| This dissertation is divided into two parts. The first part describes the dicobalt octacarbonyl mediated synthesis of medium sized rings via the intramolecular Pauson-Khand (IMPK) reaction. The cyclization of 1,8-enynes has proved to be difficult via the IMPK reaction due to entropy reasons. To overcome this limitation we attempted this cyclization in the presence of an ortho-buttressing group (t-butyl group) on the aromatic ring so as to reduce the conformationally allowed volume of the alkene arm of the substrate. The construction of the substrates started with O-alkenylation of the commercially available 3,5 di- tert-butyl-2-hydroxylbenzaldehyde and then the O-alkenylation products were alkynylated using ethynyl Grignard reagents to afford the corresponding enynes. These enynes successfully engaged in the both thermal and oxidative IMPK reaction to afford 5,7,6-tricyclic systems. With the parent enynes we observed diketo-compounds as the major product and traces of the expected PK product. When the alkyne arm of the enynes was substituted, the cyclization gave both the reduced PK product and the expected PK product. In general, the thermal mode gave a better diastereoselectivity when compared to the oxidative mode. Attempts to extend these result to a higher homolog to provide 5,8,6 tricyclic systems unfortunately failed. Thus this work describes a new methodology for the construction of medium (>6) sized rings via IMPK reaction.;A second system was investigated which examined whether highly congested systems, related to those found in the hamigeran benzannulated terpenes, could be constructed. These experiments were successful, setting the stage for the studies described in the second section.;The second part describes approach to the synthesis of the hamigerans by the application of the above developed IMPK methodology. The cyclization substrate was accessed from commercially available salicylic acid. The directed ortho metalation of the amide and treatment with iodine gave the iodo aryl amide. This was subsequently alkynylated using a Sonogashira cross-coupling reaction and then alkenylated via a Grignard reaction. The enyne was the subjected to IMPK reaction to afford the tricyclic core of the hamigerans. |
