Lu Qi-Tao, Du Yuan-Bo, Xu Meng-Meng, Xie Pei-Pei, Cai Quan
Department of Chemistry, Research Center for Molecular Recognition and Synthesis, Fudan University, Shanghai 200433, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
J Am Chem Soc. 2024 Aug 7;146(31):21535-21545. doi: 10.1021/jacs.4c04852. Epub 2024 Jul 26.
Electrophilic addition of alkenes is a textbook reaction that plays a pivotal role in organic chemistry. In the past decades, catalytic asymmetric variants of this important type of reaction have witnessed great achievements by the development of novel catalytic systems. However, enantioselective aza-electrophilic additions of unactivated alkenes, which could provide a transformative strategy for the preparation of synthetically significant nitrogen-containing compounds, still remain a formidable challenge. Herein, we have developed unprecedented Au(I)/NHC-catalyzed asymmetric aza-electrophilic additions of unactivated 1,1-disubstituted styrenes by the utilization of readily available dialkyl azodicarboxylates as electrophilic nitrogen sources. Based on this approach, a series of transformations, including [2 + 2] cycloaddition, intermolecular 1,2-oxyamination, and several types of intramolecular hydrazination-induced cyclizations, have been realized. These transformations provide a previously unattainable platform for the divergent synthesis of hydrazine derivatives, which could also be converted to other nitrogen-containing chiral synthons. Experimental and computational studies support the idea that carbocation intermediates are involved in reaction pathways.
烯烃的亲电加成是有机化学中一个经典的反应，在有机化学中起着关键作用。在过去几十年里，通过开发新型催化体系，这类重要反应的催化不对称变体取得了巨大成就。然而，未活化烯烃的对映选择性氮亲电加成反应，可为合成具有重要意义的含氮化合物提供一种变革性策略，但仍然是一个巨大的挑战。在此，我们利用易得的偶氮二羧酸二烷基酯作为亲电氮源，开发了前所未有的金（I）/氮杂环卡宾催化的未活化1,1 - 二取代苯乙烯的不对称氮亲电加成反应。基于此方法，实现了一系列转化反应，包括[2 + 2]环加成、分子间1,2 - 氧胺化反应以及几种类型的分子内肼化诱导环化反应。这些转化反应为肼衍生物的发散合成提供了一个前所未有的平台，这些肼衍生物还可以转化为其他含氮手性合成子。实验和计算研究支持反应途径中涉及碳正离子中间体这一观点。
