Giovanni Occhipinti

Metal−Phosphine Bond Strengths of the Transition Metals: A Challenge for DFT†

Previous promising tests of the new M06 family of functionals in predicting ruthenium-metal phosphine bond dissociation energies (Zhao, Y.; Truhlar, D. G. Acc. Chem. Res. 2008, 41, 157) have been extended to a series of phosphine complexes of chromium, molybdenum, nickel, and ruthenium for which relevant experimental data are available. In addition to the M06 family of functionals, bond dissociation enthalpies have been calculated using a selection of density functionals and hybrid functionals based on the generalized gradient approximation (GGA), and with or without an empirical term (i.e., DFT-D) accounting for long-range dispersion. For the ruthenium complexes, second-order Møller-Plesset perturbation theory (MP2) has also been applied. Electrostatic and nonelectrostatic solvent effects have been estimated using the polarizable continuum model (PCM), allowing for comparison with experimental data obtained for dissociation reactions in organic solvents. Whereas the GGA and hybrid-GGA functionals grossly underestimate the absolute metal-phosphine bond enthalpies, with mean unsigned errors (MUEs) for a set of 10 phosphine dissociation reactions in the range 13-27 kcal/mol, the recently developed DFT-based methods for inclusion of attractive noncovalent interactions and dispersion (the DFT-D and M06 functionals) dramatically improve upon the situation. The best agreement with experiment is observed for BLYP-D (MUE = 2.2 kcal/mol), and with the exception for M06-2X, all these methods provide MUEs well below 5 kcal/mol, which should be sufficient for a broad range of applications. The improvements in predicted relative bond enthalpies are less convincing, however. In several cases the GGA and hybrid-GGA functionals are better at reproducing substitution effects than the DFT-D and M06 methods.

Simple and Highly Z-Selective Ruthenium-Based Olefin Metathesis Catalyst

A one-step substitution of a single chloride anion of the Grubbs-Hoveyda second-generation catalyst with a 2,4,6-triphenylbenzenethiolate ligand resulted in an active olefin metathesis catalyst with remarkable Z selectivity, reaching 96% in metathesis homocoupling of terminal olefins. High turnover numbers (up to 2000 for homocoupling of 1-octene) were obtained along with sustained appreciable Z selectivity (>85%). Apart from the Z selectivity, many properties of the new catalyst, such as robustness toward oxygen and water as well as a tendency to isomerize substrates and react with internal olefin products, resemble those of the parent catalyst.

Synthesis and Stability of Homoleptic Metal(III) Tetramethylaluminates

Whereas a number of homoleptic metal(III) tetramethylaluminates M(AlMe(4))(3) of the rare earth metals have proven accessible, the stability of these compounds varies strongly among the metals, with some even escaping preparation altogether. The differences in stability may seem puzzling given that this class of metals usually is considered to be relatively uniform with respect to properties. On the basis of quantum chemically obtained relative energies and atomic and molecular descriptors of homoleptic tris(tetramethylaluminate) and related compounds of rare earth metals, transition metals, p-block metals, and actinides, multivariate modeling has identified the importance of ionic metal-methylaluminate bonding and small steric repulsion between the methylaluminate ligands for obtaining stable homoleptic compounds. Low electronegativity and a sufficiently large ionic radius are thus essential properties for the central metal atom. Whereas scandium and many transition metals are too small and too electronegative for this task, all lanthanides and actinides covered in this study are predicted to give homoleptic compounds stable toward loss of trimethylaluminum, the expected main decomposition reaction. Three of the predicted lanthanide-based compounds Ln(AlMe(4))(3) (Ln = Ce, Tm, Yb) have been prepared and fully characterized in the present work, in addition to Ln(OCH(2)tBu)(3)(AlMe(3))(3) (Ln = Sc, Nd) and [Eu(AlEt(4))(2)](n). At ambient temperature, donor-free hexane solutions of Ln(AlMe(4))(3) of the Ln(3+)/Ln(2+) redox-active metal centers display enhanced reduction to [Ln(AlMe(4))(2)](n) with decreasing negative redox potential, in the order Eu ≫ Yb ≫ Sm. Whereas Eu(AlMe(4))(3) could not be identified, Yb(AlMe(4))(3) turned out to be isolable in low yield. All attempts to prepare the putative Sc(AlMe(4))(3), featuring the smallest rare earth metal center, failed.

An evolutionary algorithm for de novo optimization of functional transition metal compounds.

Development of functional inorganic and transition metal compounds is usually based on ad hoc qualified guesses, with computational methods playing a lesser role than in drug discovery. A de novo evolutionary algorithm (EA) is presented that automatically generates transition metal complexes using a search space constrained around chemically meaningful structures assembled from three kinds of fragments: a part shared by all structures and typically containing the metal center itself, one or several parts consisting of ligand skeletons, and unconstrained parts that may grow and vary freely. In EA optimizations, using a cost-efficient fitness function based on a linear quantitative structure-activity relationship model for catalytic activity, we demonstrate the capabilities of the method by retracing the transition from the first-generation, phosphine-based Grubbs olefin metathesis catalysts to second-generation catalysts containing N-heterocyclic carbene ligands instead of phosphines. Moreover, DFT calculations on selected high-fitness, last-generation structures from these evolutionary experiments suggest that, in terms of catalytic activity, the structures arrived at by virtual evolution alone compare favorably with existing, highly active catalysts. The structures from the evolution experiments are, however, complex and probably difficult to synthesize, but a set of manually simplified variations thereof might form the leads for a new generation of Grubbs catalysts.

Automated design of realistic organometallic molecules from fragments.

A method for the automated generation of realistic, synthetically accessible transition metal and organometallic complexes is described. Computational tools were designed to generate molecular fragments, preferably harvested from libraries of existing, stable compounds, to be used as building blocks for the construction of new molecules. These fragments are enriched with information about the number and type of possible connections to other fragments and are stored in library files. When connecting fragments in the subsequent building process, compatibility matrices, which define the connection rules between fragments, are used to delineate organometallic fragment spaces from which molecules can be generated in an automated fashion. The approach is flexible and allows ample structural variation at the same time as the combination of known fragments is easily restrained to avoid generation of exotic and unrealistic substructures and molecules. The method was tested in the generation of ruthenium complexes, with a given coordination environment, which can serve as candidates in catalyst development. The results demonstrate that molecules generated with the described method do not contain exotic arrangements of atoms and are by far more realistic than those obtained by the application of valence rules alone.

Neutral Nickel Oligo‐ and Polymerization Catalysts: The Importance of Alkyl Phosphine Intermediates in Chain Termination

An unconventional chain termination reaction has been explored for the SHOP (Shell higher olefin process)-type, anilinotropone, and salicylaldiminato nickel-based oligo- and polymerization catalysts by using density functional theory (DFT). Starting from the tetracoordinate alkyl phosphine complex, the termination reaction was found to involve a rearrangement of the alkyl chain to form a pentacoordinate β-agostic complex, β-hydride elimination, and olefinic chain dissociation and to compete with propagation at sufficiently high phosphine concentration and/or basicity. It provides the first complete and convincing mechanistic rationale for the decreasing chain lengths observed upon increasing phosphine concentration and basicity. The unconventional reaction was found to be a major termination pathway for the SHOP-type catalyst and is very unlikely to lead to branching and olefin isomerization, which is critical for explaining why the SHOP catalyst, in contrast to the anilinotropone and salicylaldiminato catalysts, tends to lead to the oligomerization of ethylene to form linear α-olefins. Based on our results we have proposed a new and extended catalytic cycle for the SHOP-type ethylene oligomerization catalyst. Finally, the importance of the new termination reaction for the SHOP-type catalyst suggests that this reaction may also operate with other ethylene oligomerization nickel catalysts. This prediction was confirmed for a pyrazolonatophosphine catalyst, for which the new termination route was found to be even more facile, which explains the short oligomers produced by this catalyst.

Neutral Nickel Ethylene Oligo‐ and Polymerization Catalysts: Towards Computational Catalyst Prediction and Design

DFT calculations have been used to elucidate the chain termination mechanisms for neutral nickel ethylene oligo- and polymerization catalysts and to rationalize the kind of oligomers and polymers produced by each catalyst. The catalysts studied are the (κ(2)-O,O)-coordinated (1,1,1,5,5,5-hexafluoro-2,4-acetylacetonato)nickel catalyst I, the (κ(2)-P,O)-coordinated SHOP-type nickel catalyst II, the (κ(2)-N,O)-coordinated anilinotropone and salicylaldiminato nickel catalysts III and IV, respectively, and the (κ(2)-P,N)-coordinated phosphinosulfonamide nickel catalyst V. Numerous termination pathways involving β-H elimination and β-H transfer steps have been investigated, and the most probable routes identified. Despite the complexity and multitude of the possible termination pathways, the information most critical to chain termination is contained in only few transition states. In addition, by consideration of the propagation pathway, we have been able to estimate chain lengths and discriminate between oligo- and polymerization catalysts. In agreement with experiment, we found the Gibbs free energy difference between the overall barrier for the most facile propagation and termination pathways to be close to 0 kcal mol(-1) for the ethylene oligomerization catalysts I and V, whereas values of at least 7 kcal mol(-1) in favor of propagation were determined for the polymerization catalysts III and IV. Because of the shared intermediates between the termination and branching pathways, we have been able to identify the preferred cis/trans regiochemistry of β-H elimination and show that a pronounced difference in σ donation of the two bridgehead atoms of the bidentate ligand can suppress hydride formation and thus branching. The degree of rationalization obtained here from a handful of key intermediates and transition states is promising for the use of computational methods in the screening and prediction of new catalysts of the title class.

Automated Building of Organometallic Complexes from 3D Fragments

A method for the automated construction of three-dimensional (3D) molecular models of organometallic species in design studies is described. Molecular structure fragments derived from crystallographic structures and accurate molecular-level calculations are used as 3D building blocks in the construction of multiple molecular models of analogous compounds. The method allows for precise control of stereochemistry and geometrical features that may otherwise be very challenging, or even impossible, to achieve with commonly available generators of 3D chemical structures. The new method was tested in the construction of three sets of active or metastable organometallic species of catalytic reactions in the homogeneous phase. The performance of the method was compared with those of commonly available methods for automated generation of 3D models, demonstrating higher accuracy of the prepared 3D models in general, and, in particular, a much wider range with respect to the kind of chemical structures that can be built automatically, with capabilities far beyond standard organic and main-group chemistry.

Loss and Reformation of Ruthenium Alkylidene: Connecting Olefin Metathesis, Catalyst Deactivation, Regeneration, and Isomerization

Ruthenium-based olefin metathesis catalysts are used in laboratory-scale organic synthesis across chemistry, largely thanks to their ease of handling and functional group tolerance. In spite of this robustness, these catalysts readily decompose, via little-understood pathways, to species that promote double-bond migration (isomerization) in both the 1-alkene reagents and the internal-alkene products. We have studied, using density functional theory (DFT), the reactivity of the Hoveyda-Grubbs second-generation catalyst 2 with allylbenzene, and discovered a facile new decomposition pathway. In this pathway, the alkylidene ligand is lost, via ring expansion of the metallacyclobutane intermediate, leading to the spin-triplet 12-electron complex (SIMes)RuCl2 (3R21, SIMes = 1,3-bis(2,4,6-trimethylphenyl)-4,5-dihydroimidazol-2-ylidene). DFT calculations predict 3R21 to be a very active alkene isomerization initiator, either operating as a catalyst itself, via a η3-allyl mechanism, or, after spin inversion to give R21 and formation of a cyclometalated Ru-hydride complex, via a hydride mechanism. The calculations also suggest that the alkylidene-free ruthenium complexes may regenerate alkylidene via dinuclear ruthenium activation of alkene. The predicted capacity to initiate isomerization is confirmed in catalytic tests using p-cymene-stabilized R21 (5), which promotes isomerization in particular under conditions favoring dissociation of p-cymene and disfavoring formation of aggregates of 5. The same qualitative trends in the relative metathesis and isomerization selectivities are observed in identical tests of 2, indicating that 5 and 2 share the same catalytic cycles for both metathesis and isomerization, consistent with the calculated reaction network covering metathesis, alkylidene loss, isomerization, and alkylidene regeneration.

Decomposition of Olefin Metathesis Catalysts by Brønsted Base: Metallacyclobutane Deprotonation as a Primary Deactivating Event

Brønsted bases of widely varying strength are shown to decompose the metathesis-active Ru intermediates formed by the second-generation Hoveyda and Grubbs catalysts. Major products, in addition to propenes, are base·HCl and olefin-bound, cyclometalated dimers [RuCl(κ2-H2IMes-H)(H2C═CHR)]2 Ru-3. These are generated in ca. 90% yield on metathesis of methyl acrylate, styrene, or ethylene in the presence of either DBU, or enolates formed by nucleophilic attack of PCy3 on methyl acrylate. They also form, in lower proportions, on metathesis in the presence of the weaker base NEt3. Labeling studies reveal that the initial site of catalyst deprotonation is not the H2IMes ligand, as the cyclometalated structure of Ru-3 might suggest, but the metallacyclobutane (MCB) ring. Computational analysis supports the unexpected acidity of the MCB protons, even for the unsubstituted ring, and by implication, its overlooked role in decomposition of Ru metathesis catalysts.