RESUMEN
The cycloisomerization of enynes catalyzed by Pd(OAc)2 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 1H 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)2 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.
RESUMEN
The development of regioselective anti-Markovnikov alkene's hydroamination is a long-standing goal in catalysis. The [Rh(COD)(DPEphos)](+) complex is the most general and regioselective group 9 catalyst for such a process. The reaction mechanism for intermolecular hydroamination of alkenes catalyzed by [Rh(DPEphos)](+) complex is analyzed by means of DFT calculations. Hydroamination (alkene vs. amine activation routes) as well as oxidative amination pathways are analyzed. According to the computational results the operating mechanism can be generally described by alkene coordination, amine nucleophilic addition, proton transfer through the metal center and reductive elimination steps. The mechanism for the formation of the oxidative amination side product goes via a ß-elimination after the nucleophilic addition and metal center protonation steps. The origin of the regioselectivity for the addition process (Markovnikov vs. anti-Markovnikov additions) is shown to be not charge but orbitally driven. Remarkably, η(2) to η(1) slippage degree on the alkene coordination mode is directly related to the regioselective outcome.