Transition metal-catalyzed olefin hydroacylation represents an atom-economical approach for the synthesis of valuable ketone products. To date, the intermolecular variant of this reaction suffers from several drawbacks, which include limited substrate scope, poor reactivity and/or regioselectivity for non-activated, non-chelating alkene substrates, and competitive reductive decarbonylation pathways that lead to catalyst decomposition. Herein, we report the linear-selective intermolecular hydroacylation of a wide range of electronically diverse olefins with salicylaldehydes employing catalyst loadings as low as 2 mol%. A unique reactivity profile is observed for the chiral C2-symmetric phosphoramidite ligand employed in our catalyst system, and thus, we outline progress made towards the synthesis of new phosphoramidite ligands. We have applied our methodology in the total synthesis of nine octaketide natural products belonging to the dothiorelone, cytosporone, and phomopsin families. Due to recent reports demonstrating the anticancer activity of cytosporone B (Csn-B), we will also discuss progress towards the synthesis of Csn-B analogues.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/33305 |
| Date | 20 November 2012 |
| Creators | Le, Christine |
| Contributors | Dong, Vy Maria |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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