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

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

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

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

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

Reaction of Interest

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

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

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

Substituents

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

Single Substitution EWG

HOMO-LUMO

Single Substitution EDG

Double Substitution

Dihedral Scan

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

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

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

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

EXTRA SLIDES

Δ‡G Thermodynamic vs. Kinetic Control

Reaction Profile & T-State Calculations

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.

HOMO-LUMO

Changing Levels of Theory