologies. The scope of Green Chemistry is based on the definition proposed by Anastas and Warner (Green Chemistry: Theory and Practice, P T Anastas and J C Warner, Oxford University Press, Oxford, 1998), which defines green chemistry as the utilisation of a set of principles that reduces or eliminates the use or generation of hazardous substances in the design, manufacture and application of chemical products. Green Chemistry aims to reduce the environmental impact of the chemical enterprise by developing a technology base that is inherently non-toxic to living things and the environment. The journal welcomes submissions on all aspects of research relating to this endeavor and publishes original and significant cutting-edge research that is likely to be of wide general appeal. For a work to be published, it must present a significant advance in green chemistry, including a comparison with existing methods and a demonstration of advantages over those methods.