Run Lu, Jie Yang, Jia-Ming Jiang, Jie Wang, Wei Huang, Cheng Peng, Gu Zhan, Bo Han
{"title":"Catalyst-Controlled Divergent Synthesis of Bicyclo[2.1.1]hexanes and Cyclobutenes: The Unique Effect of Au(I).","authors":"Run Lu, Jie Yang, Jia-Ming Jiang, Jie Wang, Wei Huang, Cheng Peng, Gu Zhan, Bo Han","doi":"10.1021/jacsau.5c00341","DOIUrl":null,"url":null,"abstract":"<p><p>Catalyst-controlled chemodivergent synthesis is a powerful strategy for exploring the chemical space. We report a Cu-(I)/Au-(I)-catalyzed chemodivergent reaction of bicyclo[1.1.0]-butane amides with azadienes, enabling access to two valuable product classes: bicyclo[2.1.1]-hexanes and cyclobutenes. Cu-(I) catalysis promotes a highly efficient formal cycloaddition to furnish bicyclo[2.1.1]-hexanes, whereas Au-(I) uniquely facilitates an addition-elimination pathway, selectively yielding cyclobutenes. Both transformations exhibit excellent chemoselectivity, high efficiency, and a broad substrate scope. The multifunctionalized products are readily scalable to gram quantities and undergo diverse downstream modifications including spirocyclization. DFT calculations provide mechanistic insight into divergent reactivity. Cu-(I) favors a linear two-coordinate geometry in the transition state, accelerating the intramolecular cyclization. In contrast, Au-(I) stabilizes key intermediates via a four-coordinate geometry, enabling intramolecular proton transfer and reversing the inherent chemoselectivity. This work highlights Au-(I)'s unique property as a useful tool for controlling reaction pathways and expanding chemical space through molecular diversification.</p>","PeriodicalId":94060,"journal":{"name":"JACS Au","volume":"5 6","pages":"2738-2748"},"PeriodicalIF":8.5000,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188400/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JACS Au","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1021/jacsau.5c00341","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/23 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Catalyst-controlled chemodivergent synthesis is a powerful strategy for exploring the chemical space. We report a Cu-(I)/Au-(I)-catalyzed chemodivergent reaction of bicyclo[1.1.0]-butane amides with azadienes, enabling access to two valuable product classes: bicyclo[2.1.1]-hexanes and cyclobutenes. Cu-(I) catalysis promotes a highly efficient formal cycloaddition to furnish bicyclo[2.1.1]-hexanes, whereas Au-(I) uniquely facilitates an addition-elimination pathway, selectively yielding cyclobutenes. Both transformations exhibit excellent chemoselectivity, high efficiency, and a broad substrate scope. The multifunctionalized products are readily scalable to gram quantities and undergo diverse downstream modifications including spirocyclization. DFT calculations provide mechanistic insight into divergent reactivity. Cu-(I) favors a linear two-coordinate geometry in the transition state, accelerating the intramolecular cyclization. In contrast, Au-(I) stabilizes key intermediates via a four-coordinate geometry, enabling intramolecular proton transfer and reversing the inherent chemoselectivity. This work highlights Au-(I)'s unique property as a useful tool for controlling reaction pathways and expanding chemical space through molecular diversification.