Gotchev Dimitar B, Comins Daniel L
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
J Org Chem. 2006 Dec 8;71(25):9393-402. doi: 10.1021/jo061677t.
Two approaches to the aza-tricyclo dodecane skeleton of (-)-FR901483 are reported. Both routes utilized a Grignard addition to an N-acylpyridinium salt to establish the absolute stereochemistry at C-6 and a highly diastereoselective conjugate allylation reaction to form the quaternary center at C-1 of the natural product in an excellent yield. Although the desired polysubstituted piperidine intermediates were prepared regio- and stereoselectively, the construction of the C-8/C-9 bond connectivity could not be achieved. All attempts at a pinacol cyclization or an intramolecular 6-exo-tet epoxide opening were unsuccessful because of an unfavorable A(1,3) strain inherent in the molecule.
报道了两种构建(-)-FR901483氮杂三环十二烷骨架的方法。两条路线均利用格氏试剂加成到N-酰基吡啶鎓盐上以确定C-6位的绝对立体化学，并通过高度非对映选择性的共轭烯丙基化反应以优异的产率在天然产物的C-1位形成季碳中心。尽管所需的多取代哌啶中间体是区域和立体选择性制备的，但C-8/C-9键连接性的构建未能实现。由于分子中固有的不利的A(1,3)张力，所有进行频哪醇环化或分子内6-外向-四环氧化物开环的尝试均未成功。
