Chiral phosphoric acid-catalyzed asymmetric protonation reactions of vinylheteroaryls

  • Matthew Ashford

Student thesis: Doctoral Thesis (PhD)


This thesis describes investigations into the chiral phosphoric acid-catalyzed aza-Michael addition-asymmetric protonation between arylamines and various α-substituted vinylheterocycles.

Initially, research focused on the development of optimal reaction conditions for the aza-Michael addition-asymmetric protonation reaction of arylamines and fluorovinylheterocycles, furnishing heterocyclic phenethylamine products containing benzylic stereocentres with a carbon-fluorine bond in good yields (up to 95%) and enantioselectivity (up to >99:1 e.r.). Investigation into the asymmetric protonation step was carried out through DFT calculations and kinetic experiments, this provided evidence for a stereocontrolled proton transfer from catalyst to substrate. Additionally, the conformation of the heterocyclic phenethylamine products was explored through DFT calculations and XRD.

Chlorovinylheterocycles were also investigated within the aza-Michael addition- asymmetric protonation reaction, furnishing heterocyclic phenethylamine products containing benzylic stereocentres with a carbon-chlorine bond in good yields (up to 99%) and enantioselectivity (up to 99:1 e.r.). Development of a one-pot aza-Michael addition- asymmetric protonation-ring closure reaction was also carried out to furnish chiral heterocyclic aziridines in good yields (up to 81%) and enantioselectivity (up to 97:3 e.r.). Product derivatization of the chiral heterocyclic aziridines furnished chiral vicinal diamines in good yields (up to 84% yield) and enantioselectivity (up to 96:4 e.r.). Catalyst variation experiments showed the importance of steric interactions from the catalyst
alkyl groups in enforcing high enantioselectivity.
Date of Award15 Jun 2022
Original languageEnglish
Awarding Institution
  • University of St Andrews
SupervisorMatthew Ashford (Supervisor)

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