Chiral Phosphoric Acid Catalyzed Enantioselective Synthesis of α-Tertiary Amino Ketones from Sulfonium Ylides
Chiral Phosphoric Acid Catalyzed Enantioselective Synthesis of α-Tertiary Amino Ketones from Sulfonium Ylides
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手性磷酸催化锍叶立德对映选择性合成α-叔氨基酮
DOI：
10.1021/jacs.0c07210
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发表时间：
2020-08-19
影响因子：
15
通讯作者：
Sun, Jianwei
中科院分区：
文献类型：
--
作者：
Guo, Wengang;Luo, Yuzheng;Sun, Jianwei
在此，我们公开了一种用于合成手性α-氨基酮的新催化不对称方法，该方法对于不易获得的无环α-三级酮的情况特别有用。通过质子化-胺化序列，我们的方法代表了α-羰基锍叶立德（一种有吸引力的重氮羰基替代品）罕见的不对称H-杂原子键插入。手性磷酸催化温和的分子间 C-N 键形成，具有优异的效率和对映选择性。该产品是其他重要手性胺衍生物的前体，包括药物分子和手性配体。对映选择性是通过胺化步骤中的动态动力学拆分来控制的，而不是通过初始质子化来控制。该过程为其他相关插入反应的开发开辟了新平台。
Herein we disclose a new catalytic asymmetric approach for the synthesis of chiral alpha-amino ketones, which is particularly useful for the less accessible acyclic alpha-tertiary cases. By a protonation-amination sequence, our approach represents a rare asymmetric H-heteroatom bond insertion by alpha-carbonyl sulfonium ylides, an attractive surrogate of diazocarbonyls. The mild intermolecular C-N bond formation was catalyzed by chiral phosphoric acids with excellent efficiency and enantioselectivity. The products are precursors to other important chiral amine derivatives, including drug molecules and chiral ligands. The enantioselectivity was controlled by dynamic kinetic resolution in the amination step, rather than the initial protonation. This process opens up a new platform for the development of other related insertion reactions.