Defense Date

10-18-2018

Graduation Date

Spring 5-10-2019

Availability

One-year Embargo

Submission Type

dissertation

Degree Name

PhD

Department

Chemistry and Biochemistry

School

Bayer School of Natural and Environmental Sciences

Committee Chair

Jeffrey Evanseck

Committee Member

Bruce Beaver

Committee Member

Aaron Bloomfield

Committee Member

Jeffrey Rohde

Keywords

Alpha hydrogen bond, Lewis acid, Hydrogen bond, Stereochemistry, Density functional theory, Catalysis

Abstract

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

v

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%.

Language

English

Available for download on Sunday, May 10, 2020

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