An Rh 2(OAc)4/Zr-3-I-binol co-catalyzed enantioselective three-component cascade reaction of diazo compounds, ethyl 4-hydroxybutenoate and furfurals has been designed to build complex fused O-heterocycles in a one pot fashion. The reaction was conducted in CH2Cl2 or CHCl3 at ambient temperature with 3 A molecular sieves as an additive. The multi- component process was completed within 3 h to give multi-component products and the following Diels-Alder (DA) cycliza- tion product was observed in the next several hours. It was found that the DA process was slow but could be completed after 7~12 d by standing the crude reaction mixture after evaporating solvent. Following a one-pot epoxidation of the product further increases the molecular complexity to give fused epoxidation products bearing multiple chiral carbon centers. Espe- cially to be noted, all of the products are very easy to be purified by simple recrystallization in mixture solvent of ethyl ace- tate (EA)/petroleum ether (PE, 60~90 ℃) and do not need any column chromatography method. Using the developed method, hydroepoxyisochromene derivatives with up to eight contiguous chiral carbon centers have been readily prepared from simple starting materials with high diastereoselectivity (up to 99/1 dr) and enantioselectivity (up to 99% ee). The abso- lute stereochemistry of product was determined by the single crystal X-ray analysis as a chair conformation with absolute configurations. The possible mechanisms were theoretically investigated by DFT calculation and proposed as an oxonium ylide-trapping three-component reaction subsequently followed with a spontaneous intramolecular Diels-Alder process and an epoxidation at the end. The developed three-component cascade reaction provides a rapid access to the construction of chiral fused polycyclic O-heterocycles with molecular complexity. Keywords multi-component cascade reaction; asymmetric catalysis; molecular complexity; one pot; O-heterocycles

中文翻译：

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用于合成手性官能化羟基异色烯的一锅对映选择性多组分级联反应：快速获取分子复杂性

Rh 2(OAc)4/Zr-3-I-binol 共催化重氮化合物、4-羟基丁烯酸乙酯和糠醛的对映选择性三组分级联反应已被设计用于以单锅方式构建复杂的稠合 O-杂环。该反应在室温下在 CH2Cl2 或 CHCl3 中以 3A 分子筛作为添加剂进行。多组分过程在 3 小时内完成，得到多组分产物，在接下来的几个小时内观察到以下 Diels-Alder (DA) 环化产物。发现DA过程缓慢，但可以在蒸发溶剂后静置粗反应混合物7~12天后完成。在产物的一锅环氧化之后进一步增加了分子复杂性以得到带有多个手性碳中心的稠合环氧化产物。特别要指出的是，所有产品在乙酸乙酯(EA)/石油醚(PE, 60~90 ℃)混合溶剂中通过简单的重结晶很容易纯化，不需要任何柱层析方法。使用所开发的方法，可以从具有高非对映选择性（高达 99/1 dr）和对映选择性（高达 99% ee）的简单起始材料中轻松制备具有多达八个连续手性碳中心的氢化环氧异色烯衍生物。产品的绝对立体化学通过单晶 X 射线分析确定为具有绝对构型的椅子构象。通过 DFT 计算从理论上研究了可能的机制，并提出了氧鎓叶立德捕获三组分反应，随后是自发的分子内 Diels-Alder 过程和最后的环氧化。开发的三组分级联反应为构建具有分子复杂性的手性稠合多环 O-杂环提供了快速途径。关键词多组分级联反应；不对称催化；分子复杂性；一锅；O-杂环