Regioselective Pd-Catalyzed Synthesis of 2,3,6-Trisubstituted Pyridines from Isoxazolinones.
Regioselective Pd-Catalyzed Synthesis of 2,3,6-Trisubstituted Pyridines from Isoxazolinones.
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DOI：
10.1021/acs.joc.5b01065
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发表时间：
2015-06
期刊：
影响因子：
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通讯作者：
Stefan Rieckhoff;T. Hellmuth;R. Peters
中科院分区：
文献类型：
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作者：
Stefan Rieckhoff;T. Hellmuth;R. Peters
取代吡啶是一种普遍存在的重要杂环。尽管报道了大量的合成方法，但有效的区域选择性制备仍然是一个挑战。在这封信中，我们报告了一种操作简单的方法，它利用了容易获得的异恶唑啉酮。该方案包括Pd（II）催化的c -区域选择性1,4加成到乙烯基酮，然后是Pd(0)催化的转化，该转化被认为是通过乙烯基硝基烯-Pd中间体进行的。氢气和空气都是吡啶生成步骤所必需的，并且可以在高于爆炸上限的比例下使用，从而避免安全问题。这种新策略可以有效、可扩展和实用地获取各种以前未知的2,3,6-三取代吡啶。
Substituted pyridines are prevalent heterocycles of fundamental importance. Their efficient regioselective preparation is often still a challenge despite a large number of reported synthetic methodologies. In this letter we report an operationally simple approach that makes use of readily accessible isoxazolinones. The protocol involves a Pd(II)-catalyzed C-regioselective 1,4-addition to vinylketones, followed by a Pd(0)-catalyzed transformation, which is assumed to proceed via vinylnitrene-Pd intermediates. Both hydrogen and air are necessary for the pyridine formation step and could be employed at ratios above the upper explosive limit thus avoiding a safety issue. This new strategy allows an effective, scalable and practical access to various previously unknown 2,3,6-trisubstituted pyridines.