Enantioselective Silicon-Directed Nazarov Cyclization
Enantioselective Silicon-Directed Nazarov Cyclization
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DOI：
10.1021/jacs.1c01194
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发表时间：
2021-04-28
影响因子：
15
通讯作者：
Zhou, Qi-Lin
中科院分区：
文献类型：
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作者：
Cao, Jin;Hu, Meng-Yang;Zhou, Qi-Lin
Nazarov电环化反应是一种简便、广泛应用的环戊烯酮合成方法。在过去的几十年里，该反应的催化不对称版本已被广泛研究，但用于控制双键位置的策略限制了产物的取代基模式，从而限制了该反应的合成应用。本文报道了一种刘易斯酸和一种手性Bronsted酸协同催化的高对映选择性的硅导向Nazarov反应。我们使用这种方法合成的手性环戊烯酮通常不能通过其他催化的对映选择性反应，包括以前报道的对映选择性Nazarov环化的方法。二烯酮底物中的硅基稳定了中间体的β-碳阳离子，从而确定了产物中双键的位置。机理研究表明，刘易斯酸和布朗斯台德酸的组合协同激活的二烯酮底物和反应的对映体选择性源于手性布朗斯台德酸促进的烯醇中间体的质子转移反应。
The Nazarov electrocyclization reaction is a convenient, widely used method for construction of cyclopentenones. In the past few decades, catalytic asymmetric versions of the reaction have been extensively studied, but the strategies used to control the position of the double bond limit the substituent pattern of the products and thus the synthetic applications of the reaction. Herein, we report highly enantioselective silicon-directed Nazarov reactions which were cooperatively catalyzed by a Lewis acid and a chiral Bronsted acid. The chiral cyclopentenones we synthesized using this method generally cannot be obtained by means of other catalytic enantioselective reactions, including previously reported methods for enantioselective Nazarov cyclization. The silicon group in the dienone substrate stabilized the beta-carbocation of the intermediate, thereby determining the position of the double bond in the product. Mechanistic studies suggested that the combination of Lewis and Bronsted acids synergistically activated the dienone substrate and that the enantioselectivity of the reaction originated from a chiral Bronsted acid promoted proton transfer reaction of the enol intermediate.