Marianna Danopoulou, Leandros P. Zorba, Athanasia P. Karantoni, Demeter Tzeli, Georgios C. Vougioukalakis
{"title":"铜催化的芳基乙腈与苄醇的α-烷基化反应","authors":"Marianna Danopoulou, Leandros P. Zorba, Athanasia P. Karantoni, Demeter Tzeli, Georgios C. Vougioukalakis","doi":"10.1021/acs.joc.4c01662","DOIUrl":null,"url":null,"abstract":"A highly efficient, <i>in situ</i> formed CuCl<sub>2</sub>/TMEDA catalytic system (TMEDA = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads to the synthesis of α-alkylated nitriles in up to 99% yield. Experimental mechanistic investigations reveal that the key step of this transformation is the C(sp<sup>3</sup>)–H functionalization of the alcohol, taking place <i>via</i> a hydrogen atom abstraction, with the simultaneous formation of copper-hydride species. Detailed density functional theory studies shed light on all reaction steps, confirming the catalytic pathway proposed on the basis of the experimental findings.","PeriodicalId":57,"journal":{"name":"The Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Copper-Catalyzed α-Alkylation of Aryl Acetonitriles with Benzyl Alcohols\",\"authors\":\"Marianna Danopoulou, Leandros P. Zorba, Athanasia P. Karantoni, Demeter Tzeli, Georgios C. Vougioukalakis\",\"doi\":\"10.1021/acs.joc.4c01662\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"A highly efficient, <i>in situ</i> formed CuCl<sub>2</sub>/TMEDA catalytic system (TMEDA = <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads to the synthesis of α-alkylated nitriles in up to 99% yield. Experimental mechanistic investigations reveal that the key step of this transformation is the C(sp<sup>3</sup>)–H functionalization of the alcohol, taking place <i>via</i> a hydrogen atom abstraction, with the simultaneous formation of copper-hydride species. Detailed density functional theory studies shed light on all reaction steps, confirming the catalytic pathway proposed on the basis of the experimental findings.\",\"PeriodicalId\":57,\"journal\":{\"name\":\"The Journal of Organic Chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.3000,\"publicationDate\":\"2024-09-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The Journal of Organic Chemistry\",\"FirstCategoryId\":\"1\",\"ListUrlMain\":\"https://doi.org/10.1021/acs.joc.4c01662\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The Journal of Organic Chemistry","FirstCategoryId":"1","ListUrlMain":"https://doi.org/10.1021/acs.joc.4c01662","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Copper-Catalyzed α-Alkylation of Aryl Acetonitriles with Benzyl Alcohols
A highly efficient, in situ formed CuCl2/TMEDA catalytic system (TMEDA = N,N,N′,N′-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads to the synthesis of α-alkylated nitriles in up to 99% yield. Experimental mechanistic investigations reveal that the key step of this transformation is the C(sp3)–H functionalization of the alcohol, taking place via a hydrogen atom abstraction, with the simultaneous formation of copper-hydride species. Detailed density functional theory studies shed light on all reaction steps, confirming the catalytic pathway proposed on the basis of the experimental findings.
期刊介绍:
The Journal of Organic Chemistry welcomes original contributions of fundamental research in all branches of the theory and practice of organic chemistry. In selecting manuscripts for publication, the editors place emphasis on the quality and novelty of the work, as well as the breadth of interest to the organic chemistry community.