New Directions in the Modeling of Organometallic Reactions

Table of Contents

1. Frontmatter

2. What Makes a Good (Computed) Energy Profile?

   Odile Eisenstein, Gregori Ujaque, Agustí Lledós

   Abstract

   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.

3. Mechanisms of Metal-Catalyzed Electrophilic F/CF3/SCF3 Transfer Reactions from Quantum Chemical Calculations

   Binh Khanh Mai, Fahmi Himo

   Abstract

   Electrophilic F/CF₃/SCF₃ transfer reactions have recently emerged as a promising strategy to introduce fluorine substituents to organic compounds at mild conditions with high reactivity and selectivity. Several safe and stable electrophilic reagents have been introduced and have found interesting applications in synthetic chemistry. To control the reactivity and selectivity of these reactions, metal catalysts are typically used in combination with the reagents. Herein, we describe our recent efforts to elucidate the detailed mechanisms and origins of selectivity for a number of metal-catalyzed electrophilic F/CF₃/SCF₃ transfer reactions using density functional theory calculations. Focus is on reactions employing hypervalent fluoroiodine and nitrogen-based reagents, with zinc or rhodium as the metal catalysts. The roles of the metal ions are discussed, and some novel mechanistic ideas have emerged from these calculations that can have bearing on other reactions for introducing fluorine-containing groups.

4. Artificial Force-Induced Reaction Method for Systematic Elucidation of Mechanism and Selectivity in Organometallic Reactions

   Miho Hatanaka, Takayoshi Yoshimura, Satoshi Maeda

   Abstract

   The computational methods to find the transition states (TSs) are powerful to understand the mechanisms of organometallic reactions. Recently, automatic and systematic search methods of reaction pathways have attracted attention. Among them, one of the most successful methods is the artificial force-induced reaction (AFIR) method. The advantage of the AFIR method is that the reaction pathways can be explored without the prejudgment of the products as well as the reaction coordinates. In this chapter, the concept and algorithms of the AFIR method are described. We also introduce the recent AFIR studies about organometallic reactions and show how the exhaustively gathered TSs contribute to a better understanding of the reaction mechanism and the origin of the selectivity.

5. DFT-Based Microkinetic Simulations: A Bridge Between Experiment and Theory in Synthetic Chemistry

   Martín Jaraíz

   Abstract

   The goal of this chapter is to enable the reader to carry out microkinetic modeling and simulation studies of synthetic chemistry problems, assuming the availability of a set of DFT energy values for the reaction rates involved. To this end, after a brief introduction, we describe the tools that we use and the modeling methodology that we follow and then provide a short tutorial and input files for the microkinetic simulator that we normally use (available free of charge). Finally, we analyze two case examples to show the remarkable level of insight and prediction power attainable with this DFT-based microkinetic modeling methodology.

6. A Quantitative Approach to Understanding Reactivity in Organometallic Chemistry

   Israel Fernández

   Abstract

   This chapter presents the combination of the activation strain model (ASM) of reactivity and the energy decomposition analysis (EDA) methods as an alternative approach to gain quantitative insight into the reactivity trends in organometallic chemistry. Besides a brief presentation of the basics of these quantum chemical methods, representative recent applications of this approach to fundamental transition metal (TM)-mediated reactions are discussed. The selected transformations span from typical oxidative addition or β-elimination processes to more intricate gold (I)-mediated hydroarylation or hydroamination reactions, therefore covering a good number of different processes in organometallic chemistry. The contents of this chapter show not only the good performance of this computational methodology to understand the physical factors controlling the reactivity in organometallic chemistry but also its usefulness toward the rational design of more efficient transformations.

7. Computational Modeling of Selected Photoactivated Processes

   Adiran de Aguirre, Victor M. Fernandez-Alvarez, Feliu Maseras

   Abstract

   Photoactivated processes play an increasingly important role in chemistry. Their widespread use is still relatively recent, and the application of computational methods to the treatment of the large systems usually involved in experimentally relevant systems is even more recent. The application of TD-DFT calculations for the photoactivation step and of conventional DFT calculations for selected regions of the potential energy surface has been demonstrated as a powerful tool for mechanistic understanding. This contribution presents four representative examples of this application, highlighting the successes and the struggles of this type of treatments.

8. Ligand Design for Asymmetric Catalysis: Combining Mechanistic and Chemoinformatics Approaches

   Ruchuta Ardkhean, Stephen P. Fletcher, Robert S. Paton

   Abstract

   A core element to the successful development of asymmetric catalytic reactions is finding a suitable chiral catalyst or ligand. The discovery and optimization of chiral catalysts can be enormously challenging. Traditionally, chemists have approached this endeavour by screening existing ligands. The most promising structures are then modified based on mechanistic knowledge, chemical intuition and the results of screening experiments, with the aim of optimizing selectivity and yield. However, this empirical approach has begun to change: new methods to accelerate the experimental screening process have emerged together with computational and physical-organic approaches that provide a systematic, and hopefully faster, route to new catalysts. Practical and theoretical understanding of high-throughput screening and multi-parameter optimization are now requirements at the cutting edge of the field, in addition to synthetic and mechanistic expertise.

   In this chapter, we summarize the recent examples of combinatorial approaches taken to discover and develop asymmetric catalytic transformations. In particular, we highlight the use of quantitative models to predict reaction outcomes. A series of guidelines are presented to aid chemists in adopting these approaches, followed by illustrated examples of recent work in this area.

9. Dealing with Spin States in Computational Organometallic Catalysis

   Marcel Swart

   Abstract

   The present chapter gives an overview of the intriguing effects that spin states have on catalysis and how this can (and cannot) be understood at present. For instance, highly reactive transition-metal complexes are often too fast to be trapped for characterization by spectroscopy and/or crystallography. While significant advances have been made in theory with improved density functional approximations and more efficient wavefunction methods, these have not yet progressed to the point of being robust general-purpose chemical tools. Recent developments in the application of spectroscopy and theory on catalytically (in)active transition-metal complexes are discussed together with future perspectives.

10. Characterizing the Metal–Ligand Bond Strength via Vibrational Spectroscopy: The Metal–Ligand Electronic Parameter (MLEP)

    Elfi Kraka, Marek Freindorf

    Abstract

    The field of organometallic chemistry has tremendously grown over the past decades and become an integral part of many areas of chemistry and beyond. Organometallic compounds find a wide use in synthesis, where organometallic compounds are utilized as homogeneous/heterogeneous catalysts or as stoichiometric reagents. In particular, modifying and fine-tuning organometallic catalysts has been at the focus. This requires an in-depth understanding of the complex metal–ligand (ML) interactions which are playing a key role in determining the diverse properties and rich chemistry of organometallic compounds. We introduce in this article the metal–ligand electronic parameter (MLEP), which is based on the local vibrational ML stretching force constant, fully reflecting the intrinsic strength of this bond. We discuss how local vibrational stretching force constants and other local vibrational properties can be derived from the normal vibrational modes, which are generally delocalized because of mode–mode coupling, via a conversion into local vibrational modes, first introduced by Konkoli and Cremer. The MLEP is ideally suited to set up a scale of bond strength orders, which identifies ML bonds with promising catalytic or other activities. The MLEP fully replaces the Tolman electronic parameter (TEP), an indirect measure, which is based on the normal vibrational CO stretching frequencies of [R_nM(CO)_mL] complexes and which has been used so far in hundreds of investigations. We show that the TEP is at best a qualitative parameter that may fail. Of course, when it was introduced by Tolman in the 1960s, one could not measure the low-frequency ML vibration directly, and our local mode concept did not exist. However, with these two problems solved, a new area of directly characterizing the ML bond has begun, which will open new avenues for enriching organometallic chemistry and beyond.