Remote-Stereocontrol in Dienamine Catalysis: Z-Dienamine Preferences and Electrophile-Catalyst Interaction Revealed by NMR and Computational Studies.
Remote-Stereocontrol in Dienamine Catalysis: Z-Dienamine Preferences and Electrophile-Catalyst Interaction Revealed by NMR and Computational Studies.
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DOI：
10.1021/jacs.6b04008
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发表时间：
2016-08
影响因子：
15
通讯作者：
A. Seegerer;Johnny Hioe;Michael M Hammer;Fabio Morana;Patrick J. W. Fuchs;R. Gschwind
中科院分区：
文献类型：
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作者：
A. Seegerer;Johnny Hioe;Michael M Hammer;Fabio Morana;Patrick J. W. Fuchs;R. Gschwind
远程立体控制的催化在设计和理解方面提出了特殊的挑战。一个著名的例子是二烯胺催化，尽管第二个双键的屏蔽不足，但报道了高ee值。特别是对于第二个双键的Z/E比可变的二烯胺，ee值与其结构没有相关性，因此，我们研究了SN型反应中二烯胺中间体的结构、热力学和动力学。NMR研究表明，如果使用大的亲电试剂，优选的二烯胺构象提供了有效的屏蔽。在SCS-MP2/CBS-水平的理论和实验数据的二烯胺形成的计算显示动力学偏好的Z-异构体的第二个双键和缓慢的异构化对优先选择的E-异构体。通过改变亲电试剂的浓度来调节速率决定步骤，可以观察到二烯胺的转化。与亲电试剂，更快的反应Z-比E-异构体的实验观察。计算证实了这些结果通过关联ee值的三种催化剂的亲电攻击的动力学，并揭示了CH-π和堆积相互作用的过渡态的意义。从而首次对二烯胺γ-功能化反应的远程立体控制有了全面的认识，并对“Z/E-困境”作出了解释。庞大的催化剂子系统和大的亲电试剂的组合提供了一个面的屏蔽，并导致E/Z-二烯胺在亲核攻击中从另一面的不同反应性。形成Z-二烯胺的动力学偏好及其不利的热力学支持高ee值。
Catalysis with remote-stereocontrol provides special challenges in design and comprehension. One famous example is the dienamine catalysis, for which high ee values are reported despite insufficient shielding of the second double bond. Especially for dienamines with variable Z/E-ratios of the second double bond, no correlations to the ee values are found. Therefore, the structures, thermodynamics, and kinetics of dienamine intermediates in SN-type reactions are investigated. The NMR studies show that the preferred dienamine conformation provides an effective shielding if large electrophiles are used. Calculations at SCS-MP2/CBS-level of theory and experimental data of the dienamine formation show kinetic preference for the Z-isomer of the second double bond and a slow isomerization toward the thermodynamically preferred E-isomer. Modulations of the rate-determining step, by variation of the concentration of the electrophile, allow the conversion of dienamines to be observed. With electrophiles, a faster reaction of Z- than of E-isomers is observed experimentally. Calculations corroborate these results by correlating ee values of three catalysts with the kinetics of the electrophilic attack and reveal the significance of CH-π and stacking interactions in the transition states. Thus, for the first time a comprehensive understanding of the remote stereocontrol in γ-functionalization reactions of dienamines and an explanation to the "Z/E-dilemma" are presented. The combination of bulky catalyst subsystems and large electrophiles provides a shielding of one face and causes different reactivities of E/Z-dienamines in nucleophilic attacks from the other face. Kinetic preferences for the formation of Z-dienamines and their unfavorable thermodynamics support high ee values.