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Electronic Structure Evaluation of Competing Pathways in the Gold(III BearWorks MSU Graduate Theses Summer 2017 Electronic Structure Evaluation of Competing Pathways in the Gold(III)-Catalyzed Ohloff-Rautenstrauch Cyclosimerization Converting Propargylic Acetates to Carene-like Natural Products Jeremy M. Hines Missouri State University, [email protected] As with any intellectual project, the content and views expressed in this thesis may be considered objectionable by some readers. However, this student-scholar’s work has been judged to have academic value by the student’s thesis committee members trained in the discipline. The content and views expressed in this thesis are those of the student-scholar and are not endorsed by Missouri State University, its Graduate College, or its employees. Follow this and additional works at: https://bearworks.missouristate.edu/theses Part of the Organic Chemistry Commons, and the Physical Chemistry Commons Recommended Citation Hines, Jeremy M., "Electronic Structure Evaluation of Competing Pathways in the Gold(III)-Catalyzed Ohloff-Rautenstrauch Cyclosimerization Converting Propargylic Acetates to Carene-like Natural Products" (2017). MSU Graduate Theses. 3111. https://bearworks.missouristate.edu/theses/3111 This article or document was made available through BearWorks, the institutional repository of Missouri State University. The work contained in it may be protected by copyright and require permission of the copyright holder for reuse or redistribution. For more information, please contact [email protected]. ELECTRONIC STRUCTURE EVALUATION OF COMPETING PATHWAYS IN THE GOLD(III)-CATALYZED OHLOFF-RAUTENSTRAUCH CYCLOSIMERIZATION CONVERTING PROPARGYLIC ACETATES TO CARENE-LIKE NATURAL PRODUCTS A Master’s Thesis Presented to The Graduate College of Missouri State University TEMPLATE In Partial Fulfillment Of the Requirements for the Degree Master of Science, Chemistry By Jeremy Hines August 2017 Reproduced in part with permission from “One Lump or Two? A Plurality of Pathways in Gold(III)-Catalyzed Cyclization Transforming Propargyl Acetates to a Carene-like Bicyclo[4.1.0]heptane.” Jeremy M. Hines, Jesse J. Eason, and Matthew R. Siebert. Organometallics 2017 36, 920-926. Copyright 2017, American Chemical Society. Copyright 2017 by Jeremy Michael Hines ii ELECTRONIC STRUCTURE EVALUATION OF COMPETING PATHWAYS IN THE GOLD(III)-CATALYZED OHLOFF-RAUTENSTRAUCH CYCLOSIMERIZATION CONVERTING PROPARGYLIC ACETATES TO CARENE-LIKE NATURAL PRODUCTS Chemistry Missouri State University, August 2017 Master of Science Jeremy Hines ABSTRACT Propargylic acetates can lead to complex transformations upon exposure to a gold catalyst. Gold catalyzed transformations also allow for simple synthesis of a number of natural products. Gold (III)-cycloisomerization of a 5-acetoxy-1,6-enyne is reported to proceed through two pathways that differ in the order of major events: cyclization followed by ester migration (“cyclization first”) or the reverse (“migration first”). Both pathways could theoretically proceed in either order. This rearrangement is called the Ohloff-Rautenstrauch rearrangement and has high regio- and stereocontrol affording a bicylo[4.1.0]heptane carbon substructure. This rearrangement allows for the synthesis of the carene class of natural products. Computational modeling determining the mechanism and preference for the pathways in the gas- and solvent-phase (dichloroethane, IEFPCM) are described herein. Structures for the pathways are found using the B2PLYP/6-31G(d)- LANL2DZ model chemistry while energies are found at the B2PLYP- D3/def2TZVP//B2PLYP/6-31G(d)-LANL2DZ level. Both pathways feature multiple steps with low energy barriers. Highest-energy structures for both pathways are close in energy (∆∆E‡ = 2.8 kcal/mol for solvent phase). Turnover frequency for each pathway are calculated suggesting that the cyclization first pathway may dominate. KEYWORDS: DFT, gold (III), propargylic acetate, carene, natural products This abstract is approved as to form and content _______________________________ Matthew R. Siebert, PhD Chairperson, Advisory Committee Missouri State University iii ELECTRONIC STRUCTURE EVALUATION OF COMPETING PATHWAYS IN THE GOLD(III)-CATALYZED OHLOFF-RAUTENSTRAUCH CYCLOSIMERIZATION CONVERTING PROPARGYLIC ACETATES TO CARENE-LIKE NATURAL PRODUCTS By Jeremy Hines A Masters Thesis Submitted to the Graduate College Of Missouri State University In Partial Fulfillment of the Requirements For the Degree of Master of Science August 2017 Approved: _______________________________________ Matthew R. Siebert, PhD. _______________________________________ Gary A Meints, PhD. _______________________________________ Maria Stepanova, PhD. _______________________________________ Gautam Bhattacharyya, PhD. _______________________________________ Julie Masterson, PhD: Dean, Graduate College iv ACKNOWLEDGEMENTS I dedicate this thesis to my parents for their endless support and encouragement. v TABLE OF CONTENTS Gold Reactivity ....................................................................................................................1 Gold Properties ........................................................................................................1 Alkene Activation ........................................................................................3 Alkyne Activation ........................................................................................4 Reactions of Gold and Alkynes ...............................................................................7 Oxygen Nucleophiles ...................................................................................7 Carbon Nucleophiles ....................................................................................9 Conclusion .............................................................................................................16 Theoretical Background .....................................................................................................18 Introduction ............................................................................................................18 Potential Energy Surface........................................................................................18 Quantum Chemistry ...............................................................................................19 Basis Sets ...................................................................................................22 Slater Determinant .....................................................................................23 Hartree-Fock Method .................................................................................24 Densitry Functional Theory (DFT) ............................................................25 Functionals .....................................................................................26 Dispersion Correction ....................................................................28 Solvation ....................................................................................................29 Conclusion ........................................................................................................29 Gas Phase Calculation........................................................................................................31 Methods..................................................................................................................31 Results ....................................................................................................................33 Overall Reaction ........................................................................................33 Migration first pathway..............................................................................33 Cyclization first pathway ...........................................................................38 Conclusion .............................................................................................................42 Solvent Phase Calculations ................................................................................................43 Methods..................................................................................................................43 Results ....................................................................................................................44 Overall Reaction ........................................................................................44 Migration first pathway..............................................................................44 Cyclization first pathway ...........................................................................50 Conclusion .............................................................................................................53 Conclusions .......................................................................................................................55 References ..........................................................................................................................62 vi LIST OF TABLES Table 1. Difference in energy for Rate-limiting TSSs with various model chemistries. ...56 vii LIST OF FIGURES Figure 1.Synthesis of oxazoline ...........................................................................................3 Figure 2. Orbital interactions of metal-ethylene bonding ....................................................4 Figure 3. Orbital diagrams showing metal – acetylene interaction .....................................5
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