Kalstabakken, Kyle A.2014-07-072014-07-072014-05https://hdl.handle.net/11299/163769University of Minnesota Ph.D. dissertation. May 2014. Major: Chemistry. Advisor: Andrew Michael Harned. 1 computer file (PDF); xviii, 441 pages, appendices I-II.2,5 Cyclohexadienones are versatile synthetic building blocks that are currently underutilized in natural product synthesis. The desymmetrization of symmetrically substituted cyclohexadienones is a strategy for the asymmetric synthesis of complex frameworks that has been rapidly gaining popularity. Two desymmetrization methodologies developed by our group are described herein.The first is a phase-transfer catalyzed intramolecular Michael addition of malonate-tethered cyclohexadienones mediated by <italic>Cinchona</italic> alkaloid-derived ammonium salts. Under these conditions, bicyclic lactones are formed in enantiomeric ratios of up to 91:9. For unsymmetrically substituted substrates, the regioselectivity of the reaction is governed by a combination of steric and electronic affects: cyclization occurs away from sterically bulky substituents and towards electron-withdrawing substituents. In the case of brominated substrates, unique tricyclic cyclopropanes are obtained.The second methodology is a Pd-catalyzed intramolecular enyne reaction of alkyne-tethered cyclohexadienones. This cyclization occurs with enantiomeric ratios of up to 81:19 in the presence of bipyridine-based chiral ligands. Substituents on the cyclohexadienone core were found to have a great influence on the both the selectivity and the efficiency of the reaction, which can likely be attributed to steric effects.Finally, the use of the phase-transfer catalysis methodology in the total synthesis of the briarane family of natural products was explored. In the pursuit of a key intermediate containing the briarane core, it was discovered that the enolates of the bicyclic lactone products are particularly unstable, and are not amenable to functionalization. Further studies toward this goal are underway.en-USCyclohexadienonesDesymmetrizationSynthesisThesis or Dissertation