Hao Wu, Yiyao Wang, Shiyuan Sui, Gongming Chen, Lei Wang, Jiaxin Yang, Junbiao Chang, Dachang Bai
{"title":"通过 C-C 活化实现环丙烷的对映选择性去对称化和平行动力学解析:手性 β-内酰胺的合成","authors":"Hao Wu, Yiyao Wang, Shiyuan Sui, Gongming Chen, Lei Wang, Jiaxin Yang, Junbiao Chang, Dachang Bai","doi":"10.1016/j.chempr.2024.08.005","DOIUrl":null,"url":null,"abstract":"<p>β-Lactams are privileged and appealing motifs in medicinal chemistry. Herein, we report enantioselective desymmetrization and parallel kinetic resolution of aminocyclopropanes for the synthesis of chiral β-lactams through Rh(I)-catalyzed asymmetric C–C bond activation. The chiral Rh(I) catalyzed C–C bond cleavage of aminocyclopropanes first and then underwent β-hydride elimination to generate π-allylic hydridorhodium(III) intermediates, which could be trapped by tethered alkyne units, and gave various strained chiral β-lactams with excellent <em>regio</em>- and enantioselectivity (90%–99% ee). Moreover, parallel kinetic resolution was realized when using unsymmetrical aminocyclopropanes with pre-existing C2-stereocenters through C–C bond activation, delivering two types of β-lactams in one pot with excellent enantiomeric excesses. Notably, these systems achieve complete atom and step economy. The obtained enantioenriched β-lactams exhibit the capability to undergo a variety of stereospecific transformations. Theoretical calculations reveal the origin of enantioselectivity and support the alkyne unit insertion to allylic Rh(III) –C bond mechanisms.</p>","PeriodicalId":268,"journal":{"name":"Chem","volume":null,"pages":null},"PeriodicalIF":19.1000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Enantioselective desymmetrization and parallel kinetic resolution of cyclopropanes via C–C activation: Synthesis of chiral β-lactams\",\"authors\":\"Hao Wu, Yiyao Wang, Shiyuan Sui, Gongming Chen, Lei Wang, Jiaxin Yang, Junbiao Chang, Dachang Bai\",\"doi\":\"10.1016/j.chempr.2024.08.005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>β-Lactams are privileged and appealing motifs in medicinal chemistry. Herein, we report enantioselective desymmetrization and parallel kinetic resolution of aminocyclopropanes for the synthesis of chiral β-lactams through Rh(I)-catalyzed asymmetric C–C bond activation. The chiral Rh(I) catalyzed C–C bond cleavage of aminocyclopropanes first and then underwent β-hydride elimination to generate π-allylic hydridorhodium(III) intermediates, which could be trapped by tethered alkyne units, and gave various strained chiral β-lactams with excellent <em>regio</em>- and enantioselectivity (90%–99% ee). Moreover, parallel kinetic resolution was realized when using unsymmetrical aminocyclopropanes with pre-existing C2-stereocenters through C–C bond activation, delivering two types of β-lactams in one pot with excellent enantiomeric excesses. Notably, these systems achieve complete atom and step economy. The obtained enantioenriched β-lactams exhibit the capability to undergo a variety of stereospecific transformations. Theoretical calculations reveal the origin of enantioselectivity and support the alkyne unit insertion to allylic Rh(III) –C bond mechanisms.</p>\",\"PeriodicalId\":268,\"journal\":{\"name\":\"Chem\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":19.1000,\"publicationDate\":\"2024-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chem\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1016/j.chempr.2024.08.005\",\"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":"Chem","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1016/j.chempr.2024.08.005","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Enantioselective desymmetrization and parallel kinetic resolution of cyclopropanes via C–C activation: Synthesis of chiral β-lactams
β-Lactams are privileged and appealing motifs in medicinal chemistry. Herein, we report enantioselective desymmetrization and parallel kinetic resolution of aminocyclopropanes for the synthesis of chiral β-lactams through Rh(I)-catalyzed asymmetric C–C bond activation. The chiral Rh(I) catalyzed C–C bond cleavage of aminocyclopropanes first and then underwent β-hydride elimination to generate π-allylic hydridorhodium(III) intermediates, which could be trapped by tethered alkyne units, and gave various strained chiral β-lactams with excellent regio- and enantioselectivity (90%–99% ee). Moreover, parallel kinetic resolution was realized when using unsymmetrical aminocyclopropanes with pre-existing C2-stereocenters through C–C bond activation, delivering two types of β-lactams in one pot with excellent enantiomeric excesses. Notably, these systems achieve complete atom and step economy. The obtained enantioenriched β-lactams exhibit the capability to undergo a variety of stereospecific transformations. Theoretical calculations reveal the origin of enantioselectivity and support the alkyne unit insertion to allylic Rh(III) –C bond mechanisms.
期刊介绍:
Chem, affiliated with Cell as its sister journal, serves as a platform for groundbreaking research and illustrates how fundamental inquiries in chemistry and its related fields can contribute to addressing future global challenges. It was established in 2016, and is currently edited by Robert Eagling.