Deciphering substitution effects on reductive hydroalkoxylation of alkynyl aminols for stereoselective synthesis of morpholines and 1,4-oxazepanes: total synthesis of tridemorph and fenpropimorph†‡
Santosh J. Gharpure, Deepika Kalita, Shipra Somani and Juhi Pal
{"title":"Deciphering substitution effects on reductive hydroalkoxylation of alkynyl aminols for stereoselective synthesis of morpholines and 1,4-oxazepanes: total synthesis of tridemorph and fenpropimorph†‡","authors":"Santosh J. Gharpure, Deepika Kalita, Shipra Somani and Juhi Pal","doi":"10.1039/D4OB00855C","DOIUrl":null,"url":null,"abstract":"<p >Acid catalysed reductive etherification of <em>N</em>-propargyl amino alcohols for the stereoselective synthesis of <em>cis</em>-2,5/2,6-disubstituted morpholines and <em>cis</em>-2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines <em>via</em> a 6-<em>exo-dig</em> hydroalkoxylation–isomerization–reduction cascade. Interestingly, an alkyne hydration–cyclization–reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols. The strategy was used as a key step in the total synthesis of fungicides tridemorph and fenpropimorph.</p>","PeriodicalId":96,"journal":{"name":"Organic & Biomolecular Chemistry","volume":null,"pages":null},"PeriodicalIF":2.9000,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic & Biomolecular Chemistry","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/ob/d4ob00855c","RegionNum":3,"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
Abstract
Acid catalysed reductive etherification of N-propargyl amino alcohols for the stereoselective synthesis of cis-2,5/2,6-disubstituted morpholines and cis-2,6/2,7-disubstituted oxazepanes has been developed. Mechanistic studies revealed that terminal alkynols gave morpholines via a 6-exo-dig hydroalkoxylation–isomerization–reduction cascade. Interestingly, an alkyne hydration–cyclization–reduction sequence is found to be involved in the formation of oxazepanes from alkyl substituted internal alkynols. The strategy was used as a key step in the total synthesis of fungicides tridemorph and fenpropimorph.