中科院罗三中团队揭示了手性伯胺/酮协同催化过氧化氢不对称α羟基化反应。 相关研究成果发表在2021年1月5日出版的国际学术期刊《美国化学会志》。

羰基、有机胺是有机催化中的“阴/阳”两面，同时能够互相激活和转化。因此当作为共催化剂时，这两种分子能够相互反应和结合，进而消除单独的反应活性。氨基催化和羰基催化虽然在许多重要的催化策略中得到了广泛的应用，但并不能很好地共存，因此，胺/羰基双催化的协同作用在本质上仍是未知的。

该文报道了一种伯胺-酮协同双催化方法，用于β-酮羰基与H2O2的不对称α-羟基化反应。除了参与典型的烯胺催化循环外，还发现手性伯胺催化剂与酮催化剂协同作用，通过从原位生成的酮亚胺（ketimine）得到恶唑烷中间体活化H2O2分子。最终，这种烯胺-恶氮杂环丙烷的偶联促进了几种β-酮羰基的高度可控的α-羟基化反应，具有良好的产率和对映选择性。

值得注意的是，肽酰酰胺或手性酯的后期羟基化也可以实现高立体选择性。除了操作简单和温和的条件外，这种协同的胺/酮催化方法还为过氧化氢的催化活化提供了一种新的策略，并扩展了包括这种具有挑战性的典型的胺和羰基催化的领域。

附：英文原文

Title: Chiral Primary Amine/Ketone Cooperative Catalysis for Asymmetric α-Hydroxylation with Hydrogen Peroxide

Author: Mao Cai, Kaini Xu, Yuze Li, Zongxiu Nie, Long Zhang, Sanzhong Luo

Issue&Volume: January 5, 2021

Abstract: Carbonyls and amines are yin and yang in organocatalysis as they mutually activate and transform each other. These intrinsically reacting partners tend to condense with each other, thus depleting their individual activity when used together as cocatalysts. Though widely established in many prominent catalytic strategies, aminocatalysis and carbonyl catalysis do not coexist well, and, as such, a cooperative amine/carbonyl dual catalysis remains essentially unknown. Here we report a cooperative primary amine and ketone dual catalytic approach for the asymmetric α-hydroxylation of β-ketocarbonyls with H2O2. Besides participating in the typical enamine catalytic cycle, the chiral primary amine catalyst was found to work cooperatively with a ketone catalyst to activate H2O2 via an oxaziridine intermediate derived from an in-situ-generated ketimine. Ultimately, this enamine–oxaziridine coupling facilitated the highly controlled α-hydroxylation of several β-ketocarbonyls in excellent yield and enantioselectivity. Notably, late-stage hydroxylation for peptidyl amide or chiral esters can also be achieved with high stereoselectivity. In addition to its operational simplicity and mild conditions, this cooperative amine/ketone catalytic approach also provides a new strategy for the catalytic activation of H2O2 and expands the domain of typical amine and carbonyl catalysis to include this challenging transformation.

DOI: 10.1021/jacs.0c11787

Source: https://pubs.acs.org/doi/10.1021/jacs.0c11787