Considering the structural importance of 2,6-disubstituted and 2,2,6-trisubstituted tetrahydropyran motifs, two novel types of cascade reactions have been developed to address the challenges of synthetic efficiency, high stereoselectivity and construction of a diaryl quaternary stereogenic carbon center. A single BINOL-derived chiral phosphoric acid catalyst enabled the asymmetric aldehyde-allylboration and subsequent intramolecular oxa-Michael addition or intermolecular variant of oxa-Pictet–Spengler reactions with high to excellent yields (up to 93%), diastereoselectivities (up to >20 : 1 dr) and enantioselectivities (up to 99% ee). The origin of the stereochemical induction was understood via chair-like 6-membered transition states and DFT calculations, which suggested that the thermodynamically favored 2,2,6-trisubstituted THPs were obtained through the kinetically controlled attack of indole on the Si-face of the oxocarbenium ion intermediate.

中文翻译：

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手性多取代四氢吡喃通过手性磷酸的级联不对称醛烯丙基化/氧代环化实现手性多取代四氢吡喃的模块化组装


考虑到 2,6-二取代和 2,2,6-三取代四氢吡喃基序的结构重要性，已经开发了两种新型的级联反应，以应对合成效率、高立体选择性和二芳基季叔立体碳中心构建的挑战。单个 BINO 衍生的手性磷酸催化剂实现了不对称的醛-烯丙基硼化和随后的分子内 oxa-Michael 加成或 oxa-Pictet-Spengler 反应的分子间变体，具有高产率（高达 93%）、非对映选择性（高达 >20 ： 1 dr）和对映选择性（高达 99% ee）。立体化学诱导的起源是通过椅子状 6 元过渡态和 DFT 计算来理解的，这表明热力学上有利的 2,2,6-三取代 THP 是通过吲哚对氧碳烯离子中间体 Si 面的动力学控制攻击获得的。