Organocatalytic Kinetic Resolution Cascade Reactions: New Mechanistic and Stereochemical Manifold in Diphenyl Prolinol Silyl Ether Catalysis
Organocatalytic Kinetic Resolution Cascade Reactions: New Mechanistic and Stereochemical Manifold in Diphenyl Prolinol Silyl Ether Catalysis
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DOI：
10.1002/chem.201104029
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发表时间：
2012-08-01
影响因子：
4.3
通讯作者：
Brenner-Moyer, Stacey E.
中科院分区：
文献类型：
--
作者：
McGarraugh, Patrick G.;Johnston, Ryne C.;Brenner-Moyer, Stacey E.
本文报道了一种新的级联反应，该反应涉及亚胺催化的分子内氧杂迈克尔加成，然后是烯胺催化的分子间迈克尔加成。该级联反应在一锅反应中生成对映体纯的、高度官能化的四氢吡喃和四氢呋喃，综合收率高达99%该级联反应由二芳基脯氨醇甲硅烷基醚催化，所述二芳基脯氨醇甲硅烷基醚是一类特殊的催化剂。这些级联反应的立体化学结果是前所未有的。计算研究表明，这种立体化学的结果来自非经典的亲电体和基板之间的氢键相互作用，并从熵的考虑preorganization。前所未有的配置的级联产品，结合计算模型，揭示了第一次，不对称诱导二芳基脯氨醇甲硅烷基醚催化剂并不总是完全试剂控制。立体化学结果也来自于通过烯胺催化的分子间反应的β-立构中心的动力学拆分或动态动力学拆分。这一前所未有的有机级联反应机制可能适用于二芳基脯氨醇甲硅烷基醚催化的级联反应，其中亚胺和烯胺催化的步骤都是分子间的，这是一种不发达的级联反应类型。
A new cascade reaction involving an iminium-catalyzed intramolecular oxa-Michael addition followed by an enamine-catalyzed intermolecular Michael addition is reported herein. This cascade reaction generates enantiopure, highly functionalized tetrahydropyrans and tetrahydrofurans in a one-pot reaction and in up to 89?% combined yield and up to 99?% ee. This cascade reaction is catalyzed by diaryl prolinol silyl ethers, which are a privileged class of catalysts. The stereochemical outcome of these cascade reactions is unprecedented. Computational studies indicate that this stereochemical outcome arises from nonclassical hydrogen-bonding interactions between the electrophile and the substrate, and from entropic considerations of preorganization. The unprecedented configurations of the cascade products, combined with the computational models, reveal for the first time that asymmetric induction by diaryl prolinol silyl ether catalysts is not always exclusively reagent controlled. The stereochemical outcome also arises from a kinetic resolution or dynamic kinetic resolution of the beta-stereocenter through an enamine-catalyzed intermolecular reaction. This unprecedented organocascade reaction mechanism may be adaptable to diaryl prolinol silyl ether-catalyzed cascade reactions, in which both the iminium- and enamine-catalyzed steps are intermolecular, an underdeveloped type of cascade reaction.