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Addition of HO-acids to N,N-Bis(oxy)enamines: Mechanism, Scope and Application to the Synthesis of Pharmaceuticalsстатья
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 3 декабря 2017 г.
- Авторы: Sukhorukov Alexey Yu, Naumovich Yana A., Ivan Golovanov, Ioffe Sema L.
- Журнал: European Journal of Organic Chemistry
- Номер: 41
- Год издания: 2017
- Издательство: John Wiley & Sons Ltd.
- Местоположение издательства: United Kingdom
- Первая страница: 6209
- Последняя страница: 6227
- DOI: 10.1002/ejoc.201701266
- Аннотация: The regioselectivity of the addition of HO-acids to the activated pi-bond in N,N-bis(oxy)enamines was found to be dramatically dependent on the solvent. Mechanism investigations and quantum-chemical calculations revealed that solvent affects the reaction pathway. In basic solvents (DMF, NMP, DMSO), N,N-bis(oxy)enamines are converted into nitrosoalkenes through a Lewis base promoted process followed by the oxy-Michael addition of HO-acid. In non-polar solvents (toluene, CH2Cl2), reaction follows an acid-promoted SN' substitution of N-oxy-group via highly reactive N-vinyl-N-alkoxynitrenium species. Based on these studies, general and efficient protocols for oximinoalkylation of various HO-acids (carboxylic acids, phenols, hydroxamic, phosphoric and sulfonic acids) employing readily available N,N-bis(oxy)enamines were developed. These methods proved to be applicable for post-modification of natural molecules bearing acidic OH-groups (such as steroidal hormones, bile acids, protected amino acids and peptides) and ligands (BINOL). The resulting alpha-oxyoximes were demonstrated to be useful precursors of valuable 1,2-amino alcohol or 1,2-hydroxylamino alcohol derivatives, including the antiarrhythmic drug Mexiletine and a potent MMP inhibitor.
- Добавил в систему: Сухоруков Алексей Юрьевич