{"title":"钴催化与碱促进的骨架和立体发散合成双环α-C-、β-O-和α- o -糖苷","authors":"Zhen Cao, Yujie Niu, Xingxing Jiang, Linxuan Li, Nengzhong Wang*, Nianyu Huang* and Hui Yao*, ","doi":"10.1021/acs.orglett.5c0143310.1021/acs.orglett.5c01433","DOIUrl":null,"url":null,"abstract":"<p >A stereodivergent synthesis of bicyclic α-<i>C</i>-, β-<i>O</i>-, and α-<i>O</i>-glycosides is achieved with nonprecious Co(dpm)<sub>3</sub>, K<sub>2</sub>CO<sub>3</sub>, and DBU, respectively. Cobalt-catalyzed decarboxylative allylation of 2,3-unsaturated 4-keto glycosyl carbonates with 1,3-diketones delivers α-<i>C</i>-glycosides in good yields with exclusive chemo- and regiocontrol and excellent diastereoselectivity (>20:1 dr). K<sub>2</sub>CO<sub>3</sub> enables β-<i>O</i>-glycosides via a cascaded intermolecular Michael addition/S<sub>N</sub>2-like cyclization, whereas DBU promotes further C5 epimerization to give α-<i>O</i>-glycosides. Mechanistic studies (deuterium labeling and intermediate capturing) validate the pathways. Gram-scale synthesis and late-stage functionalization of pharmaceuticals demonstrate practicality.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"27 20","pages":"5230–5235 5230–5235"},"PeriodicalIF":5.0000,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cobalt-Catalyzed versus Base-Promoted Skeletal- and Stereodivergent Synthesis of Bicyclic α-C-, β-O-, and α-O-Glycosides\",\"authors\":\"Zhen Cao, Yujie Niu, Xingxing Jiang, Linxuan Li, Nengzhong Wang*, Nianyu Huang* and Hui Yao*, \",\"doi\":\"10.1021/acs.orglett.5c0143310.1021/acs.orglett.5c01433\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >A stereodivergent synthesis of bicyclic α-<i>C</i>-, β-<i>O</i>-, and α-<i>O</i>-glycosides is achieved with nonprecious Co(dpm)<sub>3</sub>, K<sub>2</sub>CO<sub>3</sub>, and DBU, respectively. Cobalt-catalyzed decarboxylative allylation of 2,3-unsaturated 4-keto glycosyl carbonates with 1,3-diketones delivers α-<i>C</i>-glycosides in good yields with exclusive chemo- and regiocontrol and excellent diastereoselectivity (>20:1 dr). K<sub>2</sub>CO<sub>3</sub> enables β-<i>O</i>-glycosides via a cascaded intermolecular Michael addition/S<sub>N</sub>2-like cyclization, whereas DBU promotes further C5 epimerization to give α-<i>O</i>-glycosides. Mechanistic studies (deuterium labeling and intermediate capturing) validate the pathways. Gram-scale synthesis and late-stage functionalization of pharmaceuticals demonstrate practicality.</p>\",\"PeriodicalId\":54,\"journal\":{\"name\":\"Organic Letters\",\"volume\":\"27 20\",\"pages\":\"5230–5235 5230–5235\"},\"PeriodicalIF\":5.0000,\"publicationDate\":\"2025-05-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Organic Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acs.orglett.5c01433\",\"RegionNum\":1,\"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":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acs.orglett.5c01433","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
摘要
用非贵金属Co(dpm)3、K2CO3和DBU分别合成了双环α-C-、β-O-和α- o -糖苷。钴催化的2,3-不饱和4-酮碳酸糖基与1,3-二酮的脱羧烯丙基化反应具有独特的化学和区域控制以及优异的非对映选择性,产率高(20:1 dr)。K2CO3通过级联的分子间Michael加成反应/ sn2样环化反应生成β- o -糖苷,而DBU则进一步促进C5外映反应生成α- o -糖苷。机制研究(氘标记和中间体捕获)验证了这些途径。克级合成和后期药物功能化证明了实用性。
Cobalt-Catalyzed versus Base-Promoted Skeletal- and Stereodivergent Synthesis of Bicyclic α-C-, β-O-, and α-O-Glycosides
A stereodivergent synthesis of bicyclic α-C-, β-O-, and α-O-glycosides is achieved with nonprecious Co(dpm)3, K2CO3, and DBU, respectively. Cobalt-catalyzed decarboxylative allylation of 2,3-unsaturated 4-keto glycosyl carbonates with 1,3-diketones delivers α-C-glycosides in good yields with exclusive chemo- and regiocontrol and excellent diastereoselectivity (>20:1 dr). K2CO3 enables β-O-glycosides via a cascaded intermolecular Michael addition/SN2-like cyclization, whereas DBU promotes further C5 epimerization to give α-O-glycosides. Mechanistic studies (deuterium labeling and intermediate capturing) validate the pathways. Gram-scale synthesis and late-stage functionalization of pharmaceuticals demonstrate practicality.
期刊介绍:
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.