| Gold-catalysis has emerged as a powerful tool for the synthetic community, allowing for new transformations that are not easily accessed through other methods. Detailed in this dissertation, are the studies leading to a gold-catalyzed dehydrative cyclization to form azacycles via an intramolecular SN2 ' type allylic alkylation reaction. Formation of the desired heterocycles occurs through the nucleophilic attack of a tethered nitrogen nucleophile on an allylic alcohol that is rendered electrophilic by a gold-catalyst. During these cyclization studies, an efficient transfer of chirality was observed. Interestingly, with cation stabilizing substituents in the allylic position a competing ionization pathway was observed.;Allylic alcohols are commonly used as electrophiles in dehydrative cyclization reactions, however, their use as nucleophiles is described here in the context of an efficient gold-catalyzed tandem hydroalkoxylation/Claisen rearrangement. This reversal in reactivity posed a significant challenge which required tuning the reaction conditions to circumvent the SN2' side reactions and allow for selective hydroalkoxylation of the alkyne reaction partner. Fortunately, optimized conditions were found that gave facile formation of the desired gamma, delta-unsaturated ketones. Successful implementation of this synthetic methodology provides a new protocol for rapidly building complex acyclic ketone products from an allylic alcohol and an alkyne. Additionally, the observed diastereoselectivities for the tandem process have given invaluable insight into the possible mechanistic pathways. During our studies of a gold-catalyzed Claisen rearrangement, an efficient sequential gold-catalyzed enol formation/ruthenium-catalyzed [1,3]-O to --C migration was also developed. The process allows for rapid access to highly functionalized cyclic ketone products in a highly diastereoselective fashion. |
