Chemistry Research Laboratory, University of Oxford , 12 Mansfield Road, Oxford OX1 3TA, U.K.
Departament de Química, Universitat Autònoma de Barcelona , 08193 Cerdanyola del Vallès, Spain.
J Am Chem Soc. 2017 Jul 26;139(29):10104-10114. doi: 10.1021/jacs.7b05436. Epub 2017 Jul 12.
The cycloisomerization of enynes catalyzed by Pd(OAc) and bis-benzylidene ethylenediamine (bbeda) is a landmark methodology in transition-metal-catalyzed cycloisomerization. However, the mechanistic pathway by which this reaction proceeds has remained unclear for several decades. Here we describe mechanistic investigations into this reaction using enynamides, which deliver azacycles with high regio- and stereocontrol. Extensive H NMR spectroscopic studies and isotope effects support a palladium(II) hydride-mediated pathway and reveal crucial roles of bbeda, water, and the precise nature of the Pd(OAc) pre-catalyst. Computational studies support these mechanistic findings and lead to a clear picture of the origins of the high stereocontrol that can be achieved in this transformation, as well as suggesting a novel mechanism by which hydrometalation proceeds.
钯（OAc）和双苄叉乙二胺（bbeda）催化的烯炔环异构化是过渡金属催化环异构化中的一个里程碑式的方法。然而，几十年来，该反应的反应机理仍不清楚。在这里，我们使用烯酰胺对该反应进行了机理研究，烯酰胺可以高区域和立体选择性地得到氮杂环。广泛的 H NMR 光谱研究和同位素效应支持钯（II）氢化物介导的途径，并揭示了 bbeda、水和 Pd（OAc）前催化剂的精确性质的关键作用。计算研究支持这些机理发现，并清楚地说明了在这种转化中可以实现的高立体控制的起源，同时也提出了一种新的氢金属化反应机制。
