Highly Acidic Conjugate‐Base‐Stabilized Carboxylic Acids Catalyze Enantioselective oxa‐Pictet–Spengler Reactions with Ketals
Highly Acidic Conjugate‐Base‐Stabilized Carboxylic Acids Catalyze Enantioselective oxa‐Pictet–Spengler Reactions with Ketals
复制标题
高酸性缀合物 - 碱 - 稳定的羧酸催化对映选择性氧杂 - Pictet - 与缩酮的 Spengler 反应
DOI：
10.1002/ange.201912677
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发表时间：
2019
影响因子：
--
通讯作者：
Seidel, Daniel
中科院分区：
文献类型：
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作者：
Zhu, Zhengbo;Odagi, Minami;Zhao, Chenfei;Abboud, Khalil A.;Kirm, Helmi Ulrika;Saame, Jaan;Lõkov, Märt;Leito, Ivo;Seidel, Daniel
无环酮衍生的氧代碳正离子作为中间体参与提供有价值产物的许多反应，然而，它们迄今为止一直未能实现旨在不对称催化的努力。我们报道了一种易于获得的手性羧酸催化剂对无环酮衍生的三取代氧代碳正离子的不对称环化施加控制，从而提供了获得含有四取代立体中心的高度对映体富集的二氢吡喃产物的途径。羧酸催化剂的高酸性（其超过众所周知的手性磷酸催化剂TRIP的酸性）主要来源于羧酸酯共辄碱通过分子内阴离子结合到硫脲位点的稳定化。
Acyclic ketone‐derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone‐derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well‐known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion‐binding to a thiourea site.