Aggarwal Varinder K, Grange Emma
School of Chemistry, University of Bristol, Cantock's Close, Bristol BS8 1TS, UK.
Chemistry. 2005 Dec 23;12(2):568-75. doi: 10.1002/chem.200500693.
The reaction of ester-stabilized sulfonium ylides with cyclopentenone to give (+)-5 ((1S,5R,6S)-ethyl 2-oxobicyclo[3.1.0]hexane-6-carboxylate), an important precursor to the pharmacologically important compound (+)-LY354740, has been studied using chiral sulfides operating in both catalytic (sulfide, Cu(acac)2, ethyl diazoacetate, 60 degrees C) and stoichiometric modes (sulfonium salt, base, room temperature). It was found that the reaction conditions employed had a major influence over both diastereo- and enantioselectivity. Under catalytic conditions, good enantioselectivity with low diastereoselectivity was observed, but under stoichiometric conditions low enantioselectivity with high diastereoselectivity was observed. When the stoichiometric reactions were conducted at high dilution, diastereoselectivity was reduced. This indicated that base-mediated betaine equilibration was occurring (which is slow relative to ring closure at high dilution). Based on this model, conditions for achieving high enantioselectivity were established as follows: use of a preformed ylide, absence of base, hindered ester (to reduce ylide-mediated betaine equilibration), and low concentration. Under these conditions high enantioselectivity (95 % ee) was achieved, albeit with low diastereocontrol. Our model for selectivity has been applied to other sulfonium ylide mediated cyclopropanation reactions and successfully accounts for the diastereoselectivity observed in all such reported reactions to date.
酯稳定的硫叶立德与环戊烯酮反应生成(+)-5 ((1S,5R,6S)-乙基 2-氧代双环[3.1.0]己烷-6-羧酸酯)，这是药理活性重要化合物(+)-LY354740的重要前体，已使用手性硫化物在催化模式（硫化物、Cu(acac)₂、重氮乙酸乙酯，60℃）和化学计量模式（硫鎓盐、碱，室温）下进行了研究。发现所采用的反应条件对非对映选择性和对映选择性都有重大影响。在催化条件下，观察到良好的对映选择性但非对映选择性较低，而在化学计量条件下，观察到对映选择性较低但非对映选择性较高。当化学计量反应在高稀释度下进行时，非对映选择性降低。这表明发生了碱介导的甜菜碱平衡（相对于高稀释度下的闭环反应较慢）。基于该模型，实现高对映选择性的条件如下：使用预先形成的叶立德、不存在碱、使用位阻酯（以减少叶立德介导的甜菜碱平衡）和低浓度。在这些条件下实现了高对映选择性（95% ee），尽管非对映控制较低。我们的选择性模型已应用于其他硫叶立德介导的环丙烷化反应，并成功解释了迄今为止所有此类报道反应中观察到的非对映选择性。
