Reliable and efficient reaction path and transition state finding for surface reactions with the growing string method

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136310/1/jcc24720_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136310/2/jcc24720.pd

An unexpected Ireland–Claisen rearrangement cascade during the synthesis of the tricyclic core of Curcusone C: Mechanistic elucidation by trial-and-error and automatic artificial force-induced reaction (AFIR) computations

In the course of a total synthesis effort directed toward the natural product curcusone C, the Stoltz group discovered an unexpected thermal rearrangement of a divinylcyclopropane to the product of a formal Cope/1,3-sigmatropic shift sequence. Since the involvement of a thermally forbidden 1,3-shift seemed unlikely, theoretical studies involving two approaches, the “trial-and-error” testing of various conceivable mechanisms (Houk group) and an “automatic” approach using the Maeda–Morokuma AFIR method (Morokuma group) were applied to explore the mechanism. Eventually, both approaches converged on a cascade mechanism shown to have some partial literature precedent: Cope rearrangement/1,5-sigmatropic silyl shift/Claisen rearrangement/retro-Claisen rearrangement/1,5-sigmatropic silyl shift, comprising a quintet of five sequential thermally allowed pericyclic rearrangements

Exploration of Reaction Pathways and Chemical Transformation Networks

For the investigation of chemical reaction networks, the identification of all relevant intermediates and elementary reactions is mandatory. Many algorithmic approaches exist that perform explorations efficiently and automatedly. These approaches differ in their application range, the level of completeness of the exploration, as well as the amount of heuristics and human intervention required. Here, we describe and compare the different approaches based on these criteria. Future directions leveraging the strengths of chemical heuristics, human interaction, and physical rigor are discussed.Comment: 48 pages, 4 figure

Development of Reaction Discovery Tools in Photochemistry and Condensed Phases

Photochemistry obeys different rules than ground-state chemistry and by doing so opens avenues for synthesis and materials properties. However, the different rules of photochemistry make understanding the fine details of photochemical reactions difficult. Computational chemistry can provide the details for understanding photochemical reactions, but the field of computational photochemistry is still new, and many techniques developed for ground-state reactions are not directly applicable to photochemical reactions. As a result, many photochemical mechanisms are not understood, and this hinders the rational design and synthesis of new photochemistry. To address this need, this thesis develops techniques to search for and study photochemical reactions. Chapter 2 and 3 develop methods to calculate photochemical reactions in gas- and condensed-phases via minimum energy reaction paths. First, Chapter 2 develops a method to search the molecular 3N-6 space for photochemical reactions. This space, although vast, is not chaotic and can be efficiently searched using a concept familiar to chemists: breaking and adding bonds and driving angles and torsions. Furthermore, this procedure can be automated to predict new chemistry not previously identified by experiments. Chapter 3 furthers this research by leveraging the concept of molecules to enable the computational study of reactions in large multi-molecular systems like crystals. Specifically, the use of a new coordinate system involving translational and rotational coordinates allows decoupling of the coordinate systems of the individual molecules, which is necessary for the efficient algebra. Importantly, these methods are general, they can be used to study single molecules and crystals, and much in between. These methods are demonstrated on complex chemical problems including the isomerization pathways of ethylene and stilbene (Chapter 2), the photocycloaddition of butadiene (Chapter 2), the rotation of a crystalline gyroscope (Chapter 3), the bicycle pedal rotation of cis,cis-diphenylbutadiene (Chapter 4), and the mechanism of a reversible photoacid (Chapter 5). These problems have value in understanding the processes of vision, optomechanics, and high-energy materials, and through their xx study much needed insight is gained that can be useful for designing new syntheses and materials. Furthermore, the new computational methods open the possibility for many future investigations. The results of Chapter 2 find a novel roaming-atom and hula-twist isomerization pathway and use automated reaction discovery tools to identify a missing butadiene photoproduct and why the [4+2] cycloaddition is forbidden. The results of Chapter 3 and 4 build on Chapter 2 by including the influence of a steric environment. Chapter 3 demonstrates by application to a molecular gyroscope that extreme long-range correlated motion can be captured with GSM, and Chapter 4 details how the one-bond flip and hula-twist mechanisms are suppressed by the crystal cavity, the nature of the seam space in steric environments, and the features of the bicycle pedal mechanism. For example, the bicycle pedals rotate through the passageway in the adjacent monomers. However, the models do not capture the quantitative activation barriers and more work is needed. Finally, Chapter 5 provides the ultrafast details of how the photoacid isomerizes and ring-closes with experimental and computational evidence. Unfortunately, quantitative calculation of pKa cannot be provided with the computations employed herein. In summary, this thesis provides an advancement in the knowledge of photochemical mechanisms that can be used for the development of new syntheses and offers new tools with capacity to study complex photochemical problems.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/163005/1/craldaz_1.pd

Development of Polymeric Materials Chemistry via Physical Organic Simulations

Computational chemistry is an important and increasingly useful branch of chemistry. New technology has enabled faster and more accurate computations which allow researchers to quickly provide insights to experimentalists in real time. In order to do this, tools which allow for the discovery and prediction of new chemistries must be implemented. Chapter 1 provides an overview of computational chemistry and focuses on advancements in reaction discovery. In chapter 2, these methods are applied to reactions that encompass a wide range of transformations from the field of mechanochemistry. Mechanically induced reactions often have unique selectivities or mechanisms compared to traditional means of activation (photo, catalytic, thermal) due to perturbations from the applied force to the underlying potential energy surface. Growing String Method with a newly developed force functionality proves to be useful in determining transition states and reaction paths on complicated, force-biased potential energy surfaces, and as a result, new chemistries are discovered. The ability to elucidate the details of three complex reactions is demonstrated in finding cis and trans isomers of the spiropyran to merocyanin transformation at varying magnitudes of force, in uncovering the fundamental means of flex mechanophore activation, and in showing the physical principles of force-transmittance through different polymer backbones. Chapter 3 describes the first mechanistic study of the metal-free redox-mediated ring-opening metathesis polymerization (ROMP) process which yields poly(norbornene) of tunable cis and trans content. The ability to modulate product content is demonstrated by varying parameters such as reaction conditions (solvent, temperature, time), counter anion size, and size and donating ability of the R-group on the initiator. The trans product is favored under most conditions, but product content can be shifted toward cis when the cation is sufficiently destabilized. Modifying the R-group on the initiator is found to be stereo-electronically important. Overall, computations provide key insights into the mechanism for stereoselectivity that allows for the potential to generate ROMP polymers with highly tunable microstructures. In chapter 4, a bimetallic catalyst that yields highly isotactic poly (propylene oxide) is explored. The molecular geometry of the catalyst is determined to be in the closed conformation with head-to-tail stacking. A kink in the salen ligand is found to be energetically accessible. This geometric distortion may allow for less congested monomer addition and better molecular weight control. Computations are used to make a series of substitutions on the catalyst in order to establish structure-reactivity and structure-selectivity relationships. Chemical features such as SN2 angle and bond formation distance are used to describe these relationships in the first detailed mechanistic exploration of this version of the catalyst. The concluding chapter reflects on each of the projects described within the dissertation and discusses open areas for future consideration. Overall, this work outlines applications of modern computational tools to better understand polymeric materials chemistry.PHDChemistryUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/162949/1/kellyalg_1.pd