Feng Z, Lubell W D
Département de Chimie, Université de Montréal, C. P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.
J Org Chem. 2001 Feb 23;66(4):1181-5. doi: 10.1021/jo001252l.
Enantiopure N-(BOC)amino-7-[3-azidopropyl]indolizidin-2-one acid 1 has been synthesized by displacement of the methanesulfonate of its 7-hydroxypropyl counterpart 11 with sodium azide and subsequent ester hydrolysis. N-(BOC)Amino-7-[3-hydroxypropyl]indolizidin-2-one ester 11 was obtained from a sequence commencing with the alkylation of (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(PhF)amino]azelate 5 (PhF = 9-(9-phenylfluorenyl)). Stereoselective allylation of 5, regioselective olefin hydroboration, selective primary alcohol protection as a silyl ether, and oxidation of the secondary alcohol gave (2S,4R,8S)-di-tert-butyl 4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into the indolizidinone heterocycle by a route featuring reductive amination, lactam cyclization, and isolation by way of a silyl ether which provided the (6S,7R)-isomer of 11.
对映体纯的N-(BOC)氨基-7-[3-叠氮基丙基]中氮茚-2-酮酸1是通过用叠氮化钠取代其7-羟丙基类似物11的甲磺酸酯并随后进行酯水解而合成的。N-(BOC)氨基-7-[3-羟丙基]中氮茚-2-酮酯11是从以(2S,8S)-二叔丁基5-氧代-2,8-二-[N-(PhF)氨基]壬二酸酯5（PhF = 9-(9-苯基芴基)）的烷基化开始的一系列反应中获得的。5的立体选择性烯丙基化、区域选择性烯烃硼氢化、作为硅醚的选择性伯醇保护以及仲醇的氧化得到(2S,4R,8S)-二叔丁基4-[3-叔丁基二甲基硅氧基丙基]-5-氧代-2,8-二-[N-(PhF)氨基]壬二酸酯9，其为纯非对映异构体，总收率为33%。然后通过以还原胺化、内酰胺环化以及通过提供11的(6S,7R)-异构体的硅醚进行分离为特征的路线将直链酮9转化为中氮茚酮杂环。
