Kiriakidi Sofia, Nieto Faza Olalla, Kolocouris Antonios, López Carlos Silva
Department of Medicinal Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens Panepistimioupolis Zografou, Athens, 15771, Greece.
Org Biomol Chem. 2017 Jul 19;15(28):5920-5926. doi: 10.1039/c7ob01275f.
The formation of chiral heterocycles via cycloisomerization reactions of allene derivatives has gained relevance due to their associated efficiency and atom-economy. The only drawback that keeps these reactions away from being routine synthetic strategies is the control in the regioselectivity (most often 5-endo vs. 6-endo). In this work, we computationally explore the experimental chemistry reported by Krause using N-hydroxy-α-aminoallenes and hydroxylamine ethers as substrates and provide a rationale for the different reactivity observed. The drastic effects observed experimentally when changing the nature of the gold catalyst have also been studied mechanistically. These results are expected to help in the design of improved regioselective protocols for the formation of medium sized chiral heterocycles from allene substrates.
通过丙二烯衍生物的环异构化反应形成手性杂环，因其相关的效率和原子经济性而受到关注。使这些反应无法成为常规合成策略的唯一缺点是区域选择性的控制（最常见的是5-内型与6-内型）。在这项工作中，我们通过计算探索了克劳斯报道的以N-羟基-α-氨基丙二烯和羟胺醚为底物的实验化学，并为观察到的不同反应性提供了理论依据。还从机理上研究了改变金催化剂性质时实验观察到的剧烈影响。这些结果有望有助于设计出改进的区域选择性方案，用于从丙二烯底物形成中等大小的手性杂环。
