Hurley Paul B, Dake Gregory R
Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, B.C., Canada.
J Org Chem. 2008 Jun 6;73(11):4131-8. doi: 10.1021/jo800336k. Epub 2008 Apr 30.
The investigations of a synthetic route incorporating a NBS-promoted semipinacol rearrangement to the 6-azaspiro[4.5]decane fragment within halichlorine ( 1) are presented. A convergent approach was pursued, utilizing two chiral, enantiomerically enriched building blocks, 2-trimethylstannyl piperidene 10 and substituted cyclobutanone 19. Noteworthy synthetic operations in this study include the following: (a) a highly diastereoselective NBS-promoted semipinacol reaction that established four stereogenic centers in ketone 25 and (b) the use of a N- p-toluenesulfonyl-2-iodo-2-piperidene as a precursor to a basic organometallic reagent, which was critical to the success of the coupling of fragments 10 and 19.
本文介绍了在卤氯灵（1）中引入NBS促进的半频哪醇重排以构建6-氮杂螺[4.5]癸烷片段的合成路线研究。采用了一种汇聚式方法，使用了两个手性、对映体富集的构建单元，即2-三甲基锡基哌啶10和取代环丁酮19。本研究中值得注意的合成操作包括：（a）在酮25中建立四个立体中心的高度非对映选择性NBS促进的半频哪醇反应；（b）使用N-对甲苯磺酰基-2-碘-2-哌啶作为碱性有机金属试剂的前体，这对片段10和19的偶联成功至关重要。
