大连理工大学Jiannan Zhao团队近日取得一项新成果。经过不懈努力，他们开发出N-杂环卡宾催化的烯烃的非对映选择性自由基氨基酰化反应。该项研究成果发表在2022年11月24日出版的《美国化学会杂志》上。

通过共价基有机催化实现自由基介导的反应已经取得了显著的进展。在该研究中，课题组提出了通过N-杂环卡宾（NHC）催化生成亚胺基和酰胺基自由基，使三取代烯烃实现非对映选择性氨基酰化。与光氧化还原催化不同的是，从去质子化的Breslow中间体到O-芳基羟胺的单电子转移生成一个NHC结合的酮基自由基，它与前手性的C-中心自由基进行非对映控制的交叉偶联。这种操作简单的方法可以直接获得具有邻手性中心的多种吡咯啉和恶唑烷酮杂环化合物（77个例子，高达>19:1 d.r.）。

在进一步研究中，对酰基噻唑盐的电化学研究支持了这一反应设计，并突出了Breslow衍生物的还原能力。对该有机催化体系的详细计算分析表明，自由基-自由基耦合是反应速率的决速步骤，其中自由基中间体之间的π-π堆积相互作用微妙地控制了非对映选择性。

附：英文原文

Title: Diastereoselective Radical Aminoacylation of Olefins through N-Heterocyclic Carbene Catalysis

Author: Wen-Deng Liu, Woojin Lee, Hanyu Shu, Chuyu Xiao, Huiwei Xu, Xiangyang Chen, Kendall N. Houk, Jiannan Zhao

Issue&Volume: November 24, 2022

Abstract: 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 to O-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.

DOI: 10.1021/jacs.2c11209

Source: https://pubs.acs.org/doi/10.1021/jacs.2c11209