Computational ligand design in enantio- and diastereoselective ynamide [5+2] cycloisomerization.
Computational ligand design in enantio- and diastereoselective ynamide [5+2] cycloisomerization.
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DOI：
10.1038/ncomms10109
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发表时间：
2016-01-05
影响因子：
16.6
通讯作者：
Anderson EA
中科院分区：
文献类型：
--
作者：
Straker RN;Peng Q;Mekareeya A;Paton RS;Anderson EA
过渡金属可以催化环状有机分子的立体选择性合成，这是一个高度原子效率的过程，称为环异构化。已经开发了许多非对映选择性（底物立体控制）和对映选择性（催化剂立体控制）环化异构化。然而，不对称环异构化，其中手性催化剂指定的立体化学结果的环化一个单一的对映异构体基板，无论其固有的偏好是未知的。在这里，我们将展示如何结合理论和实验方法，使设计的高反应性铑催化剂的立体选择性环异构化的crosside-vinylcyclopropanes [5.3.0]-azabicycles。我们首先建立高度非对映选择性环异构化使用的非手性催化剂，然后探索亚磷酰胺络合铑催化剂的对映选择性的变体，理论研究发现一个意想不到的反应途径，其中的亚磷酰胺的电子结构显着影响反应速率和对映选择性。使用最佳理论设计的配体观察到两者的显着增强，这使得在匹配和失配的催化剂-底物设置中的双立体分化环异构化成为可能。 使用手性催化剂来克服非对映选择性过程的固有立体化学结果是一项具有挑战性的任务。在这里，作者使用理论和实验来开发环异构化，其中对映选择性由配体的电子性质驱动，而不管反应的固有非对映选择性。
Transition metals can catalyse the stereoselective synthesis of cyclic organic molecules in a highly atom-efficient process called cycloisomerization. Many diastereoselective (substrate stereocontrol), and enantioselective (catalyst stereocontrol) cycloisomerizations have been developed. However, asymmetric cycloisomerizations where a chiral catalyst specifies the stereochemical outcome of the cyclization of a single enantiomer substrate—regardless of its inherent preference—are unknown. Here we show how a combined theoretical and experimental approach enables the design of a highly reactive rhodium catalyst for the stereoselective cycloisomerization of ynamide-vinylcyclopropanes to [5.3.0]-azabicycles. We first establish highly diastereoselective cycloisomerizations using an achiral catalyst, and then explore phosphoramidite-complexed rhodium catalysts in the enantioselective variant, where theoretical investigations uncover an unexpected reaction pathway in which the electronic structure of the phosphoramidite dramatically influences reaction rate and enantioselectivity. A marked enhancement of both is observed using the optimal theory-designed ligand, which enables double stereodifferentiating cycloisomerizations in both matched and mismatched catalyst–substrate settings. Using a chiral catalyst to override the innate stereochemical outcome of a diastereoselective process is a challenging task. Here, the authors use theory and experiment to develop a cycloisomerization where the enantioselectivity is driven by the electronic nature of the ligand regardless of the reaction's inherent diastereoselectivity.