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 β-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.

In this work, we computationally address, from DFT calculations, mechanistic issues of the recently described hydroamination reactions catalyzed by (carbene) gold(I) complexes that use hydrazine as N-nucleophile. We have explored the hydrohydrazination of alkynes, alkenes, and allenes using three gold− carbene catalysts reported by Bertrand's and Hashmi's groups. Aspects such as the associative or dissociative nature of the ligand exchange between hydrazine and the substrate, the generation of the catalytically active π-complex, the inner-or outer-sphere mechanism for the nucleophilic attack, the nitrogen to carbon proton transfer or the relative importance of the ligand substitution, the nucleophile addition, and the proton transfer barriers in the catalytic cycle are analyzed in light of the DFT results, taking into account the nature of the carbene ligand and the substrate. The study can provide background for the design of further hydroamination reactions using simple small N-nucleophiles.

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.

The reaction mechanism and regioselectivity for the gold­(I)-catalyzed hydroamination reaction of terminal alkenes are analyzed by means of density functional theory (DFT) calculations. The influence of the nature of the olefin as well as the ligand present in the gold­(I) catalyst on the regioselectivity is investigated. The anti-Markovnikov addition is preferred for some alkenes, particularly those having cyclopropyl or good electron-withdrawing groups in their structures. The regioselectivity of the process is quantitatively analyzed with the help of state-of-the-art computational methods, namely, the activation strain model (ASM) of reactivity and natural orbitals for chemical valence (NOCV) method. It is found that the back-bonding interactions in the initially formed π-complex are directly related to the Gibbs energy barrier difference between the Markonikov and anti-Markovnikov additions. It can be concluded that the coordination mode of the initial π-complex ultimately controls the regioselectivity outcome of the transformation.

The reaction mechanism for the hydration of internal and terminal allenes catalyzed by [Au(NHC)] + is analyzed by means of DFT calculations. Several reaction pathways for generating the two possible regioisomers were evaluated. Direct addition on coordinated allenes or to an intermediate with a σ-allylic cation structure as suggested for the Au(I)-catalyzed hydroamination of allenes were considered. The isomerization between both regioisomeric products catalyzed by the same Au(I) catalyst was also investigated as suggested for hydroalkoxylation of allenes. The regioselectivity of the reaction predicted by computation agrees with experiment for both terminal and internal allenes. The presence of alkyl or aryl substituents introduces differences in the reaction mechanism for the hydration process.Special Issue: In Honor of the Career of Ernesto Carmona