A practical and efficient synthesis of 6-carboalkoxy-13-cycloalkyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid derivatives

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• 作者：Piyasena Hewawasam ; Yong Tu ; Thomas W. Hudyma ; Xiaofan Zhang ; Robert G. Gentles ; John F. Kadow ; Nicholas A. Meanwell
• 关键词：Michael addition ; Horner&ndash ; Wadsworth&ndash ; Emmons reaction ; Indolo[2 ; 1-a][2]benzazepine ; Ring closing metathesis
• 刊名：Tetrahedron Letters
• 出版年：5 February, 2014
• 年：2014
• 卷：55
• 期：6
• 页码：1148-1153
• 全文大小：2116 K

文摘

A convenient and practical synthesis of 6-carboalkoxy-13-cycloalkyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid derivatives (6) has been developed. The key step in the synthesis utilizes an intramolecular tandem reaction sequence of a Michael addition followed by a Horner-Wadsworth-Emmons (HWE) olefination reaction between hemi-aminal 11 and methyl 2-(dimethoxyphosphoryl)acrylate 12. The ring construction occurred efficiently and purification of the products 6 was straightforward. The C-10 methyl ester of 6a was hydrolyzed selectively to the carboxylic acid 13 while the olefin of 6d was converted to the cyclopropane 14 using trimethylsulfoxonium iodide in DMSO in the presence of NaH.