Department of Chemistry, South University of Science and Technology of China, 518055, Shenzhen, China.
Nat Commun. 2018 Jan 15;9(1):227. doi: 10.1038/s41467-017-02231-7.
The development of a general catalytic method for the direct and stereoselective construction of cyclopropanes bearing highly congested vicinal all-carbon quaternary stereocenters remains a formidable challenge in chemical synthesis. Here, we report an intramolecular radical cyclopropanation of unactivated alkenes with simple α-methylene group of aldehydes as C1 source via a Cu(I)/secondary amine cooperative catalyst, which enables the single-step construction of bicyclo[3.1.0]hexane skeletons with excellent efficiency, broad substrate scope covering various terminal, internal alkenes as well as diverse (hetero)aromatic, alkenyl, alkyl-substituted geminal alkenes. Moreover, this reaction has been successfully realized to an asymmetric transformation, providing an attractive approach for the construction of enantioenriched bicyclo[3.1.0]hexanes bearing two crucial vicinal all-carbon quaternary stereocenters with good to excellent enantioselectivity. The utility of this method is illustrated by facile transformations of the products into various useful chiral synthetic intermediates. Preliminary mechanistic studies support a stepwise radical process for this formal [2 + 1] cycloaddition.
在化学合成中，开发一种通用的催化方法，用于直接和立体选择性地构建具有高度拥挤的毗邻全碳季立体中心的环丙烷，仍然是一个艰巨的挑战。在这里，我们报告了一种通过 Cu(I)/仲胺协同催化剂实现的未活化烯烃与醛的简单 α-亚甲基的分子内环丙基化反应，该反应通过单步反应有效地构建了双环[3.1.0]己烷骨架，具有广泛的底物范围，包括各种末端、内部烯烃以及各种（杂）芳基、烯基、二取代的偕二烯基。此外，该反应已经成功地实现了不对称转化，为构建具有两个关键毗邻全碳季立体中心的对映富集双环[3.1.0]己烷提供了一种有吸引力的方法，具有良好到优异的对映选择性。该方法的实用性通过产物易于转化为各种有用的手性合成中间体得到了说明。初步的机理研究支持了这种形式的[2 + 1]环加成的逐步自由基过程。
