Rapid total syntheses utilizing "supersilyl" chemistry.
Rapid total syntheses utilizing "supersilyl" chemistry.
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DOI：
10.1002/anie.201007210
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发表时间：
2011-03-07
影响因子：
16.6
通讯作者：
Yamamoto, Hisashi
中科院分区：
文献类型：
--
作者：
Albert, Brian J.;Yamaoka, Yousuke;Yamamoto, Hisashi
尽管100多年的研究已经证明，羟醛反应是构建复杂分子，特别是天然产物的最基本和最有效的方法之一，但它的潜力还没有得到充分的认识。[1]聚酮是一类天然产物，为化学家提供了丰富的分子结构和具有生物意义的化合物的来源。[2]聚酮通常含有1，3-多元醇基元，不出所料，Aldol反应一直是获得这些结构的首选方法。[1，2]然而，不幸的是，最具选择性的Aldol产品提供的是酮或酯[3]而不是醛。因此，已报道的仿生路线在每次迭代中需要额外的保护和氧化还原步骤，从而使得制备长链聚酮过于冗长(氧化还原经济性差)。[4]因此，对一锅聚醛醇级联反应的兴趣增加。[5]虽然已经报道了几种优雅的立体选择性方法，但由于羟醛或羟基酮的环化，所有方法不可避免地在第二次Aldol反应后停止。如果通过原位生成的封闭变异体使侧基成为非亲核基团，则这种环化反应可能被阻断，这一点很重要，它将提供醛2作为产物。我们最近报道了第一个高产率的三重羟醛缩合反应(方案1A)。[6]这种级联反应导致高1，3-立体诱导，由极大的三(三甲基硅基)硅基(超硅基)基团产生，这也阻碍了不希望发生的聚合。[7]在1，5-立体选择性的羟醛缩合反应中使用大体积的β-硅氧基甲基酮3与醛的反应产生具有高非对映选择性的4或5(方案1B)。[8]重要的是，所有三种1，3，5-三醇立体异构体可以很容易地从4和5制备。[8]这两种策略的使用将允许容易地合成复杂的1，3-多元醇和螺酮。在这里，我们报道了用这些方法快速全合成EBC-23和聚甲氧基-1-烯烃13。
Although more than 100 years of study have demonstrated that the aldol reaction is one of the most fundamental and effective methods for the construction of complex molecules, in particular natural products, its full potential has not been realized.[1] Polyketides, a family of natural products, have provided chemists with a rich source of molecular architectures and biologically significant compounds.[2] Polyketides often contain the 1, 3-polyol motif, and unsurprisingly the aldol reaction has been the preferred method to access these structures.[1, 2] Unfortunately, however, the most selective aldol products afford ketones or esters [3] and not aldehydes. Thus, the reported biomimetic routes require additional protection and redox steps for each iteration, thus making the preparation of long-chain polyketides excessively lengthy (poor redox economy).[4] Therefore, interest in one-pot polyaldol cascade reactions has increased.[5] Although, several elegant stereoselective approaches have been reported, all the methods inevitably stop after the second aldol reaction because of the cyclization of the hydroxyaldehydes or-ketones. This cyclization could be blocked if the pendant hydroxy groups were rendered non-nucleophilic by an in situ generated blocking variant, which, importantly, would afford aldehydes 2 as products. We recently reported the first high-yielding triple aldol reaction (Scheme 1A).[6] This cascade results in high 1, 3-stereoinduction, generated from the extreme bulk of the tris (trimethylsilyl) silyl (supersilyl) group, which also retards undesired polymerization.[7]The use of the bulky β-silyloxy methyl ketones 3 in 1, 5-stereoselective aldol reactions with aldehydes produces 4 or 5 with high diastereoselectivity (Scheme 1B).[8] Importantly, all three 1, 3, 5-triol stereoisomers can easily be prepared from 4 and 5.[8] The utilization of both of these strategies would allow for the facile synthesis of complex 1, 3-polyols and spiroketals. Herein we report the rapid total syntheses of EBC-23 and polymethoxy-1-alkene 13 by these approaches.
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影响因子：
15
作者：
Dong, Lin;Gordon, Victoria A.;Williams, Craig M.
通讯作者：
Williams, Craig M.
影响因子：
3.6
作者：
CARMELI, S;MOORE, RE;SUZUKI, M
通讯作者：
SUZUKI, M
影响因子：
16.6
作者：
Casas, J;Engqvist, M;Córdova, A
通讯作者：
Córdova, A
影响因子：
3.8
作者：
MYNDERSE, JS;MOORE, RE
通讯作者：
MOORE, RE
影响因子：
1.8
作者：
NAKATA, T;SUENAGA, T;OISHI, T
通讯作者：
OISHI, T