Wang Xing-Zhen, Huang Hong-Gui, Liu Wen-Bo
Hubei Research Center of Fundamental Science-Chemistry, Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric Optoelectronic Materials, and College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
Org Lett. 2024 Sep 6;26(35):7324-7329. doi: 10.1021/acs.orglett.4c02443. Epub 2024 Aug 22.
Transition metal-catalyzed [2 + 2 + 2] cycloaddition of nitriles and two alkynes is an efficient method for assembling pyridines. However, examples employing palladium catalysis have rarely been disclosed, and the processes of reactivity and selectivity remain unclear. We report here a palladium/copper dual metal-catalyzed [2 + 2 + 2] cycloaddition of diynyl-tethered malononitriles and terminal alkynes to synthesize densely substituted pyridines. This method features a good substrate scope, synthetically useful yields, and perfect regioselectivity. The derivatization of the pyridine products demonstrates the potential application of this method in synthesizing heterocycles and as ligands in photocatalysis. Preliminary mechanistic studies suggest that the reaction undergoes aza-oxidative cycloaddition of Pd(0) with nitrile and alkyne, followed by alkyne insertion and reductive elimination. The presence of copper is crucial to its reactivity and regioselectivity.
过渡金属催化的腈与两个炔烃的[2 + 2 + 2]环加成反应是合成吡啶的一种有效方法。然而，采用钯催化的例子很少被公开，其反应性和选择性过程仍不清楚。我们在此报告一种钯/铜双金属催化的二炔基连接的丙二腈与末端炔烃的[2 + 2 + 2]环加成反应，用于合成高度取代的吡啶。该方法具有良好的底物范围、合成上有用的产率和完美的区域选择性。吡啶产物的衍生化证明了该方法在合成杂环以及作为光催化中的配体方面的潜在应用。初步机理研究表明，该反应经历了Pd(0)与腈和炔烃的氮杂氧化环加成反应，随后是炔烃插入和还原消除反应。铜的存在对其反应性和区域选择性至关重要。
