Chemo- and Stereoselective Olefin Metathesis in Small Molecule Synthesis

Citation

Funk, Timothy William (2007) Chemo- and Stereoselective Olefin Metathesis in Small Molecule Synthesis. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/25WJ-J768. https://resolver.caltech.edu/CaltechETD:etd-06152006-110234

Abstract

The major goals of the work described in this thesis were to expand the selectivity of ruthenium metathesis catalysts to include chemo- and stereoselective reactions and to apply those reactions to the synthesis of important organic compounds.

Chapter 2 describes efforts to synthesize trisubstituted vinyl boronates using the cross-metathesis of 1,1-disubstituted vinyl pinacol boronates. The reactions with methyl-substituted substrates afforded products in modest yields (up to 60%), and the reactions were typically highly selective for the Z-alkene. As the size of the substituent increased, the yields and stereoselectivities decreased. The lack of reactivity of certain ruthenium catalysts in the formation of trisubstituted alkenes lent insight into how to develop a chemoselective reaction where a monosubstituted olefin would exclusively react in the presence of a more highly substituted olefin.

Chapter 3 describes how conjugated dienes were synthesized by taking advantage of the large reactivity difference between monosubstituted alkenes and 1,1-disubstituted alkenes. The cross-metathesis reactions were highly chemo- and stereoselective, and only the E-isomer of the products was formed. Additionally, further functionalization of the diene products was shown to be possible in a one pot cross-metathesis/Suzuki coupling process.

The research presented in chapters 4 and 5 focused on the asymmetric ring-closing metathesis of achiral trienes using chiral ruthenium catalysts. Chapter 4 describes how substitution on the chiral catalyst and the substrate affected the enantioselectivity of the ring-closing reaction. It was discovered that certain five, six, and seven membered rings could be made in up to 92% ee with the chiral ruthenium catalysts. The application of asymmetric ring-closing metathesis in the synthesis of (+)-5-epi-citreoviral is presented in chapter 5. The absolute configuration of one chiral center was set using asymmetric ring-closing metathesis, and the remaining three stereocenters were set from that chiral center.

In addition, there are two appendices. Appendix 1 contains comments on the formation of tetrasubstituted olefins using unhindered ruthenium catalysts. The results from research directed toward the generation of a cis-selective olefin metathesis catalyst bearing a bidentate ligand are described in appendix 2.

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