Odile Eisenstein

• Mason, Ellis Joseph; Saint-Denis, Tyler G.; See, Matthew S.; Chen, Qingchuan; Balazs, Gabor & Raynaud, Christophe [Show all 9 contributors for this article] (2026). Pnictogen Atom Transfer within a Transition Metal Coordination Sphere: Efficient Routes to <i>η</i> ¹ -Phosphaazallene and <i>η</i> ¹ -Arsaazallene Complexes. Inorganic Chemistry Frontiers. ISSN 2052-1545. doi: 10.1039/d6qi02076c. Full text in Research Archive Show summary

  A metal-mediated migration of pnictogen atoms Pn (Pn = P, As) to form phosphaazaallene and arsaazaallene complexes Cp*(CO)(IPr)Ru–Pn=C=N–Xyl results from clean reactions of the ruthenium carbene complex Cp*(XylNC)(IPr)RuCl ( 1 , XylNC...

• Ludwig, Philipp; Clot, Eric; Perutz, Robin N.; Raynaud, Christophe & Eisenstein, Odile (2026). Relations between H–C and M–C bond strengths: influence of the organic ligand and the metal. Coordination chemistry reviews. ISSN 0010-8545. 566. doi: 10.1016/j.ccr.2026.218137. Full text in Research Archive Show summary

  This review describes the thermodynamics of C–H bond activation in various hydrocarbons, especially (poly)fluorinated benzenes, by transition metal complexes through experiments and computational studies with a focus on the latter. Experimental metal‑carbon bond dissociation enthalpies (BDEs), determined relative to an internal reference, were used to establish the relationship between H–C and M–C BDEs. In parallel, bond dissociation enthalpies or energies were computed with DFT methods. For a given metal complex and a set of sufficiently similar organic substrates a linear correlation with a characteristic slope RM-C/H-C was obtained. Since far more H–C BDEs are known than M–C BDEs, these correlations provide a powerful predictive tool. Both experimental and computational studies indicate that the slope is always greater than 1 and quantitatively agree on its value when comparisons could be made, suggesting a systematic thermodynamic preference for cleaving stronger hydrogen‑carbon bonds. The RM-C/H-C value is particularly high for (poly)fluorobenzenes, with the greatest increase in M–C BDE occurring when fluorine atoms are ortho to the M–C bond, as found by experiments. Values of RM-C/H-C almost up to 3 have been reported. The polarity of the M–C bond, greater than that of the H–C bond, is suggested to be the cause of the high value of RM-C/H-C and the associated observed high selectivity in C–H bond activation. Recent experimental studies suggested that Co is more selective than Rh and Ir for C–H bond activation in (poly)fluorobenzenes. A computational study of the thermodynamics of C–H activation in C6FnH6-n (n = 0, 5) by CpM(CO) (M = Co, Rh, Ir) confirms that RM-C/H-C is highest for Co and shows again a relation between RM-C/H-C and the polarity of the M–C bond. Additionally, the RM-C/H-C value is shown to be inversely related to the strength of the M–C bond since the Co–C BDE is the weakest for group 9 transition metals. Further studies are needed to confirm the generality of the finding that 3d transition metal complexes could be more selective in C–H activation than their heavier congeners. Correlations are also found between M–X and H–X (X = O, N) BDEs with slopes varying from 0.9 to 1.4. The ranking of M–X BDEs (M–C < M–N < M–O) is discussed as well as the magnitudes of the correlation slopes that are generally higher for aromatic substituents. Although this review is centred on reactions with thermodynamically controlled product distributions, some reactions are recognized in which kinetically controlled products follow thermodynamics. For all systems, computations appear to provide accurate information and can replace experiments if needed. Prediction of relative bond strengths in many organometallic species from knowledge of bond strengths for cognate organic molecules can be achieved.

• Oliveira, Daniel A. Santos; Silva, Daniela Rodrigues; Braga, Ataualpa A.C.; Guerra, Célia Fonseca; Perutz, Robin N. & Eisenstein, Odile [Show all 7 contributors for this article] (2026). How fluorine substituents strengthen aryl C–H bonds. Chemical Science. ISSN 2041-6520. doi: 10.1039/d6sc01846g. Full text in Research Archive Show summary

  We have investigated the nature and bond dissociation energies (BDEs) of the aromatic C–H bonds in fluorinated benzenes C6R5H (each R can be H or F) using quantitative Kohn–Sham molecular orbital theory and a matching energy decomposition analysis (EDA). The C–H bond becomes stronger as the number of fluorine atoms in the benzene ring increases. This increase in the calculated BDE is additive and most pronounced for ortho-substituted C–H bonds. Our analyses of the C–H bond between Image ID:d6sc01846g-t1.gif and H˙ reveal that a fluorine inductive effect is responsible for this. Fluorine polarizes the closed-shell molecular orbitals of Image ID:d6sc01846g-t2.gif away from the carbon radical center and in this way reduces Pauli repulsion between [C˙] and the H˙ radical, leading to a stronger C–H bond. The ortho effect can be accurately modelled by a combination of Pauli repulsion (main contribution) and orbital interactions. We extend our analysis to other substituents, including ones with the opposite effect on C–H bond strength.

• Bortoli, Marco; Bore, Sigbjørn Løland; Eisenstein, Odile & Cascella, Michele (2025). The influence of the organic residue and the solvent in the Schlenk equilibrium for Grignard reagents in THF. A molecular dynamics study with machine learning potentials. Journal of Catalysis. ISSN 0021-9517. 454. doi: 10.1016/j.jcat.2025.116619. Full text in Research Archive Show summary

  The Schlenk equilibrium is an essential characteristic of the Grignard reagents. However, its quantitative aspects remain poorly understood. In this work, we perform molecular dynamics simulations to characterise how the Schlenk reaction is affected by varying the alkyl R groups (Me, Et, i-Pr, t-Bu). For each R group, the reactivity profiles were obtained through enhanced sampling on fully solvated dinuclear species, leveraging a newly developed machine learning potential trained on ab initio data. While the topologies of the Helmholtz energy maps are qualitatively similar, the energy ranges vary significantly with the R groups. Bulkier R groups disfavour higher solvation of the magnesium centre, with direct implications for the activation and mechanism of the Schlenk exchange. With respect to dichloro-bridged species, the concentrations of monochloro-bridged and separated species increase with the size of R and the degree of solvation. The energy barrier for ligand exchange increases with the size of R, and it is particularly noticeable for R = t-Bu, in agreement with experimental data. As excess solvation of one of the magnesium centres is associated with the most important reaction pathways, it can be deduced that early formation of monochloro-bridged species favours the Cl/R exchange, especially for large R groups. The formation of these species is favoured by higher Mg solvation for small R groups, and by the steric volume of R itself for large R, pointing at a constructive effect of the solvent and R promoting Cl/R exchange. Our study shows that a full characterisation of the speciation of Grignard reagents in solution is possible at reasonable computational costs with machine-learning potentials.

• Manasi, Iva; Bortoli, Marco; Bowron, Daniel T.; Campana, Mario; Hammond, Oliver S. & Headen, Thomas F. [Show all 11 contributors for this article] (2025). Are Grignard Reactions in Deep Eutectic Solvents Interface‐Driven? Angewandte Chemie International Edition. ISSN 1433-7851. 64(42). doi: 10.1002/anie.202513649. Full text in Research Archive Show summary

  Due to their high reactivity, organolithium and organomagnesium addition to ketones is usually performed under inert atmosphere at low temperature. Recent work has shown that, by dissolving the substrate in deep eutectic solvents (DES), these processes can be carried out on the benchtop, in air at room temperature. Surprisingly, the organometallic reagent, added to the DES from an organic solution, works in these conditions and gives better yields than in the standard setup. Here, we investigated acetophenone in a (1:2) choline chloride:glycerol (ChCl:Gly) DES solution by experimental liquid diffraction, neutron reflectometry, NMR, interfacial tension measurements, and by computational modelling. Our data show that this DES is a poor solvent for the ketone and promotes its accumulation at the surface of the liquid or its escape into the organic solvent. Molecular dynamics simulations of Grignard reagent i ‐PrMgCl in the (ChCl:Gly)/tetrahydrofuran biphasic system indicate also preference for its localisation at the interface. These results pinpoint why this combination of solvents promote the reaction, require stirring, and accounts for the lack of rapid decomposition of the organometallic reagents.

• Cascella, Michele; Bore, Sigbjørn Løland & Eisenstein, Odile (2025). The fellowship of the Grignard: 21st century computational tools for hundred-year-old chemistry. Chemical Science. ISSN 2041-6520. 16, p. 8196–8216. doi: 10.1039/d5sc01078k. Full text in Research Archive Show summary

  This perspective begins with the discovery of the Grignard reaction by a graduate student in the last years of the 19th century, followed by describing why it has remained largely unexplained for more than a century. From the summary of what has been achieved, focusing on the computational aspects, it is now clear that further studies of the chemistry of any chemical species that is highly sensitive to solvents, such as Group I and II elements, require a holistic approach that includes the solute and the solvent together. Ab initio molecular dynamics, which meets these requirements, has produced some results but has hit hard limits due to its relatively high computational costs. In these days, it is becoming clear that data-driven methods, including machine learning potentials and simulations driven by quantitative on-the-fly calculation of relevant observables, have the potential to better and more completely explore the very large chemical space associated with the presence of a large number of species in solution. These methodologies have the chance to give the keys to enter the challenging and still poorly explored world of chemical species whose behaviour and reactivity are strongly influenced by the solvent and the experimental conditions.

• Giovanetti, Marinella de; Eliasson, Sondre Hilmar Hopen; Bore, Sigbjørn Løland; Eisenstein, Odile & Cascella, Michele (2024). Morphology of lithium halides in tetrahydrofuran from molecular dynamics with machine learning potentials. Chemical Science. ISSN 2041-6520. doi: 10.1039/d4sc04957h. Full text in Research Archive Show summary

  The preferred structures of lithium halides (LiX, with X = Cl, Br, I) in organic solvents have been the subject of a wide scientific debate, and a large variety of forms has been isolated and characterized by X-ray diffraction. The identified molecular scaffolds for LiX are diverse, often built on (LiX)n rings with a prevalence of rhomboidal arrangements and an appropriate number of solvent or Lewis base molecules coordinating the lithium ions. Much less is known about the structures of LiX in solution, limiting the understanding of the synergistic role of LiX in reactions with various organometallic complexes, as prominently represented by the turbo Grignard reaction. Here, we trained a machine learning potential on ab initio data to explore the complex conformational landscape for systems comprising four LiX moieties in tetrahydrofuran (THF). For all the considered halogens a large number of scaffolds were found at thermally accessible free energy values, indicating that LiX in solution are a diverse ensemble constituted of (LiX)n moieties of various sizes, completed by the appropriate number of coordinating THF. LiCl shows a preference for compact, pseudo-cubane Li4Cl4(THF)4 structures, coexisting with open rings. At concentrations close to the solubility limit, LiCl forms hexagonal structures, in analogy with literature observations on pre-nucleating NaCl. LiBr tends to favour less compact, more solvated aggregates. LiI significantly differs from the two other cases, producing highly solvated, monomeric, dimeric, or linear structures. This study provides a comprehensive view of LiX in organic solvent, revealing dynamical polymorphism that is not easily observable experimentally.

• Eisenstein, Odile (2024). Nucleophilic addition to carbonyl groups from qualitative to quantitative computational studies. A historical perspective. Comptes rendus. Chimie. ISSN 1631-0748. 27, p. 1–15. doi: 10.5802/crchim.298. Full text in Research Archive Show summary

  Nucleophilic addition to carbonyl groups is one of the most important reactions in organic synthesis. In the case of a prochiral carbonyl group, the preference for the addition of a nucleophile to one face of the system leads to unequal amounts of the two possible diastereoisomers. The mechanism of this reaction for various nucleophiles (especially the early main group hydride and the Grignard reagents) and the various noncyclic and cyclic aldehydes or ketones has fascinated computational chemists for nearly 40 years. This article describes the research that has been done on this topic, the incentive for the present author being that she started her research with this topic and is returning to it in recent years.

• Giovanetti, Marinella de; Eliasson, Sondre Hilmar Hopen; Bore, Sigbjørn Løland; Eisenstein, Odile & Cascella, Michele (2024). Morphology of Lithium Halides in Tetrahydrofuran from Molecular Dynamics with Machine Learning Potentials. ChemRxiv. ISSN 2573-2293. doi: 10.26434/chemrxiv-2024-mxjqn. Full text in Research Archive
• Giovanetti, Marinella de; Eliasson, Sondre Hilmar Hopen; Castro, Abril C; Eisenstein, Odile & Cascella, Michele (2023). Morphological Plasticity of LiCl Clusters Interacting with Grignard Reagent in Tetrahydrofuran. Journal of the American Chemical Society. ISSN 0002-7863. 145(30), p. 16305–16309. doi: 10.1021/jacs.3c04238. Full text in Research Archive Show summary

  Ab initio molecular dynamics simulations are used to explore tetrahydrofuran (THF) solutions containing pure LiCl and LiCl with CH3MgCl, as model constituents of the turbo Grignard reagent. LiCl aggregates as Li4Cl4, which preferentially assumes compact cubane-like conformations. In particular, an open-edge pseudotetrahedral frame is promoted by solvent-assisted Li–Cl bond cleavage. Among the Grignard species involved in the Schlenk equilibrium, LiCl prefers to coordinate MgCl2 through μ2-Cl bridges. Using a 1:1 Li:Mg ratio, the plastic tetranuclear LiCl cluster decomposes to a highly solvated mixed LiCl·MgCl2 aggregate with prevalent Li–(μ2-Cl)2–Mg rings and linear LiCl entities. The MgCl2-assisted disaggregation of Li4Cl4 occurs through transient structures analogous to those detected for pure LiCl in THF, also corresponding to moieties observed in the solid state. This study identifies a synergistic role of LiCl for the determination of the compounds present in turbo Grignard solutions. LiCl shifts the Schlenk equilibrium promoting a higher concentration of dialkylmagnesium, while decomposing into smaller, more soluble, mixed Li:Mg:Cl clusters.

• Castro, Abril C; Cascella, Michele; Perutz, Robin N.; Raynaud, Christophe & Eisenstein, Odile (2023). Solid-State 19F NMR Chemical Shift in Square-Planar Nickel-Fluoride Complexes Linked by Halogen Bonds. Inorganic Chemistry. ISSN 0020-1669. 62(12), p. 4835–4846. doi: 10.1021/acs.inorgchem.2c04063. Full text in Research Archive Show summary

  The halogen bond (XB) is a highly directional class of noncovalent interactions widely explored by experimental and computational studies. However, the NMR signature of the XB has attracted limited attention. The prediction and analysis of the solid-state NMR (SSNMR) chemical shift tensor provide useful strategies to better understand XB interactions. In this work, we employ a computational protocol for modeling and analyzing the 19F SSNMR chemical shifts previously measured in a family of square-planar trans NiII-L2-iodoaryl-fluoride (L = PEt3) complexes capable of forming self-complementary networks held by a NiF···I(C) halogen bond [Thangavadivale, V.; Chem. Sci. 2018, 9, 3767−3781]. To understand how the 19F NMR resonances of the nickel-bonded fluoride are affected by the XB, we investigate the origin of the shielding in trans-[NiF(2,3,5,6-C6F4I)(PEt3)2], trans-[NiF(2,3,4,5-C6F4I)(PEt3)2], and trans-[NiF(C6F5)(PEt3)2] in the solid state, where a XB is present in the two former systems but not in the last. We perform the 19F NMR chemical shift calculations both in periodic and molecular models. The results show that the crystal packing has little influence on the NMR signatures of the XB, and the NMR can be modeled successfully with a pair of molecules interacting via the XB. Thus, the observed difference in chemical shift between solid-state and solution NMR can be essentially attributed to the XB interaction. The very high shielding of the fluoride and its driving contributor, the most shielded component of the chemical shift tensor, are well reproduced at the 2c-ZORA level. Analysis of the factors controlling the shielding shows how the highest occupied Ni/F orbitals shield the fluoride in the directions perpendicular to the Ni–F bond and specifically perpendicular to the coordination plane. This shielding arises from the magnetic coupling of the Ni(3d)/F(2p lone pair) orbitals with the vacant σNi–F* orbital, thereby rationalizing the very highly upfield (shielded) resonance of the component (δ33) along this direction. We show that these features are characteristic of square-planar nickel–fluoride complexes. The deshielding of the fluoride in the halogen-bonded systems is attributed to an increase in the energy gap between the occupied and vacant orbitals that are mostly responsible for the paramagnetic terms, notably along the most shielded direction.

• Eisenstein, Odile (2022). From the Felkin-Anh Rule to the Grignard Reaction: an Almost Circular 50 Year Adventure in the World of Molecular Structures and Reaction Mechanisms with Computational Chemistry. Israel Journal of Chemistry (IJC). ISSN 0021-2148. 62. doi: 10.1002/ijch.202100138. Full text in Research Archive Show summary

  This rosarium article relates the adventure started 50 years ago of a computational chemist who was interested in molecules; what are they, what are their shape and how do they react. The story describes results, still valid today, obtained with highly simplified models of chemical reality and elementary computational methods and the gain resulting from the use of better models and more elaborate computational methods. It was necessary to select examples. In this presentation, focus is on hydride and dihydrogen complexes as well as on nucleophiles. Nucleophiles were considered as free hydrides in gas phase at the start of the rosarium while the Grignard reaction is treated with ab initio molecular mechanisms at the end of it.

• Yang, Jian; Postils, Verònica; Lipschutz, Michael I.; Fasulo, Meg; Raynaud, Christophe & Clot, Eric [Show all 8 contributors for this article] (2020). Efficient alkene hydrosilation with bis(8-quinolyl)phosphine (NPN) nickel catalysts. The dominant role of silyl-over hydrido-nickel catalytic intermediates. Chemical Science. ISSN 2041-6520. 11(19), p. 5043–5051. doi: 10.1039/d0sc00997k. Full text in Research Archive Show summary

  A cationic nickel complex of the bis(8-quinolyl)(3,5-di-tert-butylphenoxy)phosphine (NPN) ligand, [(NPN)NiCl]+, is a precursor to efficient catalysts for the hydrosilation of alkenes with a variety of hydrosilanes under mild conditions and low catalyst loadings. DFT studies reveal the presence of two coupled catalytic cycles based on [(NPN)NiH]+ and [(NPN)NiSiR3]+ active species, with the latter being more efficient for producing the product. The preferred silyl-based catalysis is not due to a more facile insertion of alkene into the Ni–Si (vs. Ni–H) bond, but by consistent and efficient conversions of the hydride to the silyl complex.

• Raynaud, Christophe; Norbert-Agaisse, Eliott; James, Brian R. & Eisenstein, Odile (2020). 31P Chemical Shifts in Ru(II) Phosphine Complexes. A Computational Study of the Influence of the Coordination Sphere. Inorganic Chemistry. ISSN 0020-1669. 59, p. 17038–17048. doi: 10.1021/acs.inorgchem.0c02256. Full text in Research Archive Show summary

  The NMR chemical shift has been the most versatile marker of chemical structures, by reflecting global and local electronic structures, and is very sensitive to any change within the chemical species. In this work, Ru(II) complexes with the same five ligands and a variable sixth ligand L (none, H2O, H2S, CH3SH, H2, N2, N2O, NO+, C═CHPh, and CO) are studied by using as the NMR reporter the phosphorus PA of a coordinated bidentate PA-N ligand (PA-N = o-diphenylphosphino-N,N′-dimethylaniline). The chemical shift of PA in RuCl2(PA-N)(PR3)(L) (R = phenyl, p-tolyl, or p-FC6H4) was shown to increase as the Ru–PA bond distance decreases, an observation that was not rationalized. This work, using density functional theory (DFT) calculations, reproduces reasonably well the observed 31P chemical shifts for these complexes and the correlation between the shifts and the Ru–PA bond distance as L varies. An interpretation of this correlation is proposed by using a natural chemical shift (NCS) analysis based on the natural bonding orbital (NBO) method. This analysis of the principal components of the chemical shift tensors shows how the σ-donating properties of L have a particularly high influence on the phosphine chemical shifts.

• Eisenstein, Odile; Ujaque, Gregori & Lledos, Agusti (2020). What Makes a Good (Computed) Energy Profile? In Lledos, Agusti & Ujaque, Gregori (Ed.), New Directions in the Modeling of Organometallic Reactions. Springer. ISSN 9783030569952. p. 1–38. doi: 10.1007/3418_2020_57. Full text in Research Archive Show summary

  A good meal cannot be defined in an absolute manner since it depends strongly on where and how it is eaten and how many people participate. A picnic shared by hikers after a challenging climbing is very different from a birthday party among a family or a banquet for a large convention. All of them can be memorable and also good. The same perspective applies to computational studies. Required level of calculations for spectroscopic properties of small molecular systems and properties of medium or large organic or organometallic, polymetallic systems are different. To well-specified chemical questions and chemical systems, efficient computational strategies can be established. In this chapter, the focus is on the energy profile representation of stoichiometric or catalytic reactions assisted by organometallic molecular entities. The multiple factors that can influence the quality of the calculations of the Gibbs energy profile and thus the mechanistic interpretation of reactions with molecular organometallic complexes are presented and illustrated by examples issued from mostly personal studies. The usual suspects to be discussed are known: representation of molecular models of increasing size, conformational and chemical complexity, methods and levels of calculations, successes and limitations of the density functional methods, thermodynamics corrections, spectator or actor role of the solvent, and static vs dynamics approaches. These well-identified points of concern are illustrated by presentation of computational studies of chemical reactions which are in direct connection with experimental data. Even if problems persist, this chapter aims at illustrating that one can reach a representation of the chemical reality that can be useful to address questions of present chemical interest. Computational chemistry is already well armed to bring meaningful energy information to numerous well-defined questions.

• Peltzer, Raphael Mathias; Gauss, Jürgen; Eisenstein, Odile & Cascella, Michele (2020). The Grignard Reaction − Unraveling a Chemical Puzzle. Journal of the American Chemical Society. ISSN 0002-7863. 142(6), p. 2984–2994. doi: 10.1021/jacs.9b11829. Full text in Research Archive Show summary

  More than 100 years since its discovery, the mechanism of the Grignard reaction remains unresolved. Ambiguities arise from the concomitant presence of multiple organomagnesium species and the competing mechanisms involving either nucleophilic addition or the formation of radical intermediates. To shed light on this topic, quantum-chemical calculations and ab initio molecular dynamics simulations are used to study the reaction of CH3MgCl in tetrahydrofuran with acetaldehyde and fluorenone as prototypical reagents. All organomagnesium species coexisting in solution due to the Schlenk equilibrium are found to be competent reagents for the nucleophilic pathway. The range of activation energies displayed by all of these compounds is relatively small. The most reactive species are a dinuclear Mg complex in which the substrate and the nucleophile initially bind to different Mg centers and the mononuclear dimethyl magnesium. The radical reaction, which requires the homolytic cleavage of the Mg–CH3 bond, cannot occur unless a substrate with a low-lying π*(CO) orbital coordinates the Mg center. This rationalizes why a radical mechanism is detected only in the presence of substrates with a low reduction potential. This feature, in turn, does not necessarily favor the nucleophilic addition, as shown for the reaction with fluorenone. The solvent needs to be considered as a reactant for both the nucleophilic and the radical reactions, and its dynamics is essential for representing the energy profile. The similar reactivity of several species in fast equilibrium implies that the reaction does not occur via a single process but by an ensemble of parallel reactions.

• Gordon, Christopher P.; Culver, Damien B; Conley, Matthew P; Eisenstein, Odile; Andersen, Richard A & Copéret, Christophe (2019). π-Bond Character in Metal–Alkyl Compounds for C–H Activation: How, When, and Why? Journal of the American Chemical Society. ISSN 0002-7863. 141(1), p. 648–656. doi: 10.1021/jacs.8b11951. Full text in Research Archive
• Gordon, Christopher P.; Raynaud, Christophe; Andersen, Richard A; Copéret, Christophe & Eisenstein, Odile (2019). Carbon-13 NMR Chemical Shift: A Descriptor for Electronic Structure and Reactivity of Organometallic Compounds. Accounts of Chemical Research. ISSN 0001-4842. 52(8), p. 2278–2289. doi: 10.1021/acs.accounts.9b00225. Full text in Research Archive
• Eisenstein, Odile (2019). Concluding remarks for “Mechanistic Processes in Organometallic Chemistry”: the importance of a multidisciplinary approach. Faraday discussions. ISSN 1359-6640. 220, p. 489–495. doi: 10.1039/c9fd00101h. Full text in Research Archive
• Suarez, Lluis Artus; Culakova, Zuzana; Balcells, David; Bernskoetter, Wesley H; Eisenstein, Odile & Goldberg, Karen I. [Show all 9 contributors for this article] (2018). The Key Role of the Hemiaminal Intermediate in the Iron-Catalyzed Deaminative Hydrogenation of Amides. ACS Catalysis. 8(9), p. 8751–8762. doi: 10.1021/acscatal.8b02184. Full text in Research Archive
• Gordon, Christopher P.; Yamamoto, Keishi; Searles, Keith; Shirase, Satoru; Andersen, Richard A & Eisenstein, Odile [Show all 7 contributors for this article] (2018). Metal alkyls programmed to generate metal alkylidenes by a-H abstraction: prognosis from NMR chemical shift. Chemical Science. ISSN 2041-6520. 9(7), p. 1912–1918. doi: 10.1039/c7sc05039a. Full text in Research Archive Show summary

  Metal alkylidenes, which are key organometallic intermediates in reactions such as olefination or alkene and alkane metathesis, are typically generated from metal dialkyl compounds [M](CH2R)2 that show distinctively deshielded chemical shifts for their α-carbons. Experimental solid-state NMR measurements combined with DFT/ZORA calculations and a chemical shift tensor analysis reveal that this remarkable deshielding originates from an empty metal d-orbital oriented in the M–Cα–Cα′ plane, interacting with the Cα p-orbital lying in the same plane. This π-type interaction inscribes some alkylidene character into Cα that favors alkylidene generation via α-H abstraction. The extent of the deshielding and the anisotropy of the alkyl chemical shift tensors distinguishes [M](CH2R)2 compounds that form alkylidenes from those that do not, relating the reactivity to molecular orbitals of the respective molecules. The α-carbon chemical shifts and tensor orientations thus predict the reactivity of metal alkyl compounds towards alkylidene generation.

• Gordon, Christopher; Shirase, Satoru; Yamamoto, Keishi; Andersen, Richard A; Eisenstein, Odile & Copéret, Christophe (2018). NMR chemical shift analysis decodes olefin oligo- and polymerization activity of d0 group 4 metal complexes. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 115(26), p. E5867–E5876. doi: 10.1073/pnas.1803382115. Full text in Research Archive Show summary

  0metal-alkyl complexes (M = Ti, Zr, and Hf) show specific activity and selectivity in olefin polymerization and oligomerization depending on their ligand set and charge. Here, we show by a combined experimental and computational study that the13C NMR chemical shift tensors of the α-carbon of metal alkyls that undergo olefin insertion signal the presence of partial alkylidene character in the metal–carbon bond, which facilitates this reaction. The alkylidene character is traced back to the π-donating interaction of a filled orbital on the alkyl group with an empty low-lying metal d-orbital of appropriate symmetry. This molecular orbital picture establishes a connection between olefin insertion into a metal-alkyl bond and olefin metathesis and a close link between the Cossee–Arlmann and Green–Rooney polymerization mechanisms. The13C NMR chemical shifts, the α-H agostic interaction, and the low activation barrier of ethylene insertion are, therefore, the results of the same orbital interactions, thus establishing chemical shift tensors as a descriptor for olefin insertion.

• Gordon, Christopher P.; Yamamoto, Keishi; Liao, Wei-Chih; Allouche, Florian; Andersen, Richard A & Copéret, Christophe [Show all 8 contributors for this article] (2017). Metathesis Activity Encoded in the Metallacyclobutane Carbon-13 NMR Chemical Shift Tensors. ACS Central Science. ISSN 2374-7943. 3(7), p. 759–768. doi: 10.1021/acscentsci.7b00174. Full text in Research Archive Show summary

  Metallacyclobutanes are an important class of organometallic intermediates, due to their role in olefin metathesis. They can have either planar or puckered rings associated with characteristic chemical and physical properties. Metathesis active metallacyclobutanes have short M–Cα/α′ and M···Cβ distances, long Cα/α′–Cβ bond length, and isotropic 13C chemical shifts for both early d0 and late d4 transition metal compounds for the α- and β-carbons appearing at ca. 100 and 0 ppm, respectively. Metallacyclobutanes that do not show metathesis activity have 13C chemical shifts of the α- and β-carbons at typically 40 and 30 ppm, respectively, for d0 systems, with upfield shifts to ca. −30 ppm for the α-carbon of metallacycles with higher dn electron counts (n = 2 and 6). Measurements of the chemical shift tensor by solid-state NMR combined with an orbital (natural chemical shift, NCS) analysis of its principal components (δ11 ≥ δ22 ≥ δ33) with two-component calculations show that the specific chemical shift of metathesis active metallacyclobutanes originates from a low-lying empty orbital lying in the plane of the metallacyclobutane with local π*(M–Cα/α′) character. Thus, in the metathesis active metallacyclobutanes, the α-carbons retain some residual alkylidene character, while their β-carbon is shielded, especially in the direction perpendicular to the ring. Overall, the chemical shift tensors directly provide information on the predictive value about the ability of metallacyclobutanes to be olefin metathesis intermediates.

• Peltzer, Raphael Mathias; Eisenstein, Odile; Nova, Ainara & Cascella, Michele (2017). How Solvent Dynamics Controls the Schlenk Equilibrium of Grignard Reagents: A Computational Study of CH3MgCl in Tetrahydrofuran. Journal of Physical Chemistry B. ISSN 1520-6106. 121(16), p. 4226–4237. doi: 10.1021/acs.jpcb.7b02716. Full text in Research Archive Show summary

  The Schlenk equilibrium is a complex reaction governing the presence of multiple chemical species in solution of Grignard reagents. The full characterization at the molecular level of the transformation of CH3MgCl into MgCl2 and Mg(CH3)2 in tetrahydrofuran (THF) by means of ab initio molecular dynamics simulations with enhanced-sampling metadynamics is presented. The reaction occurs via formation of dinuclear species bridged by chlorine atoms. At room temperature, the different chemical species involved in the reaction accept multiple solvation structures, with two to four THF molecules that can coordinate the Mg atoms. The energy difference between all dinuclear solvated structures is lower than 5 kcal mol–1. The solvent is shown to be a direct key player driving the Schlenk mechanism. In particular, this study illustrates how the most stable symmetrically solvated dinuclear species, (THF)CH3Mg(μ-Cl)2MgCH3(THF) and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF), need to evolve to less stable asymmetrically solvated species, (THF)CH3Mg(μ-Cl)2MgCH3(THF)2 and (THF)CH3Mg(μ-Cl)(μ-CH3)MgCl(THF)2, in order to yield ligand exchange or product dissociation. In addition, the transferred ligands are always departing from an axial position of a pentacoordinated Mg atom. Thus, solvent dynamics is key to successive Mg–Cl and Mg–CH3 bond cleavages because bond breaking occurs at the most solvated Mg atom and the formation of bonds takes place at the least solvated one. The dynamics of the solvent also contributes to keep relatively flat the free energy profile of the Schlenk equilibrium. These results shed light on one of the most used organometallic reagents whose structure in solvent remains experimentally unresolved. These results may also help to develop a more efficient catalyst for reactions involving these species. © 2017 American Chemical Society. This is an ACS AuthorChoice Article.

• Estes, Deven P.; Gordon, Christopher P.; Fedorov, Alexey; Liao, Wei-Chih; Ehrhorn, Henrike & Bittner, Celine [Show all 13 contributors for this article] (2017). Molecular and silica-supported molybdenum aqlkyne metathesis catalysts: influence of electronics and dynamics on activity revealed by kinetics, solid-state NMR, and chemical shift analysis. Journal of the American Chemical Society. ISSN 0002-7863. 139(48), p. 17597–17607. doi: 10.1021/jacs.7b09934. Full text in Research Archive
• Yamamoto, Keishi; Gordon, Christopher P.; Liao, Wei-Chih; Copéret, Christophe; Raynaud, Christophe & Eisenstein, Odile (2017). Orbital Analysis of Carbon-13 Chemical Shift Tensors Reveals Patterns to Distinguish Fischer and Schrock Carbenes. Angewandte Chemie International Edition. ISSN 1433-7851. 56(34), p. 10127–10131. doi: 10.1002/anie.201701537. Full text in Research Archive
• Eisenstein, Odile; Milani, Jessica & Perutz, Robin N. (2017). Selectivity of C-H Activation and Competition between C-H and C-F Bond Activation at Fluorocarbons. Chemical Reviews. ISSN 0009-2665. 117(13), p. 8710–8753. doi: 10.1021/acs.chemrev.7b00163. Full text in Research Archive
• Halbert, Stephanie; Copéret, Christophe; Raynaud, Christophe & Eisenstein, Odile (2016). Elucidating the Link between NMR Chemical Shifts and Electronic Structure in Olefin Metathesis Catalysts. Journal of the American Chemical Society. ISSN 0002-7863. 138(7), p. 2261–2272. doi: 10.1021/jacs.5b12597. Full text in Research Archive
• Balcells, David; Clot, Eric; Eisenstein, Odile; Nova, Ainara & Perrin, Lionel (2016). Deciphering Selectivity in Organic Reactions: A Multifaceted Problem. Accounts of Chemical Research. ISSN 0001-4842. 49(5), p. 1070–1078. doi: 10.1021/acs.accounts.6b00099. Full text in Research Archive
• Balcells, David; Eisenstein, Odile; Tilset, Mats & Nova, Ainara (2016). Coordination and insertion of alkenes and alkynes in AuIII complexes: nature of the intermediates from a computational perspective. Dalton Transactions. ISSN 1477-9226. 45(13), p. 5504–5513. doi: 10.1039/c5dt05014f. Full text in Research Archive
• Aasheim, Jens Harald; Fliegl, Heike; Uggerud, Einar; Bonge-Hansen, Tore & Eisenstein, Odile (2014). Stereoselectivity through a network of non-classical CH weak interactions: A prospective study of a bicyclic organocatalytic scaffold. New Journal of Chemistry. ISSN 1144-0546. 38(12), p. 5975–5982. doi: 10.1039/c4nj01460j. Full text in Research Archive
• Nova, Ainara; Suh, Hee-Won; Schmeier, Timothy J.; Guard, Louise M.; Eisenstein, Odile & Hazari, Nilay [Show all 7 contributors for this article] (2014). An unusual example of hypervalent silicon: a five-coordinate silyl group bridging two palladium or nickel centers through a nonsymmetrical four-center two-electron bond. Angewandte Chemie International Edition. ISSN 1433-7851. 53(4), p. 1103–1108. doi: 10.1002/anie.201307618. Full text in Research Archive
• Nova, Ainara; Taylor, David; Blacker, A. John; Duckett, Simon B.; Perutz, Robin N. & Eisenstein, Odile (2014). Computational studies explain the importance of two different substituents on the chelating bis(amido) ligand for transfer hydrogenation by bifunctional Cp*Rh(III) catalysts. Organometallics. ISSN 0276-7333. 33(13), p. 3433–3442. doi: 10.1021/om500356e. Full text in Research Archive
• Hennum, Martin; Fliegl, Heike; Gundersen, Lise-Lotte & Eisenstein, Odile (2014). Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl imines. Journal of Organic Chemistry. ISSN 0022-3263. 79(6), p. 2514–2521. doi: 10.1021/jo402802j. Full text in Research Archive Show summary

  The asymmetric nucleophilic 1,2-addition of (S)-N-benzylidene-2-methylpropane-2-sulfinamide with methylmagnesium bromide and methyllithium has been investigated using DFT(B3LYP) computations. The calculated ratio of the two diastereomers agrees with experimental observations and the factors that determine the diastereomeric ratio are discussed. The preference for the E isomer and the rapid equilibrium between the E and Z isomers of N-tert-butanesulfinyl imine are two key features for understanding the mechanism of this reaction. Methylmagnesium bromide and methyllithium have bifunctional roles, acting as both Lewis acid and nucleophile and the Lewis acid character has a determining role on the stereoselectivity of the reaction.

• Møllendal, Harald; Balcells, David; Eisenstein, Odile; Syversen, Linda & Suissa, Michal Rachel (2014). Conformational Complexity of Morphine and Morphinum in the Gas Phase and in Water. A DFT and MP2 Study. RSC Advances. 4(47), p. 24729–24735. doi: 10.1039/c4ra02992e. Full text in Research Archive Show summary

  The structural and conformational properties of morphine and protonated morphine (morphinum) in the gas phase and in water solution have been explored with quantum calculations. Fully optimized calculations using the cc-pVTZ basis set, with various methods (MP2, B3LYP, and PBE0) for the species in the gas phase and with B3LYP with simulation of the solvent effect as a continuum with the SMD method were conducted. The study focuses on the determination of the relative energies of the 12 possible conformers that arise from the orientation of the two OH groups and the equatorial vs axial position of the methyl group on the nitrogen and the energy barriers that separate these minima. The calculations indicate a preference for conformers having the methyl group equatorial, but corresponding axial conformers are not significantly higher in energy. Only 8 of the 12 possible conformers of gaseous morphine were found to be minima on the potential energy hypersurface. All 12 conformers of morphinum are minima according to MP2 computations. B3LYP/SMD (water) calculations predict the coexistence of 12 conformers for both morphine and morphinum with energy ranges of 17 kJ/mol for morphine, and as low as 13 kJ/mol for morphinum. In morphinum, energy differences less than 8 kJ/mol are computed for 8 conformers, including axial forms. The inversion at nitrogen is calculated to be energetically accessible at room temperature since the activation barrier is less than 30 kJ/mol in gas phase and only around 40 kJ/mol with simulated water solvation. The many conformers within a small energy span, the fact that a thermodynamic equilibrium exists between morphine and morphinum in water, and the rapid nitrogen inversion show that morphine and morphinum have a large conformational diversity in water, and thus in the physiological media, which could be a clue to the interaction of this drug with receptors.

• Langseth, Eirin; Scheuermann, Margaret L.; Balcells, David; Kaminsky, Werner; Goldberg, Karen I. & Eisenstein, Odile [Show all 8 contributors for this article] (2013). Generation and Structural Characterization of a Gold(III) Alkene Complex. Angewandte Chemie International Edition. ISSN 1433-7851. 52, p. 1660–1660. Full text in Research Archive
• Langseth, Eirin; Scheuermann, Margaret Louise; Balcells, David; Kaminsky, Werner; Goldberg, Karen I. & Eisenstein, Odile [Show all 8 contributors for this article] (2013). Generation and Structural Characterization of a Gold(III) Alkene Complex. Angewandte Chemie International Edition. ISSN 1433-7851. 52(6), p. 1660–1663. doi: 10.1002/anie.201209140. Full text in Research Archive Show summary

  A Missing Gold Link: An AuIII alkene complex has been prepared and characterized by NMR spectroscopy and X-ray crystallography. Its bonding features have been analyzed by DFT calculations and natural bond orbital (NBO) analysis. In [(cod)AuMe2]+, the unequal AuC bond lengths result from the domination of the preference of 1,5-cyclooctadiene (cod) for nonparallel double bonds over back donation from the metal which favors parallel double bonds.

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• Eisenstein, Odile; Cascella, Michele & Pradier, Claire-Marie (2021). La reaction de Grignard, une enigme de 120 ans chapter in Etonnante Chimie Decouvertes et promesses du XXIeme siècle. CNRS Editions. ISBN 9782271136527. 340 p. Full text in Research Archive

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• Eliasson, Sondre Hilmar Hopen; Giovanetti, Marinella de; Bore, Sigbjørn Løland; Cascella, Michele & Eisenstein, Odile (2024). Machine Learned Potential for Organolithium Compounds in THF. Full text in Research Archive
• Eliasson, Sondre Hilmar Hopen; Giovanetti, Marinella de; Bore, Sigbjørn Løland; Cascella, Michele & Eisenstein, Odile (2024). Machine Learned Potential for Organolithium Compounds in THF. Full text in Research Archive
• Cascella, Michele; Eisenstein, Odile & Herzberg, Nathaniel (2024). Le gang des Grignard démasqué. [Journal]. Le Monde . Full text in Research Archive
• Eliasson, Sondre Hilmar Hopen; Giovanetti, Marinella de; Bore, Sigbjørn Løland; Bortoli, Marco; Cascella, Michele & Eisenstein, Odile (2023). Machine Learned Potential for Organolithium in THF. Full text in Research Archive
• Eisenstein, Odile & Shaik, Sason (2022). Computational Catalysis: A Land of Opportunities. Topics in catalysis. ISSN 1022-5528. 65, p. 1–5. doi: 10.1007/s11244-021-01555-5. Full text in Research Archive
• Eisenstein, Odile (2021). Le peintre un chimiste qui s’ignore. Full text in Research Archive
• Eisenstein, Odile & Raynaud, christophe (2021). Computational analysis of NMR chemical shift: Relationship to bonding. Full text in Research Archive
• Eisenstein, Odile (2021). Bob Crabtree and I From the South West of Paris to ... Full text in Research Archive
• Eisenstein, Odile (2021). L'énigme Grignard une affaire classée... ou pas ? Full text in Research Archive
• Eisenstein, Odile & Cascella, Michele (2021). Grignard reagent and Grignard reaction: Computational approach of a chemical puzzle. Full text in Research Archive
• Eisenstein, Odile (2021). What can solid-state NMR tell about chemical bonds? Full text in Research Archive
• Gordon, Christopher; Raynaud, Christophe; Copéret, Christophe & Eisenstein, Odile (2021). What can solid-state NMR tell about chemical bonds? Full text in Research Archive
• Eisenstein, Odile (2020). Solvent role on organometallic reactions. Full text in Research Archive
• Eisenstein, Odile (2019). Anisotropy of Solid State NMR Chemical Shift Signal and the Analysis of the Metal Alkyl Bond in d0 Metal Alkyl Complexes. Full text in Research Archive
• Eisenstein, Odile (2019). Challenging computational chemistry with chemical questions. Full text in Research Archive
• Eisenstein, Odile (2019). Art and Chemistry, Chemistry and Art. Full text in Research Archive
• Eisenstein, Odile (2019). Some insight in the mechanism of the Grignard reaction. Full text in Research Archive
• Eisenstein, Odile (2019). Computations trying to catch up with experiments. Full text in Research Archive
• Eisenstein, Odile; Raynaud, Christophe; Coperet, Christophe; Andersen, Richard A & Gordon, Christopher (2019). To have and have not: the NMR signature of metal-C p bond. Full text in Research Archive
• Eisenstein, Odile (2019). Information about reactivity from NMR? An approach combining solid state NMR and quantum calculations. Full text in Research Archive
• Eisenstein, Odile; Raynaud, Christophe & Coperet, Christophe (2019). Anisotropy of solid state NMR Chemical Shift signal informs on the π character of M-alkyl σ-bond in d0metal alkyl complexes. Full text in Research Archive
• Eisenstein, Odile (2019). « Quantum based » Computational chemistry: An interpret for structures and properties during chemical reaction. Full text in Research Archive
• Eisenstein, Odile (2019). The 13C Solid State NMR Signature of Metal-bonded Carbon: An information of Bonding and Reactivity. Full text in Research Archive
• Eisenstein, Odile (2019). Reactivity in organometallic complexes from Dynamic and solid-state NMR. Full text in Research Archive
• Eisenstein, Odile (2018). Chemistry: the Color of Universe. Full text in Research Archive
• Eisenstein, Odile (2018). Information about reactivity from NMR? An approach combining solid state NMR and quantum calculations. Full text in Research Archive
• Eisenstein, Odile (2018). Analyzing reaction pathway Is there an alternative to energy? Full text in Research Archive
• Eisenstein, Odile; Raynaud, Christophe & Coperet, Christophe (2018). Information about reactivity from NMR? An approach combining solid state NMR and quantum calculations. Full text in Research Archive
• Eisenstein, Odile (2018). Information about reactivity from NMR? An approach combining solid state NMR and quantum calculations. Full text in Research Archive
• Eisenstein, Odile (2018). The adventures of a computational chemist among chemists. Full text in Research Archive
• Eisenstein, Odile (2018). Information about reactivity from NMR? An approach combining solid state NMR and quantum calculations. Full text in Research Archive
• Eisenstein, Odile (2018). Analyzing reaction pathway: is there an alternative to energy ? Full text in Research Archive
• Mennucci, Benedetta; Eisenstein, Odile; Fliegl, Heike; Hopmann, Kathrin Helen; Helgaker, Trygve & Ruud, Kenneth (2015). FemEx—Female Excellence in Theoretical and Computational Chemistry. International Journal of Quantum Chemistry. ISSN 0020-7608. doi: 10.1002/qua.24961. Full text in Research Archive
• Hennum, Martin; Fliegl, Heike; Gundersen, Lise-Lotte & Eisenstein, Odile (2014). Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl imines. Full text in Research Archive
• Møllendal, Harald; Balcells, David; Eisenstein, Odile & Suissa, Michal Rachel (2014). Conformational analysis and theoretical calculations of morphine and morphinum, in the gas phase and in water: A DFT and MP2 study. Full text in Research Archive
• Hennum, Martin; Eisenstein, Odile; Fliegl, Heike & Gundersen, Lise-Lotte (2013). Mechanistic insights on the stereoselective nucleophilic 1,2-addition to sulfinyl imines. Full text in Research Archive
• Langseth, Eirin; Scheuermann, Margaret Louise; Balcells, David; Kaminsky, Werner; Goldberg, Karen I. & Eisenstein, Odile [Show all 8 contributors for this article] (2013). Cyclometalated Gold(III) Complexes and a Gold(III) Alkene Complex. Full text in Research Archive
• Langseth, Eirin; Scheuermann, Margaret Louise; Balcells, David; Kaminsky, Werner; Goldberg, Karen I. & Eisenstein, Odile [Show all 8 contributors for this article] (2013). Generation and structural characterization of a gold(III) alkene complex. Full text in Research Archive

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