Practical and Highly Selective Sulfur Ylide-Mediated Asymmetric Epoxidations and Aziridinations Using a Cheap and Readily Available Chiral Sulfide: Extensive Studies To Map Out Scope, Limitations, and Rationalization of Diastereo- and Enantioselectivities
Practical and Highly Selective Sulfur Ylide-Mediated Asymmetric Epoxidations and Aziridinations Using a Cheap and Readily Available Chiral Sulfide: Extensive Studies To Map Out Scope, Limitations, and Rationalization of Diastereo- and Enantioselectivities
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DOI：
10.1021/ja405073w
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发表时间：
2013-08-14
影响因子：
15
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Illa, Ona;Namutebi, Mariam;Aggarwal, Varinder K.
以单质硫、γ-萜品烯和柠檬烯为原料，一步合成了手性硫醚异硫桉叶素，收率61%。根据实验证据，提出了该反应涉及自由基中间体的机理。介绍了异硫桉叶素在醛的不对称环氧化和亚胺的氮杂环丙烷化反应中的应用。使用简单的方法，已经在广泛的芳香族、脂肪族和α，β-不饱和醛上获得了优异的对映选择性和非对映选择性。在氮杂环丙烷化反应中，对许多亚胺都有很好的对映选择性和非对映选择性。已经提出了机制模型，以合理化观察到的高选择性，这应该使硫化物在合成中使用的信心。在环氧化反应中，甜菜碱形成的可逆性程度决定了非对映选择性和对映选择性。在大多数情况下，基于对反应机理的理解适当调整反应条件能够获得高选择性。在氮杂环丙烷化反应中，甜菜碱的形成是不可逆的，半稳定叶立德和非对映选择性是在甜菜碱形成步骤中确定的，因此变化更大。
The chiral sulfide, isothiocineole, has been synthesized in one step from elemental sulfur, gamma-terpinene, and limonene in 61% yield. A mechanism involving radical intermediates for this reaction is proposed based on experimental evidence. The application of isothiocineole to the asymmetric epoxidation of aldehydes and the aziridination of imines is described. Excellent enantioselectivities and diastereoselectivities have been obtained over a wide range of aromatic, aliphatic, and alpha,beta-unsaturated aldehydes using simple protocols. In aziridinations, excellent enantioselectivities and good diastereoselectivities were obtained for a wide range of imines. Mechanistic models have been put forward to rationalize the high selectivities observed, which should enable the sulfide to be used with confidence in synthesis. In epoxidations, the degree of reversibility in betaine formation dominates both the diastereoselectivity and the enantioselectivity. Appropriate tuning of reaction conditions based on understanding the reaction mechanism enables high selectivities to be obtained in most cases. In aziridinations, betaine formation is nonreversible with semistabilized ylides and diastereoselectivities are determined in the betaine forming step and are more variable as a result.