Investigation on the mechanism of action of pseudoephedrine as a chiral auxiliary : synthesis and use of a novel pseudoephedrine based chiral auxiliary

Awarding institution
  • University of Strathclyde
Date of award
  • 2010
Thesis identifier
  • T12789
Qualification Level
Qualification Name
Department, School or Faculty
  • In 1997, Myers reported pseudoephedrine to be a highly selective chiral auxiliary for alkylation of amide enolates. To account for the diasteroselectivity a reactive conformation was postulated. This reactive conformation was suggested to benefit from steric screening by a lithium alkoxide that may be further linked to the lithium enolate. However, later studies threw into question Myers' postulated mechanism of action of pseudoephedrine as an auxiliary. The purpose of this project was to explore the mechanism of action of the pseudoephedrine chiral auxiliary in order to get a better understanding of the origin of the diasteroselectivity and, therefore, to increase the steroslectivity by synthesizing appropriate analogues. DFT calculations suggest that the aromatic ring of the auxiliary may interact with the enolate lithium cation. Our hypothesis postulates that increasing the electron density of the aromatic ring of the pseudoephedrine will increase its selectivity. Thus, a route of synthesis of analogues of pseudoephedrine allowing us to modify the electron density of the benzyl ring was designed. An analogue, the 3,5-dimethylphenyl pseudoephedrine analogue, was synthesized with high diastereopurity which was confirmed by X-ray analysis. Comparison of the selectivity of acylated derivatives of this new analogue against the pseudoephedrine's using a standard enolate alkylation reaction was investigated.
Resource Type
Date Created
  • 2010
Former identifier
  • 823952