The Intramolecular Diels-Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is a Stepwise Process.
The Intramolecular Diels-Alder Reaction of Tryptamine-Derived Zincke Aldehydes Is a Stepwise Process.
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DOI：
10.1039/c2sc01072k
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发表时间：
2012
期刊：
影响因子：
8.4
通讯作者：
Houk KN
中科院分区：
文献类型：
--
作者：
Pham HV;Martin DB;Vanderwal CD;Houk KN
计算研究表明，碱介导的分子内Diels-Alder色胺衍生的Zincke醛，作为一个关键步骤，在合成马钱子生物碱norfluorocurarine和士的宁，收益通过逐步途径。实验确定的碱中钾反离子的重要性可以通过其将锌基醛二烯预组织成适合双环化的顺式构象的能力来解释。计算还支持在最后的反应步骤中生成稳定的烯醇化物的热力学重要性。Diels-Alder产物的热环化反应也被发现以逐步的方式进行。
Computational studies show that the base-mediated intramolecular Diels–Alder of tryptamine-derived Zincke aldehydes, used as a key step in the synthesis of the Strychnos alkaloids norfluorocurarine and strychnine, proceeds via a stepwise pathway. The experimentally determined importance of a potassium counterion in the base is explained by its ability to preorganize the Zincke aldehyde diene in an s-cis conformation suitable to bicyclization. Computation also supports the thermodynamic importance of the generation of a stable enolate in the final reaction step. The thermal cycloreversion reaction of the Diels–Alder products is also found to proceed in a stepwise manner.