Feliu Maseras

Direct Arylation of Arene C−H Bonds by Cooperative Action of NHCarbene−Ruthenium(II) Catalyst and Carbonate via Proton Abstraction Mechanism

Direct functionalization of sp2 C−H bonds via ortho diarylation of 2-pyridyl benzene with arylbromides was achieved using ruthenium(II) catalysts containing a RuCl2(NHC) unit and generated from [RuCl2(arene)]2 and two types of NHC precursors, pyrimidinium and benzimidazolium salts, in the presence of Cs2CO3. DFT calculations from RuCl2(NHC)(2-pyridylbenzene) show that a proton abstraction mechanism, on cooperative actions of both the coordinated base and the Ru(II) center, is favored via a 13.7 kcal·mol-1 exothermic process affording an orthometalated intermediate with a 2.009 A Ru−C bond.

Computational Perspective on Pd-Catalyzed C–C Cross-Coupling Reaction Mechanisms

Palladium-catalyzed C-C cross-coupling reactions (Suzuki-Miyaura, Negishi, Stille, Sonogashira, etc.) are among the most useful reactions in modern organic synthesis because of their wide scope and selectivity under mild conditions. The many steps involved and the availability of competing pathways with similar energy barriers cause the mechanism to be quite complicated. In addition, the short-lived intermediates are difficult to detect, making it challenging to fully characterize the mechanism of these reactions using purely experimental techniques. Therefore, computational chemistry has proven crucial for elucidating the mechanism and shaping our current understanding of these processes. This mechanistic elucidation provides an opportunity to further expand these reactions to new substrates and to refine the selectivity of these reactions. During the past decade, we have applied computational chemistry, mostly using density functional theory (DFT), to the study of the mechanism of C-C cross-coupling reactions. This Account summarizes the results of our work, as well as significant contributions from others. Apart from a few studies on the general features of the catalytic cycles that have highlighted the existence of manifold competing pathways, most studies have focused on a specific reaction step, leading to the analysis of the oxidative addition, transmetalation, and reductive elimination steps of these processes. In oxidative addition, computational studies have clarified the connection between coordination number and selectivity. For transmetalation, computation has increased the understanding of different issues for the various named reactions: the role of the base in the Suzuki-Miyaura cross-coupling, the factors distinguishing the cyclic and open mechanisms in the Stille reaction, the identity of the active intermediates in the Negishi cross-coupling, and the different mechanistic alternatives in the Sonogashira reaction. We have also studied the closely related direct arylation process and highlighted the role of an external base as proton abstractor. Finally, we have also rationalized the effect of ligand substitution on the reductive elimination process. Computational chemistry has improved our understanding of palladium-catalyzed cross-coupling processes, allowing us to identify the mechanistic complexity of these reactions and, in a few selected cases, to fully clarify their mechanisms. Modern computational tools can deal with systems of the size and complexity involved in cross-coupling and have a continuing role in solving specific problems in this field.

Merging Sustainability with Organocatalysis in the Formation of Organic Carbonates by Using CO2as a Feedstock

The use of phenolic compounds as organocatalysts is discussed in the context of the atom-efficient cycloaddition of carbon dioxide to epoxides, forming useful cyclic organic carbonate products. The presence and cooperative nature of adjacent phenolic groups in the catalyst structure results in significantly enhanced catalytic efficiencies, allowing these CO(2) fixation reactions to operate efficiently under virtually ambient conditions. The cooperative effect has also been studied by computational methods. Furthermore, when the cycloaddition reactions are carried out on a larger scale and under solvent-free conditions, further enhancements in activity are observed, combined with the advantageous requirement of reduced loadings of the binary organocatalyst system. The reported system is among one of the mildest and most effective metal-free catalysts for this conversion and contributes to a much more sustainable development of organic carbonate production; this feature has not been the main focus of previous contributions in this area.

Metal–Arene Interactions in Dialkylbiarylphosphane Complexes of Copper, Silver, and Gold

Dialkylbiphenylphosphane-Au(I) complexes exhibit only weak metal-arene interactions with the covering arene ring. However, the contacts in isoleptic Ag(I) and Cu(I) complexes are shorter than the limiting values of 3.03 A (Ag(I)) and 2.83 A (Cu(I)). Strong metal-arene interactions were also found in the two Ag(I) aquo complexes and in two acetonitrile--Cu(I) complexes with dialkylbiphenylphosphane ligands. Arene-Ag(I) complexes with these bulky phosphane ligands show the strongest Ag(I)--arene bonds known.

Selective Homogeneous and Heterogeneous Gold Catalysis with Alkynes and Alkenes: Similar Behavior, Different Origin

The development of new sustainable chemical processes requires the implementation of ultra-selective reaction processes. The enormous selectivity found for gold-based catalysts when applied in several reactions has opened new frontiers. For instance, the selective activation of alkynes is a common feature for both homogeneous and heterogeneous gold catalysts. Herein, we employ experimental and theoretical methods to assess the similarities and differences in the performance of homogeneous and heterogeneous gold catalysts. Alkynophilicity, the selective activation of alkynes, is found to have a thermodynamic origin in the heterogeneous case and a kinetic one for homogeneous catalysis. Complex enyne rearrangements require the more active homogeneous (single gold) catalyst because it has more electrophilic character than its heterogeneous (nanoparticle) counterpart.

Gold(I)-catalyzed intermolecular hydroalkoxylation of allenes: a DFT study.

The mechanistic and regiochemical aspects in the Au(I)-catalyzed intermolecular hydroalkoxylation of allenes have been studied computationally. The most favorable pathway is nucleophilic attack of an Au(I)-coordinated allene, which occurs irreversibly. An Au(I)-catalyzed mechanism is proposed that allows the facile interconversion of regioisomeric allylic ether products. The regioisomers are connected via a stabilized diether intermediate with a C-Au sigma-bond, which successfully explains the observed regioselectivity for the thermodynamic product.

Computational approaches to asymmetric synthesis

Theoretical chemistry has been successfully used as a powerful tool to obtain valuable insight into the mechanism and the origin of enantioselectivity in several asymmetric reactions of high interest. In this Perspective article, the application of QM, MM and QM/MM methods to the rationalization of electronic and steric effects upon enantioselectivity is briefly reviewed, considering some representative contributions of the last three decades.

A General Mechanism for the Copper- and Silver-Catalyzed Olefin Aziridination Reactions: Concomitant Involvement of the Singlet and Triplet Pathways

The olefin aziridination reactions catalyzed by copper and silver complexes bearing hydrotris(pyrazolyl)borate (Tp(x)) ligands have been investigated from a mechanistic point of view. Several mechanistic probe reactions were carried out, specifically competition experiments with p-substituted styrenes, stereospecificity of olefins, effects of the radical inhibitors, and use of a radical clock. Data from these experiments seem to be contradictory, as they do not fully support the previously reported concerted or stepwise mechanisms. But theoretical calculations have provided the reaction profiles for both the silver and copper systems with different olefins to satisfy all experimental data. A mechanistic proposal has been made on the basis of the information that we collected from experimental and theoretical studies. In all cases, the reaction starts with the formation of a metal-nitrene species that holds some radical character, and therefore the aziridination reaction proceeds through the radical mechanism. The silver-based systems however hold a minimum energy crossing point (MECP) between the triplet and closed-shell singlet surfaces, which induce the direct formation of the aziridines, and stereochemistry of the olefin is retained. In the case of copper, a radical intermediate is formed, and this intermediate constitutes the starting point for competition steps involving ring-closure (through a MECP between the open-shell singlet and triplet surfaces) or carbon-carbon bond rotation, and explains the loss of stereochemistry with a given substrate. Overall, all the initially contradictory experimental data fit in a mechanistic proposal that involves both the singlet and the triplet pathways.

Protonation of transition-metal hydrides: a not so simple process

The protonation of a transition-metal hydride is a formally simple process between a proton donor and a proton acceptor with several potential basic centres. The detailed mechanism is however quite subtle, with multistep reactions and involvement of different intermediates. The process is furthermore very sensitive to the nature of both the proton donor and the transition-metal complex, as well as to the solvent and to the presence and identity of eventual counteranions. This tutorial review summarizes the recent progress in the understanding of the reaction, obtained through the joint application of a number of computational and experimental techniques.

Mechanism of the gold-catalyzed cyclopropanation of alkenes with 1,6-enynes

The gold(I)-catalyzed intermolecular cyclopropanation of alkenes with 1,6-enynes is an electrophilic process, which is mechanistically related to the well-known Simmons–Smith reaction proceeding through zinc carbenoids. This cyclopropanation is stereospecific, even in cases where the reaction was found to proceed stepwise.