This dissertation represents our preliminary mechanistic
investigations on the silylation-based kinetic resolution of secondary
alcohols, and how we use that knowledge for further expansion of this
methodology. Chapter 2 describes how we came up with a preliminary
mechanism of our silylation-based methodology using a linear free energy
relationship and a rate study. In this chapter, several para
substituted triphenylsilyl chlorides were prepared that varied
electronically and sterically in order to understand the substituent
effects on the rate and the selectivity of the reaction. Selectivity
factors and initial rates were experimentally determined for the kinetic
resolution reactions with the newly designed silyl chlorides. Linear
free energy relationships were found to correlate both selectivity
factors and initial rates.
Chapter 3 covers our 29Si NMR studies in order to understand if a
complex is forming between the catalyst (-)-tetramisole and Ph3SiCl. A
variety of different techniques were used including 1H NMR titrations,
29Si NMR experiments, and 1H-29Si gHSQC 2D experiments. Finally, three
different mechanisms were proposed for future study.
Chapter 4 discusses our efforts to apply the silylation-based
methodology developed by the Wiskur lab to allylic alcohols, homoallylic
alcohols, and 2-arylcyclohexanols. No enantiodiscrimination was
obtained with allylic alcohols and homoallylic alcohols while a moderate
level of selectivity was achieved with 2-arylcyclohexanols. Employing
Ph3SiCl substituted in the para position with an isopropyl group in the
kinetic resolution reaction of 2-arylcyclohexanol resulted in a doubling
of the selectivity factor. The synthesis of various substrates and
employing them in our kinetic resolution is discussed.
Chapter 5 describes the use of a polymer supported triphenylsilyl
chloride in our kinetic resolution reaction. Different molecular weight
polymers containing triphenylsilyl chloride were prepared and tested in
the kinetic resolution of 4-chromanol. Similar selectivity factors were
reported in all cases. Reaction optimization along with future work for
this project is discussed.
Finally, Chapter 6 explores our attempt toward the development of a
kinetic resolution of amines by transforming them into imines and
employing them in an asymmetric aza-Diels-Alder reaction. Various chiral
Lewis acids were attempted to achieve selectivity in the
aza-Diels-Alder reaction.