{"title":"光学纯反式-2-(3,5-二甲基苯氧基)环己-1-醇作为制备α-取代羧酸衍生物的手性助剂的合成与应用","authors":"","doi":"10.1016/j.tet.2024.134326","DOIUrl":null,"url":null,"abstract":"<div><div>In the present work, <em>trans</em>-2-(3,5-dimethylphenoxy)cyclohexan-1-ol was synthesized and its enantiomers were separated by Enzymatic Kinetic Resolution (EKR). The absolute configuration was established by converting to diastereomer with esters of known chiral description. Chiral alcohol was then used as an auxiliary for the preparation of esters by coupling with racemic α-halo acids in presence of DCC and a suitable base. We observed an efficient Dynamic Kinetic Resolution as the product esters were obtained in enriched diastereomeric forms. Effect of several parameters like base, temperature and reaction time was studied. The relative energy profile of the diastereomers was studied by computational analysis and the energy difference of diastereomeric products were in accordance with the observed diastereoselectivity. The chirally pure α-halo acid could be separated from the auxiliary, without any loss of optical purity of both components.</div></div>","PeriodicalId":437,"journal":{"name":"Tetrahedron","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and applications of optically pure trans-2-(3,5-dimethylphenoxy)cyclohexan-1-ol as chiral auxiliary for preparation of α-substituted carboxylic acid derivatives\",\"authors\":\"\",\"doi\":\"10.1016/j.tet.2024.134326\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>In the present work, <em>trans</em>-2-(3,5-dimethylphenoxy)cyclohexan-1-ol was synthesized and its enantiomers were separated by Enzymatic Kinetic Resolution (EKR). The absolute configuration was established by converting to diastereomer with esters of known chiral description. Chiral alcohol was then used as an auxiliary for the preparation of esters by coupling with racemic α-halo acids in presence of DCC and a suitable base. We observed an efficient Dynamic Kinetic Resolution as the product esters were obtained in enriched diastereomeric forms. Effect of several parameters like base, temperature and reaction time was studied. The relative energy profile of the diastereomers was studied by computational analysis and the energy difference of diastereomeric products were in accordance with the observed diastereoselectivity. The chirally pure α-halo acid could be separated from the auxiliary, without any loss of optical purity of both components.</div></div>\",\"PeriodicalId\":437,\"journal\":{\"name\":\"Tetrahedron\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tetrahedron\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0040402024005076\",\"RegionNum\":3,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tetrahedron","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040402024005076","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Synthesis and applications of optically pure trans-2-(3,5-dimethylphenoxy)cyclohexan-1-ol as chiral auxiliary for preparation of α-substituted carboxylic acid derivatives
In the present work, trans-2-(3,5-dimethylphenoxy)cyclohexan-1-ol was synthesized and its enantiomers were separated by Enzymatic Kinetic Resolution (EKR). The absolute configuration was established by converting to diastereomer with esters of known chiral description. Chiral alcohol was then used as an auxiliary for the preparation of esters by coupling with racemic α-halo acids in presence of DCC and a suitable base. We observed an efficient Dynamic Kinetic Resolution as the product esters were obtained in enriched diastereomeric forms. Effect of several parameters like base, temperature and reaction time was studied. The relative energy profile of the diastereomers was studied by computational analysis and the energy difference of diastereomeric products were in accordance with the observed diastereoselectivity. The chirally pure α-halo acid could be separated from the auxiliary, without any loss of optical purity of both components.
期刊介绍:
Tetrahedron publishes full accounts of research having outstanding significance in the broad field of organic chemistry and its related disciplines, such as organic materials and bio-organic chemistry.
Regular papers in Tetrahedron are expected to represent detailed accounts of an original study having substantially greater scope and details than that found in a communication, as published in Tetrahedron Letters.
Tetrahedron also publishes thematic collections of papers as special issues and ''Reports'', commissioned in-depth reviews providing a comprehensive overview of a research area.