Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom.
J Am Chem Soc. 2022 Dec 14;144(49):22451-22457. doi: 10.1021/jacs.2c11367. Epub 2022 Dec 1.
Amines featuring an adjacent stereocenter are important building blocks, and recent years have seen remarkable growth in methods forming these via prochiral α-amino radical intermediates. However, very few can exert control over the newly formed stereocenter. We disclose a strategy to overcome this in the context of one of the most widely used radical carbon-carbon bond forming reactions, the Giese reaction. Incorporation of a removable basic heteroarene into the substrate enables a network of attractive noncovalent interactions between a phosphoric acid catalyst, the subsequently formed α-amino radical, and the Giese acceptor, allowing the catalyst to exert control during the C-C bond forming step. Deprotection of the products leads to analogues of γ-aminobutyric acid. We anticipate that this strategy will be applicable to other asymmetric radical transformations in which catalyst control is presently challenging.
具有相邻立体中心的胺是重要的构建模块，近年来，通过前手性α-氨基自由基中间体形成这些化合物的方法有了显著的发展。然而，很少有方法能够控制新形成的立体中心。我们在最广泛使用的自由基碳-碳键形成反应之一，即 Giese 反应的背景下，披露了一种克服这一问题的策略。在底物中引入可去除的碱性杂环芳烃，使得磷酸催化剂、随后形成的α-氨基自由基和 Giese 受体之间形成了一个有吸引力的非共价相互作用网络，从而使催化剂在 C-C 键形成步骤中能够发挥控制作用。产物的脱保护得到γ-氨基丁酸的类似物。我们预计，该策略将适用于其他不对称自由基转化反应，目前这些反应中的催化剂控制具有挑战性。
