| Part one of this two-part thesis describes the enantioselective construction of compounds containing a quaternary carbon center by the alkylation of alpha,alpha-disubstituted pseudoephedrine amides. Stereodefined alpha,alpha-disubstituted enolates of pseudoephedrine amides were formed by (1) the deprotonation of alpha,alpha-disubstituted pseudoephedrine amide substrates with lithium diisopropylamide, or (2) the conjugate addition of organolithium reagents to alpha-substituted pseudoephedrine acrylamide substrates. Alkylation of alpha,alpha-disubstituted pseudoephedrine amide enolates was demonstrated to be both high yielding and diastereoselective across a range of substrates. Methods are presented to transform the pseudoephedrine amides bearing an alpha-quaternary carbon center into optically active carboxylic acids, ketones, primary alcohols, and aldehydes.;In part two of this thesis, a new preparation of enone 23, the key precursor to fully synthetic tetracycline antibiotics, is detailed. The A-ring of enone 23 was formed by a highly diastereoselective Michael-Claisen coupling reaction of cyclohexenone 49 and isoxazole ester 50 to provide the cycloadduct 55. High-temperature thermolysis of 55 expelled cyclopentadiene to afford the retro-Diels-Alder product 56. Compound 56 was converted into enone 23 in three steps, which included stereoselective hydroxylation of C12a and epimerization of C4. In a refinement to the route, the dimethylphenylsilyl-substituted cyclohexenone 70 was employed. Silyl-substitution improved the yield and reproducibility of the retro-Diels-Alder fragmentation step. Furthermore, many intermediates containing the dimethylphenylsilyl group were crystalline which allowed the sequence to be scaled without resort to purification by chromatography.*;*Please refer to dissertation for diagrams. |
