| Investigations into the total synthesis of vinigrol (1) are reported. The initial approach examined the intramolecular Diels-Alder reaction of triene 94 to adduct 95. Synthesis of 94 was accomplished using a diastereoselective Mukaiyama aldol coupling,* followed by sequential formation of the silyl enol ether moieties. Thermal reactions of this triene provided no cycloadduct, instead affording only migration of the trisubstituted enol ether to the thermodynamically favored tetrasubstituted isomer.; The attempted application of cation radical methodology to the Diels-Alder reaction of 94 prompted the synthesis of novel, rationally designed initiators of photoelectron transfer cation radical reactions. Triphenylpyrylium tetrakis[3,5bis(trifluoromethyl)phenyl]borate 136 was found to be an efficient catalyst for the [4+2] homodimerization of several silyl protected dienol ethers. This catalyst provides a useful extention of known methodology to incorporate readily available and synthetically practical substrates, but it was incapable of catalyzing the formation of 95.*; A second approach using the intramolecular inverse electron-demand Diels-Alder reaction of tetraene 239 was examined. The synthesis of this substrate featured several key steps, including: (1) directed lithiation of carvotanacetol (176) to install the necessary C(16) oxidation; (2) π-allyl palladium coupling of a carvone-derived allylic acetate with a stabilized ketone enolate to stereoselectively generate the hindered quaternary center; and (3) the epoxidation of a sensitive enone functionality to permit formation of the requisite methyl ester, followed by samarium. diiodide regeneration of the double bond. However, tetraene 239 decomposed rapidly under both thermal and Lewis acid catalyzed conditions.*; Additionally, an intermolecular inverse electron-demand Diels-Alder route was investigated. Tetracycles 262, 263, and 269 were synthesized by Lewis acid catalyzed cycloaddition from pyrones 247 and 268. This efficient formation of the vinigrol cis-decalin system incorporates all the necessary oxygenation in only two steps from known intermediates. However, the transannular eight-membered ring could not be installed.; *Please refer to dissertation for diagrams. |
