N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Ave., 119991 Moscow, Russian Federation.
Org Biomol Chem. 2022 Jun 8;20(22):4569-4588. doi: 10.1039/d2ob00644h.
A general and stereoselective five-step approach to 14-membered cyclic bis-semicarbazones, 5,12-diaryl-7,14-dimethyl-1,2,4,8,9,11-hexaazacyclotetradeca-7,14-diene-3,10-diones, starting from aldehyde semicarbazones has been developed. The key intermediates, 4-(3-oxobut-1-yl)semicarbazones, were prepared by BF-catalyzed amidoalkylation of 2-(trimethylsilyloxy)propene with 4-[(aryl)(methoxy)methyl]- or 4-[(aryl)(tosyl)methyl]semicarbazones. Treatment of these intermediates with excess of hydrazine gave hydrazones of 4-(3-oxobut-1-yl)semicarbazones or 4-(3-oxobut-1-yl)semicarbazides, which in the presence of TsOH were converted into the target macrocycles. All steps of this approach could be scaled up easily to the multi-gram level.
我们开发了一种从醛缩氨基脲出发，经五步反应，以立体选择性方式合成 14 元环双缩氨基脲，5,12-二芳基-7,14-二甲基-1,2,4,8,9,11-六氮杂环十四烷-7,14-二烯-3,10-二酮的通用方法。关键中间体 4-(3-氧代丁基)缩氨基脲，由 BF3-催化的 2-(三甲基甲硅氧基)丙烯与 4-[(芳基)(甲氧基)甲基]-或 4-[(芳基)(甲苯磺酰基)甲基]缩氨基脲的酰胺烷基化反应制备。这些中间体与过量的肼反应，得到 4-(3-氧代丁基)缩氨基脲或 4-(3-氧代丁基)缩氨基脲的腙，在 TsOH 的存在下，将其转化为目标大环化合物。该方法的所有步骤都可以很容易地放大到多克级规模。
