A short synthetic route to (+)-austamide, (+)-deoxyisoaustamide, and (+)-hydratoaustamide from a common precursor by a novel palladium-mediated indole→dihydroindoloazocine cyclization
A short synthetic route to (+)-austamide, (+)-deoxyisoaustamide, and (+)-hydratoaustamide from a common precursor by a novel palladium-mediated indole→dihydroindoloazocine cyclization
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DOI：
10.1021/ja026663t
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发表时间：
2002-07-10
影响因子：
15
通讯作者：
Corey, EJ
中科院分区：
文献类型：
--
作者：
Baran, PS;Corey, EJ
描述了首次通过非常直接的路线合成(+)-奥司他胺(1)、(+)-脱氧异辛基亚胺(2)和(+)-氢代亚胺(10)(方案1)。以色氨酸甲酯(3)为起始原料，经两步反应制得中间体5，总收率98%。合成的关键步骤是涉及有机钯中间体的5的新型环化反应，该反应得到二氢偶氮6。从这个关键中间体只需几个步骤就可以获得目标结构，如方案1所示。5→6的显著转化可以通过方案2所示的机制途径来合理化，该途径涉及包括苍白、环化和重排在内的多步骤序列。
The first synthesis of (+)-austamide (1), (+)-deoxyisoaustamide (2), and (+)-hydratoaustamide (10) by a very direct route is described (Scheme 1). Starting from tryptophan methyl ester (3) intermediate5is generated in two steps in >98% overall yield. The key step in the synthesis is a novel cyclization of5involving organopalladium intermediates which gives the dihydroazocine6. From this key intermediate the target structures are accessible in just a few steps as shown in Scheme 1. The remarkable conversion of5→6can be rationalized by the mechanistic pathway shown in Scheme 2 that involves a multistep sequence which includes palladation, cyclization, and rearrangement.