Enantioselective formation of propargylic alcohols

• Author / Creator

  Sullivan, Erin Rae

• Propargylic alcohol natural products are found in many species of terrestrial plants and marine organisms. Because these compounds are usually isolated from the natural source in only small amounts, few studies of propargylic alcohol natural products have been conducted to date. Nevertheless, these studies show compounds with this backbone have diverse biological activities and potential for pharmaceutical applications. Recently, routes have been developed for the asymmetric addition of monoynes to aldehydes, forming propargylic alcohols in high enantioselectivities. At the commencement of this thesis research, however, little work had been reported toward the asymmetric addition of polyynes to aldehydes. As outlined in Chapter 1, the polyynol functionality is quite prevalent in nature, and therefore efficient synthetic routes to this framework could provide compounds to help improve our understanding of the origin of their diverse biological activities. Chapter 2 addresses the asymmetric addition of terminal di- and triynes to aldehydes along, with a one-pot Fritsch-Buttenberg-Wiechell rearrangement-asymmetric addition reaction. The asymmetric addition of terminal diynes and triynes would be a more direct route to polyynol natural products, avoiding the use of tedious cross-coupling reactions. The one-pot protocol would again be a more expedient route and would circumvent the isolation of an unstable terminal polyyne.
  A second functional group that has shown wide application in natural product synthesis is the homoallylic propargylic alcohol moiety, as it contains three distinct synthetic handles: the alkyne, alkene and alcohol. The most direct route to a homoallylic propargylic alcohol is to perform an allylation reaction on a propargylic aldehyde. The most frequent allyl transfer method applied in natural product synthesis is an allylation with an allylboron reagent known as an allylboration reaction. Despite the popularity of this framework, no catalytic asymmetric allylboration reaction currently exists for propargylic aldehydes. Current methodologies to homoallylic propargylic alcohols either apply a stoichiometric amount of a chiral allylborane or the use of harsh allyl metal species. Chapter 3 describes the catalytic asymmetric allylboration of propargylic aldehydes.

• Subjects / Keywords

  • Polyyne
  • Alcohol
  • Natural products
  • Enantioselective
  • Propargylic

• Graduation date

  Fall 2011

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3WW8X

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.