Two organic synthetic methods for the generation of methyl bearing chiral centers have been developed using: 1) dimerization of methylketene and 2) a free radical-based addition/elimination reaction involving allyl bromides. The first method, the asymmetric dimerization of methyl ketene, followed by an asymmetric aldol reaction and the appropriate functional group manipulations enabled us to construct the (2S, 4S, 6S) trimethylnonyl subunit found in the siphonariene class of natural products. The latter method explored the stereoselective potential of a free radical-based condensation reaction by examining compounds which are known to be able to support chiral auxiliaries and chiral Lewis acids. Additionally, substituent effect on the rates of this reaction were examined closely and found to be comparable to similar, previously examined systems. The synthetic utility, magnitude and scope of this reaction are discussed. / Ph. D.

A new free radical chain process for the allylation of hydrocarbons and some other substrates utilizing substituted allyl bromides (R-H + C=C-C-Br -> R-C-C=C + HBr) has been developed. Good to excellent yields were observed in all cases. Kinetic chain measurements and competition experiments were performed in order to elucidate the mechanism of the reaction. Overall, the results are consistent with a free radical chain process with bromine atom as the chain carrier. Substitution effects on the reactivity of the allyl bromides (CH2=C(Z)CH2Br) and their influence on the overall reaction rate were studied by conducting several competition experiments. The relative rate constants for addition of benzyl radical to CH2=C(Z)CH2Br are: Z=CN(180), COOEt(110), Ph(65), H(1.0). The trend of electronegativity/reactivity of these reactions was very similar to that reported for addition of benzyl radical to substituted alkenes. Other than alkyl aromatics (PhCH3, PhCH(CH3)2), other substrates (i.e., 2- propanol, phenyl cyclopropane) were also tested for this allylation reaction. The magnitude and scope of these reactions, and their synthetic utility is discussed. / Ph. D.