Origin of the relative stereoselectivity of the β-lactam formation in the Staudinger reaction
Origin of the relative stereoselectivity of the β-lactam formation in the Staudinger reaction
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DOI：
10.1021/ja056711k
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发表时间：
2006-05-10
影响因子：
15
通讯作者：
Xu, Jiaxi
中科院分区：
文献类型：
--
作者：
Jiao, Lei;Liang, Yong;Xu, Jiaxi
β -内酰胺形成的相对（顺式、反式）立体选择性是Staudinger反应的关键问题之一。虽然人们已经做了许多尝试来解释和预测立体化学的结果，但立体选择性的起源仍然不清楚。我们提出了一个基于反应产物的顺/反比动力学分析的模型来解释相对立体选择性。这些结果来自于详细的哈米特分析。利用环亚胺对烯酮取代基的电子效应进行了研究，发现其立体选择性不能简单地归结为力矩电子模型。根据我们的研究结果，相对立体选择性的起源可以描述为：(1)立体选择性的产生是两性离子中间体中亚胺部分的异构化与直接闭合环之间竞争的结果；(2)环闭合步骤很可能是烯酸酯在亚胺基团上的分子内亲核加成，这一过程明显受到烯酮和亚胺取代基的电子效应的影响；(3)给电子烯酮取代基和吸电子亚胺取代基加速了直接闭合环，有利于顺式- β -内酰胺的形成；吸电子烯酮取代基和吸电子亚胺取代基减缓了直接闭合环，有利于反式- β -内酰胺的形成；(4)取代基对异构化的电子效应是影响立体选择性的次要因素。
The relative (cis, trans) stereoselectivity of the beta-lactam formation is one of the critical issues in the Staudinger reaction. Although many attempts have been made to explain and to predict the stereochemical outcomes, the origin of the stereoselectivity remains obscure. We are proposing a model that explains the relative stereoselectivity based on a kinetic analysis of the cis/trans ratios of reaction products. The results were derived from detailed Hammett analyses. Cyclic imines were employed to investigate the electronic effect of the ketene substituents, and it was found that the stereoselectivity could not be simply attributed to the torquoelectronic model. Based on our results, the origin of the relative stereoselectivity can be described as follows: (1) the stereoselectivity is generated as a result of the competition between the direct ring closure and the isomerization of the imine moiety in the zwitterionic intermediate; (2) the ring closure step is most likely an intramolecular nucleophilic addition of the enolate to the imine moiety, which is obviously affected by the electronic effect of the ketene and imine substituents; (3) electron-donating ketene substituents and electron-withdrawing imine substituents accelerate the direct ring closure, leading to a preference for cis-beta-lactam formation, while electron-withdrawing ketene substituents and electron-donating imine substituents slow the direct ring closure, leading to a preference for trans-beta-lactam formation; and (4) the electronic effect of the substituents on the isomerization is a minor factor in influencing the stereoselectivity.