Romain Ramozzi

The ONIOM Method and Its Applications

Lung Wa Chung,† W. M. C. Sameera,‡ Romain Ramozzi,‡ Alister J. Page, Miho Hatanaka,‡ Galina P. Petrova, Travis V. Harris,‡,⊥ Xin Li, Zhuofeng Ke, Fengyi Liu, Hai-Bei Li, Lina Ding, and Keiji Morokuma*,‡ †Department of Chemistry, South University of Science and Technology of China, Shenzhen 518055, China ‡Fukui Institute for Fundamental Chemistry, Kyoto University, 34-4 Takano Nishihiraki-cho, Sakyo, Kyoto 606-8103, Japan Newcastle Institute for Energy and Resources, The University of Newcastle, Callaghan 2308, Australia Faculty of Chemistry and Pharmacy, University of Sofia, Bulgaria Boulevard James Bourchier 1, 1164 Sofia, Bulgaria Department of Chemistry, State University of New York at Oswego, Oswego, New York 13126, United States State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China Key Laboratory of Macromolecular Science of Shaanxi Province, School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, Shaanxi 710119, China School of Ocean, Shandong University, Weihai 264209, China School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001, China

Challenging 50 Years of Established Views on Ugi Reaction: A Theoretical Approach

The Ugi reaction is one of the most famous multicomponent couplings, and its efficiency is still explained by the original mechanism suggested by Ugi in the 60s. This article aims to present a thorough theoretical study of this reaction. It describes how the imine is activated and how the new stereogenic center is formed. Our calculations strongly suggest alternatives to some commonly accepted features, such as the reversibility of the intermediate steps, and temper the nature of the driving force of the reaction.

The physical origin of large covalent–ionic resonance energies in some two-electron bonds

This study uses valence bond (VB) theory to analyze in detail the previously established finding that alongside the two classical bond families of covalent and ionic bonds, which describe the electron-pair bond, there exists a distinct class of charge-shift bonds (CS-bonds) in which the fluctuation of the electron pair density plays a dominant role. Such bonds are characterized by weak binding, or even a repulsive, covalent component, and by a large covalent-ionic resonance energy RE(cs) that is responsible for the major part, or even for the totality, of the bonding energy. In the present work, the nature of CS-bonding and its fundamental mechanisms are analyzed in detail by means of a VB study of some typical homonuclear bonds (H-H, H3C-CH3, H2N-NH2, HO-OH, F-F, and Cl-Cl), ranging from classical-covalent to fully charge-shift bonds. It is shown that CS-bonding is characterized by a covalent dissociation curve with a shallow minimum situated at long interatomic distances, or even a fully repulsive covalent curve. As the atoms that are involved in the bond are taken from left to right or from bottom to top of the periodic table, the weakening effect of the adjacent bonds or lone pairs increases, while at the same time the reduced resonance integral, that couples the covalent and ionic forms, increases. As a consequence, the weakening of the covalent interaction is gradually compensated by a strengthening of CS-bonding. The large RE(cs) quantity of CS-bonds is shown to be an outcome of the mechanism necessary to establish equilibrium and optimum bonding during bond formation. It is shown that the shrinkage of the orbitals in the covalent structure lowers the potential energy, V, but excessively raises the kinetic energy, T, thereby tipping the virial ratio off-balance. Subsequent addition of the ionic structures lowers T while having a lesser effect on V, thus restoring the requisite virial ratio (T/-V = 1/2). Generalizing to typically classical covalent bonds, like H-H or C-C bonds, the mechanism by which the virial ratio is obeyed during bond formation is primarily orbital shrinkage, and therefore the charge-shift resonance energy has only a small corrective effect. On the other hand, for bonds bearing adjacent lone pairs and/or involving electronegative atoms, like F-F or Cl-Cl, the formation of the bond corresponds to a large increase of kinetic energy, which must be compensated for by a large participation or covalent-ionic mixing.

The Biginelli Reaction Is a Urea-Catalyzed Organocatalytic Multicomponent Reaction

The recently developed artificial force induced reaction (AFIR) method was applied to search systematically all possible multicomponent pathways for the Biginelli reaction mechanism. The most favorable pathway starts with the condensation of the urea and benzaldehyde, followed by the addition of ethyl acetoacetate. Remarkably, a second urea molecule catalyzes nearly every step of the reaction. Thus, the Biginelli reaction is a urea-catalyzed multicomponent reaction. The reaction mechanism was found to be identical in both protic and aprotic solvents.

RhIII-Catalyzed C(sp3)H Bond Activation by an External Base Metalation/Deprotonation Mechanism: A Theoretical Study

The C(sp(3) )uf8ffH bond activation of 8-methylquinoline followed by alkyne insertion catalyzed by a Rh(III) complex has been studied by using density functional theory (DFT) calculations. Contrary to common belief, the Cuf8ffH bond activation of methylquinoline does not occur by the traditional intramolecular concerted metalation/deprotonation (CMD) mechanism but by an external base CMD mechanism. The use of free acetate or copper(II) acetate as base permits the Cuf8ffH activation step, as observed experimentally. However, the following insertion is possible only if copper(II) acetate is used. The insertion followed by metathesis occurs via a cationic Rh(III) complex and is irreversible, which ensures the efficiency of the entire process. Therefore the use of copper is crucial for completing the catalytic cycle. The present work should help to rationalize the origins of the experimental results described in the literature.

A valence bond view of isocyanides' electronic structure

High level Valence Bond calculations support a predominantly carbenic electronic structure for isocyanides, with a secondary zwitterionic character, despite their linear geometry. This geometry results from the significant energetic stabilization due to nitrogen π lone pair donation. Results are not changed by substitution or solvation effects.

Revisiting the Passerini Reaction Mechanism: Existence of the Nitrilium, Organocatalysis of Its Formation, and Solvent Effect

The Passerini reaction mechanism is revisited using high-level DFT calculations. Contrary to the common belief, the nitrilium intermediate is found to be stable in solution and its formation is rate-determining. The present results point out that this step is catalyzed by a second carboxylic acid molecule, as the subsequent Mumm rearrangement is. The solvent effect on the reaction rate was investigated. In a protic solvent like methanol, hydrogen bonds are responsible of the increasing barrier of the rate-determining step, compared to the commonly used solvent, the dichloromethane.

Mechanism of Metal-Free C–H Activation of Branched Aldehydes and Acylation of Alkenes Using Hypervalent Iodine Compound: A Theoretical Study

The mechanism of the C-H activation of aldehydes and the succeeding acylation of an alkene using a hypervalent iodine reagent is investigated by theoretical calculations. In contrast to the initial proposed mechanism, the present calculations show that the hypervalent iodine is the initiator of the radical reaction. The formation of acyl radical is rate-determining, and the resulting radical acts as the chain carrier. The kinetic isotope effect (KIE) of deuterated aldehyde, as well as other experimental observations, can now be rationalized from the newly proposed mechanism.

Substituent Effects in Ugi–Smiles Reactions

In a recent communication, we described the mechanism of the well-known Ugi-type reactions with a model system (J. Org. Chem. 2012, 77, 1361-1366). Herein, focusing on the Ugi-Smiles coupling, we study the effects of each of the four reactants on the energy profile to further explain the experimental results. The variations observed with different carbonyl compounds rely on their influence on the formation of the aryl-imidate, whereas the variations on the amine preferentially affect the Smiles rearrangement. The effect of substituents on the phenol derivative is seen upon both aryl-imidate formation and the rearrangement. The effect of the isocyanide substituents is less pronounced.

Predicting new Ugi-smiles couplings: a combined experimental and theoretical study.

Following our previous mechanistic studies of multicomponent Ugi-type reactions, theoretical calculations have been performed to predict the efficiency of new substrates in Ugi-Smiles couplings. First, as predicted, 2,4,6-trichlorophenol experimentally gave the corresponding aryl-imidate. Theoretical predictions of nitrosophenols as good acidic partners were then successfully confirmed by experiments. In the latter case, the reaction offers a new access to benzimidazoles.