Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis
Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis
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N-杂环卡宾催化烯烃的非对映选择性自由基氨酰化
DOI：
10.1021/jacs.2c11209
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发表时间：
2022
影响因子：
15
通讯作者：
Jiannan Zhao
中科院分区：
文献类型：
--
作者：
Wen-Deng Liu;Woojin Lee;Hanyu Shu;Chuyu Xiao;Huiwei Xu;Xiangyang Chen;Kendall N. Houk;Jiannan Zhao
通过基于共价的有机催化，自由基介导的反应已经取得了重大进展。在这里，我们展示了通过 N-杂环卡宾 (NHC) 催化生成亚胺基和酰胺基自由基，从而实现三取代烯烃的非对映选择性氨酰化。与光氧化还原催化不同，从去质子化的 Breslow 中间体到 O-芳基羟胺的单电子转移会产生 NHC 结合的羰基自由基，该自由基与前手性 C 中心自由基发生非对映控制的交叉偶联。这种操作简单的方法提供了一种直接获得各种具有邻位立体中心的吡咯啉和恶唑烷酮杂环的方法（77个例子，高达>19:1d.r.）。酰基噻唑鎓盐的电化学研究支持了我们的反应设计并强调了 Breslow 型衍生物的还原能力。对该有机催化系统的详细计算分析表明，自由基-自由基偶联是速率决定步骤，其中自由基中间体之间的 π-π 堆积相互作用巧妙地控制了非对映选择性。
There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation of trisubstituted alkenes. Different from photoredox catalysis, single electron transfer from the deprotonated Breslow intermediate toO-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with the prochiral C-centered radical. This operationally simple method provides a straightforward access to a variety of pyrroline and oxazolidinone heterocycles with vicinal stereocenters (77 examples, up to >19:1 d.r.). Electrochemical studies of the acyl thiazolium salts support our reaction design and highlight the reducing ability of Breslow-type derivatives. A detailed computational analysis of this organocatalytic system suggests that radical–radical coupling is the rate-determining step, in which π–π stacking interaction between the radical intermediates subtly controls the diastereoselectivity.