1. Computational Study of Substitution Effects in Acetylenic Diels-Alder Reactions Emily Sotelo Mentor Dr. Adam Moser

2. Overview  Background  Research Motivation  Methods: Quantum Chemistry  Calculations  Results  Implications for future work

3.  Discovered by chemists Otto Diels and Kurt Alder in 1928-recognized with a Nobel Prize in Chemistry in 1950 The Diels-Alder Reaction

4. Importance of the Diels-Alder Reaction 2. High Stereochemical Control 1. Ring Formation

5. Reaction Components Energetically favorable due to formation of new σ bonds Diene only reacts in s-cis conformation Electron withdrawing groups activate the dienophile Concerted mechanism Kinetic control can dominate

6. Reaction of Interest

8. Literature Review  The Diels-Alder Reaction of Acetylene is slower than that of Ethylene  Higher activation energy due to distortion energy  Only performed in lab using catalysts & radicals  Adding activating groups to both ends of the triple bond increases the reactivity

9. My Research  Seems to be this gap in the literature discussing the very basic components of this very important reaction of acetylene and butadiene  We have decided to study this computationally because you can examine lot reaction properties quickly

10. Quantum Chemistry Method  Describes what approximation will be used to solve the equation Basis Set  Describes what math is available to solve this equation Branch of computational chemistry which uses mathematical approximations to solve the Schrödinger equation

11. Substituents

12. Calculations  ΔH, ΔG, Δ‡H, and Δ‡G  HOMO-LUMO Energies

13. Single Substitution EWG

14. HOMO-LUMO

15. Single Substitution EDG

16. Double Substitution

17. Dihedral Scan

24. Summary  Most effective substituent to lower activation barrier  Lowers LUMO energy  This barrier is lowered further by substituting both ends of the triple bond  Steric effects seem to be the dominating force when locking the conformation of the dienophile

25. Next Steps  Continue to work with more substituents to see if these trends continue  Substitute both reactants to gain a better understanding of not only thermodynamics/kinetics but stereochemistry  Continue to work with the dihedral scanning  Use higher, more accurate levels of theory to  See if trends continue  Closer to experimental data

26. Acknowledgments  Dr. Adam Moser  Dr. Sean Mulcahy  Science Hall faculty  Loras College  Peers, Friends and Family

27. References  Cramer, C.J. (2002). Essentials of Computational Chemistry. Hoboken, NJ: Wiley.  Dai, M, Sarlah, D, Yu, M. Danishefsky, S, Jones, G, Houk, KN. 2006. Highly Selective Dielss-Alder Reactions of Directly Connected Enyne Dieneophiles. J Am Chem Soc 129, 645-657.  Froese, RDJ, Coxon, JM, West, SC, Morokuma, K. 1997. Theoreical Studies of DA reaction of Acetylenic Compounds. J. Org. Chem 63, 6991-6996.  Nicolaou KC, Snyder SA, Montagnon T, Vassilikogiannakis G (2002). The Diels-Alder Reaction in total synthesis. Angew Chem Int Ed 41: 1668-1698.  Rahm, A., Rheingold, A.L, Wulff, WD. 2000. Asymmetric Diels-Alder Reactions with Chiral Acetylenic Carbene Complexes as Dienophiles. Tetrahedrom 56, 4951-4965  Smith, J. (2011). Organic Chemistry 3 rd Edition. New York, NY: McGraw-Hill.

29. EXTRA SLIDES

30. Δ‡G Thermodynamic vs. Kinetic Control

31. Reaction Profile & T-State Calculations

32. Quantum Chemistry Method: Hartree Fock  Treats each electron separately  Assumes frozen nucleus Basis Set: 6-31G(d)  Equations which describe the shape of the orbital  Slater and Gaussian  The basis set is a split valance meaning there are two types of electrons, core and valence electrons with the valence electrons participating in the reaction behavior of molecule.  Split valence basis sets uses this knowledge to treat these two types of electrons differently.

33. HOMO-LUMO

35. Changing Levels of Theory