| Camphor-derived chiral auxiliaries containing an α-heteroatom were deprotonated and trapped with electrophiles to give alkylation products along with decomposition products. Surprisingly, the absolute stereochemistry of the alkylation product was not affected by changing the counterion of the base but by changing the structure of the chiral auxiliary. The enolate decomposition to a ketene and metalated lactam was shown to be reversible, leading to revision of the stereochemical model. A thiolactam was used to change the strength of the lithium chelate but it was insufficiently reactive. Increasing the steric size of the ketene led to an irreversible decomposition pathway. An asymmetric alkylation reaction was used to improve the route to an intermediate in the synthesis of the natural product, tetronolide.; A stereochemical proof and total synthesis of the apoptosis-inducing natural product, rasfonin, was initiated. Installation of the hydroxymethyl group to form the single stereocenter of the diene ester chain was investigated. The two methyl groups of the alkyl sidechain were introduced using asymmetric alkylation and aldol reactions. The Mukaiyama aldol reaction of tert -butyldimethylsiloxy furan with a chiral aldehyde will be used to synthesize the precursor for the key reaction, so a model was used to determine the relative stereochemistry of the two new stereocenters. Conditions for the key rearrangement of an unsaturated five-membered lactol to the six-membered lactol with concomitant acyl group transfer were found and this reaction was demonstrated on a simplified substrate. |
