Chemistry and Biochemistry
Bayer School of Natural and Environmental Sciences
Alpha hydrogen bond, Lewis acid, Hydrogen bond, Stereochemistry, Density functional theory, Catalysis
In the field of asymmetric induction, there is a shift from the synthesis of reaction
specific chiral auxiliaries towards a broader mechanistic approach. Our approach is to
develop a theory of asymmetric catalyst design from first principles. The Diels-Alder
reaction of 2-methacrolein and 1,3-cyclopentadiene in the presence of 15 mole % lmenthoxy
aluminum dichloride, reported by Koga, achieved the (S)-exo-Diels-Alder
cycloadduct with 72% ee (0% ee Endo for acrolein). The dramatic change from 72% to 0%
ee is a significant fact that has been overlooked in practical organic synthesis.
In the first phase of this work, the conformational landscape of l-menthoxy
aluminum dichloride was probed and the most energetically favorable conformation was
found to be the all equatorial chair. In the second phase, the physical origin of the Corey-
Rohde formyl-hydrogen bond is determined. It was discovered that there are key crystal
packing forces we call the halogen pocket and electrostatic anchor that promotes the
observed formyl hydrogen bond.
In a direct comparison between the formyl, α, and the β hydrogen bond the Curtin-
Hammett principle is applied to a series of comparisons that are necessary to determine to
complete selectivity of Koga’s reaction. The competition between the formyl and alpha
hydrogen bond is examined to yield an enantiomeric excess of 35.1%. Principles of crystal
packing forces from chapter 4 are applied through solvents that induces the formyl
hydrogen bond and this principle. In the future we will apply explicit solvent molecules to
Koga’s reaction to reduce the computed stereoselectivity to 0%.
Vernier, B. (2019). Nontraditional hydrogen bonding in asymmetric Lewis acid catalysis (Doctoral dissertation, Duquesne University). Retrieved from https://dsc.duq.edu/etd/1794