Efforts Toward the Synthesis of Taxane Natural Products

Studies for this thesis involve efforts toward the enantioselective total synthesis of taxusin (5). Key features of the synthetic sequence include a diastereoselective, intramolecular enone-olefin [2+2] photocyclization of photosubstrate 94 which introduces the correct stereochemistry of the C(8) methyl group. This reaction represents an unprecedented total reversal of stereochemistry from the photocyclization of photosubstrate 53 through the substitution of an aromatic ring. Another key feature of this study is the fragmentation of cyclobutane intermediate 93 with lithium and liquid ammonia which results in the selective formation of either cyclooctanone 92 or cyclooctanone 137, each as a single diastereomer. Cyclooctanone 92, which incorporates the correct trans stereochemistry across the B-C ring juncture of taxusin, is selectively formed by using a nearly stoichiometric amount of lithium in the reaction mixture, while cyclooctanone 137 is obtained selectively by using an excess of lithium in the reaction vessel.