Modulating Stereoselectivity through Electrostatic Interactions in a SPINOL-Phosphoric Acid-Catalyzed Synthesis of 2,3-Dihydroquinazolinones
Modulating Stereoselectivity through Electrostatic Interactions in a SPINOL-Phosphoric Acid-Catalyzed Synthesis of 2,3-Dihydroquinazolinones
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DOI：
10.1021/acscatal.0c02578
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发表时间：
2020-10-16
期刊：
影响因子：
12.9
通讯作者：
Wheeler, Steven E.
中科院分区：
文献类型：
--
作者：
Laconsay, Croix J.;Seguin, Trevor J.;Wheeler, Steven E.
手性磷酸因其在许多不对称催化反应中的优异性能而受到广泛关注。然而，调节这些催化剂的立体选择性的方法还没有完全阐明。本文利用密度泛函理论计算探讨了用spinol衍生的手性磷酸催化不对称合成2,3-二氢喹唑啉酮对映体选择性的来源（ACS catalal . 2013, 3,2244）。我们发现，该反应的对映选择性是在有机级联序列的分子内胺加成步骤中决定的，并受到底物与催化剂芳基的差异非共价相互作用以及CH中心点中心点中心点O和nh中心点中心点中心点O与催化剂磷酸核的相互作用的调节。最值得注意的是，我们证明了后一种相互作用的强度是由它们在催化剂产生的静电环境中的位置调制的。这为通过调整静电相互作用来精确控制有机催化反应的选择性提供了明确的证据。
Chiral phosphoric acids have received considerable attention because of their excellent performance in many asymmetric catalytic reactions. However, the full breadth of means by which the stereoselectivity of these catalysts can be tuned has not been fully elucidated. Herein, the origin of enantioselectivity in a catalytic asymmetric synthesis of 2,3-dihydroquinazolinones using SPINOL-derived chiral phosphoric acids (ACS Catal. 2013, 3, 2244) is explored using density functional theory computations. We show that the enantioselectivity of this reaction is determined during the intramolecular amine addition step of an organocascade sequence and is modulated by differential noncovalent interactions of the substrate with the aryl groups of the catalyst as well as CH center dot center dot center dot O and NH center dot center dot center dot O interactions with the phosphate core of the catalyst. Most notably, we demonstrate that the strength of these latter interactions is modulated by their position within the electrostatic environment created by the catalyst. This provides clear evidence of the ability to precisely control the selectivity of an organocatalyzed reaction through the tuning of electrostatic interactions.