{"title":"通过分子间Rh(I)催化的[2 + 2 + 2]环三聚反应,不对称合成异构体β-咔啉","authors":"","doi":"10.1016/j.tetlet.2024.155187","DOIUrl":null,"url":null,"abstract":"<div><p>The rational design of atropisomeric small molecules is becoming increasingly common in chemical synthesis as a result of the unique advantages this property provides in drug discovery, asymmetric catalysis, and chiroptical activity. In this study, we designed a synthesis of a configurationally stable β-carboline in six steps. Our synthesis made use of an innovative Grignard addition/elimination reaction that formed an yne-ynamide precursor that then reacted with ethyl cyanoformate in a rhodium(I)-catalyzed [2 + 2 + 2] cyclotrimerization reaction to give the atropisomeric β-carboline in excellent yield, good enantioselectivity, and excellent regioselectivity. Extensive optimization of this transformation is described. Racemization kinetics experiments were also conducted on the individual atropisomers and their absolute configurations were determined by circular dichroism.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Asymmetric synthesis of an atropisomeric β-carboline via regioselective intermolecular Rh(I)-catalyzed [2 + 2 + 2] cyclotrimerization\",\"authors\":\"\",\"doi\":\"10.1016/j.tetlet.2024.155187\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The rational design of atropisomeric small molecules is becoming increasingly common in chemical synthesis as a result of the unique advantages this property provides in drug discovery, asymmetric catalysis, and chiroptical activity. In this study, we designed a synthesis of a configurationally stable β-carboline in six steps. Our synthesis made use of an innovative Grignard addition/elimination reaction that formed an yne-ynamide precursor that then reacted with ethyl cyanoformate in a rhodium(I)-catalyzed [2 + 2 + 2] cyclotrimerization reaction to give the atropisomeric β-carboline in excellent yield, good enantioselectivity, and excellent regioselectivity. Extensive optimization of this transformation is described. Racemization kinetics experiments were also conducted on the individual atropisomers and their absolute configurations were determined by circular dichroism.</p></div>\",\"PeriodicalId\":438,\"journal\":{\"name\":\"Tetrahedron Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tetrahedron Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S004040392400282X\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tetrahedron Letters","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S004040392400282X","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Asymmetric synthesis of an atropisomeric β-carboline via regioselective intermolecular Rh(I)-catalyzed [2 + 2 + 2] cyclotrimerization
The rational design of atropisomeric small molecules is becoming increasingly common in chemical synthesis as a result of the unique advantages this property provides in drug discovery, asymmetric catalysis, and chiroptical activity. In this study, we designed a synthesis of a configurationally stable β-carboline in six steps. Our synthesis made use of an innovative Grignard addition/elimination reaction that formed an yne-ynamide precursor that then reacted with ethyl cyanoformate in a rhodium(I)-catalyzed [2 + 2 + 2] cyclotrimerization reaction to give the atropisomeric β-carboline in excellent yield, good enantioselectivity, and excellent regioselectivity. Extensive optimization of this transformation is described. Racemization kinetics experiments were also conducted on the individual atropisomers and their absolute configurations were determined by circular dichroism.
期刊介绍:
Tetrahedron Letters provides maximum dissemination of outstanding developments in organic chemistry. The journal is published weekly and covers developments in techniques, structures, methods and conclusions in experimental and theoretical organic chemistry. Rapid publication of timely and significant research results enables researchers from all over the world to transmit quickly their new contributions to large, international audiences.