Mechanistic rationale of pseudophedrine as a chiral auxiliary, NMR investigation and synthesis of novel auxiliaries

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Awarding institution
  • University of Strathclyde
Date of award
  • 2011
Thesis identifier
  • T13491
Qualification Level
Qualification Name
Department, School or Faculty
  • Myers has investigated pseudoephedrine as a highly selective chiral auxiliary for the alkylation of amide enolates. The aim of this project was to probe the currently accepted mechanistic rational of the pseudoephedrine amides as it is in dispute. The suggested mechanism is that the diastereolectivity is due to the pseudoephedrine alkoxide that blocks the 1Si,2Re face. However, a new hypothesis was put forward thanks to DFT calculations: it may be the aromatic ring that interacts with the enolate lithium cation which provides the shielding of that specific face. In order to probe this hypothesis a NMR investigation, including ¹H, ¹³C, nOe signals, chemical shift measurements and J values, was carried out on the pseudoephedrine amide, the alkoxide and the enolate. Analysis of the latter was unsuccessful. However, the analysis on the pseudoephedrine amide and alkoxide show that these two compounds exist as two rotamers and are in an extended conformation differing only by the conformation of the α-proton with the N-methyl group. Moreover, two new pseudoephedrine derivatives with a fully reduced aromatic ring have been synthesised in two steps.
Resource Type
Date Created
  • 2011
Former identifier
  • 991648