Disputation: Bridging McMurry and Wittig in One-Pot: Olefins from Stereoselective, Reductive Couplings of Two Aldehydes via Phosphaalkenes

  • Date:
  • Location: Ångströmlaboratoriet, Lägerhyddsvägen 1 Häggsalen
  • Doctoral student: Mai, Juri
  • About the dissertation
  • Organiser: Synthetic Molecular Chemistry
  • Contact person: Mai, Juri
  • Disputation

The formation of C=C bonds is of great importance for fundamental and industrial synthetic organic chemistry. There are many different methodologies for the construction of C=C bonds in the literature, but currently only the McMurry reaction allows the reductive coupling of two carbonyl compounds to form alkenes. This thesis contributes to the field of carbonyl olefinations and presents the development of a new synthetic protocol for a one-pot reductive coupling of two aldehydes to alkenes based on organophosphorus chemistry. The coupling reagent, a phosphanylphosphonate, reacts with an aldehyde to yield a phosphaalkene intermediate which upon activation with a base undergoes an olefination with a second aldehyde. A general overview of synthetic methods for carbonyl olefinations and the chemistry of phosphaalkenes is given in the background chapter. The Wittig reaction and its variations are discussed in detail.

The synthesis, reactivity, properties and applications of phosphaalkenes are highlighted with particular focus on strategies to stabilize these otherwise reactive species. The third chapter describes a novel method for the reductive coupling of aldehydes. The activation of phosphaalkene intermediates by a hydroxide base, mechanistic studies, development of a one-pot procedure and investigations of the substrate scope are discussed. The new one-pot reaction is advantageous over the McMurry coupling since it allows the formation of unsymmetrical E-alkenes under mild conditions. The next chapter is dedicated to a modification of the reaction sequence.

The results show that activation of the phosphaalkene with an alkoxide instead of hydroxide, followed by oxidation, generates a more reactive transient species that can undergo the coupling with electron rich (deactivated) aldehydes which was not possible under the initial reaction conditions. Chapter five describes a modification of the phosphanylphosphonate reagent that enables the preparation of alkenes with high Z-stereoselectivity. In the final chapter, chemical equilibria studies of triphenylphosphaalkenes are presented. It is found that phosphaalkenes with poor kinetic stabilization can also be used as intermediates in the carbonyl-to-alkene coupling chemistry. In summary, this thesis presents the development of an unprecedented synthetic method for the direct formation of C=C double bonds from two aldehydes together with strategies on improvements of the substrate scope and modifications to control the stereochemical outcome of the reaction.