Studies on the development of synthetic routes to enediynes.

Abstract

The thesis investigates synthetic routes to enediynes, a class of compounds of widespread interest due to their unusual molecular structure, potent antitumor activity and interesting mode of action. The preparation of eleven and twelve membered ring enediynes bearing oxy substituents in both propargylic positions is described via a novel intramolecular samarium diiodide coupling reaction of $\alpha,\beta$-unsaturated acetylenic aldehydes.* Other synthetic strategies based on various cyclization reactions (crossed aldol condensation, acetylide electrophile reaction, silicon directed electrophilic substitution and low valent palladium coupling) were examined.* A new anti-Brook rearrangement of acetophenone enol ethers was discovered that allows regiospecific migration of the silicon from oxygen to the ortho position of the aromatic ring. The enolate generated in the process allows tandem electrophilic reactions to be carried out at the carbon $\alpha$ to the carbonyl.* It was found that titanium tetrachloride induced the rearrangement of TMS acetylene derivatives providing an interesting entry to unsaturated exocyclic cyclopentanes.* The reaction of silyl substituted zinc/aluminum acetylides with ketals yields the corresponding propargylic ethers in a single step.* These findings provided useful solutions to the synthesis of the target compounds and hold promise for further utilization in the field of enediyne chemistry. ftn*Please refer to the dissertation for diagrams.