Catalytic enantioselective desymmetrizing functionalization of alkyl radicals via Cu(i)/CPA cooperative catalysis
Catalytic enantioselective desymmetrizing functionalization of alkyl radicals via Cu(i)/CPA cooperative catalysis
复制标题
通过 Cu(i)/CPA 协同催化对烷基自由基进行催化对映选择性去对称官能化
DOI：
10.1038/s41929-020-0439-8
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发表时间：
2020-03-16
期刊：
影响因子：
37.8
通讯作者：
Liu, Xin-Yuan
中科院分区：
文献类型：
--
作者：
Cheng, Yong-Feng;Liu, Ji-Ren;Liu, Xin-Yuan
与丰富的方法相比，不对称官能化的烷基在反应位点产生立体中心，催化的对映选择性dessymmetrizing官能化的烷基锻造多个立体中心，包括远离反应位点的位置，具有高的对映体和非对映体选择性仍然在很大程度上未被探索。这种反应的主要挑战是开壳烷基自由基的高反应性。在这里，我们描述了一种策略，以解决这一挑战：使用铜（II）磷酸盐立即与原位生成的反应性烷基自由基物种，创造一个紧凑和有限的手性微环境，有效的立体控制。利用这一策略，我们开发了一种通用的、高效的催化烯键连1，3-二醇的不对称官能化反应。它提供了各种带有多个立体中心的四氢呋喃和类似物，具有非常高的对映体和非对映体控制水平。密度泛函理论计算和机理实验揭示了一个反应机制，涉及对映体决定外层C-O键的形成步骤。
In contrast with abundant methods for the asymmetric functionalization of alkyl radicals to generate stereogenic centres at reaction sites, catalytic enantioselective desymmetrizing functionalization of alkyl radicals for forging multiple stereocentres-including positions that are remote from the reaction sites-with both high enantio- and diastereoselectivity remains largely unexplored. The major challenge for such reactions is the high reactivity of open-shell alkyl radicals. Here, we describe a strategy to address this challenge: the use of Cu(ii) phosphate to immediately associate with the in situ-generated reactive alkyl radical species, creating a compact and confined chiral microenvironment for effective stereocontrol. With this strategy, we have developed a general and efficient catalytic enantioselective desymmetrizing functionalization of alkene-tethered 1,3-diols. It provides various tetrahydrofurans and analogues bearing multiple stereocentres with remarkably high levels of enantio- and diastereocontrol. Density functional theory calculations and mechanistic experiments revealed a reaction mechanism involving an enantiodetermining outer-sphere C-O bond formation step.