Stereoselective Construction of Seven-Membered Rings with an All-Carbon Quaternary Center by Direct Tiffeneau-Demjanov-type Ring Expansion
Stereoselective Construction of Seven-Membered Rings with an All-Carbon Quaternary Center by Direct Tiffeneau-Demjanov-type Ring Expansion
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DOI：
10.1021/ja900941k
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发表时间：
2009-05-13
影响因子：
15
通讯作者：
Maruoka, Keiji
中科院分区：
文献类型：
--
作者：
Hashimoto, Takuya;Naganawa, Yuki;Maruoka, Keiji
在环己酮的C-C键上插入一个亚甲基单元是一种潜在的、直接的构建七元碳环的方法。在这一竞技场中，一种特别吸引人但在很大程度上未开发的方法是重氮烷与刘易斯酸活化的环己酮的亲核加成，随后伴随着氮的挤出的环膨胀（直接的Tiffeneau-Demjanov型环膨胀）。我们的主要发现是前所未有的插入α-烷基重氮乙酸环己酮及其杂类似物，产生一个全碳季中心的七元环。基于这一发现，开发了取代的环己酮的高度非对映选择性扩环，从容易获得的材料开始，在单一操作中提供具有1，4-季-叔、1，4-季-季或1，3，5-季-叔-叔立体中心的七元环。产物的立体化学结果可以很容易地从起始环己酮的构象预测。对映体富集的产物也可以通过使用（-）-苯基薄荷基α-烷基重氮乙酸酯来获得。
Insertion of one methylene unit into the C-C bond of cyclohexanones is a potentially useful, straightforward method for the construction of seven-membered carbocycles. An especially appealing but largely unexplored method in this arena is the nucleophilic addition of diazoalkanes to the Lewis acid-activated cyclohexanones and subsequent ring expansion accompanied by the extrusion of nitrogen (direct Tiffeneau-Demjanov-type ring expansion). Our primary finding is the unprecedented insertion of alpha-alkyldiazoacetates to cyclohexanone and its heteroanalogues, generating seven-membered rings with one all-carbon quaternary center. On the basis of this finding, highly diastereoselective ring expansion of substituted cyclohexanones was developed, furnishing seven-membered rings with 1,4-quaternary-tertiary, 1,4-quaternary-quaternary, or 1,3,5-quaternary-tertiary-tertiary stereogenic centers in a single operation starting from readily available materials. The stereochemical outcome of the product can be easily predicted from the conformation of starting cyclohexanones. Enantioenriched products could be also accessed by the use of (-)-phenylmenthyl alpha-alkyldiazoacetates.