Synthesis of Heterocyclic Compounds via Intramolecular [4+2] Cycloadditions of Conjugated Enynes

Results from the systematic exploration of the scope of the intramolecular [4+2] cycloaddition of conjugated enynes revealed that the reaction is quite general. The synthetic utility of the intramolecular enyne cycloaddition for the synthesis of substituted polycyclic aromatic and dihydroaromatic heterocycles has been demonstrated. In the course of our investigation, we examined a variety of features of the reaction including substituent effects on the enyne, substituent effects on the enynophile, the effect of the length of the connecting chain, the effect of substitution in the connecting chain, and the use of alkenes as enynophiles in the reactions. From these studies, a number of generalizations can be made concerning the types of substrates that participate in the cycloaddition reaction. The mechanism of the intramolecular [4+2] cycloaddition of conjugated enynes was also examined. The results from mechanistic and stereochemical experiments have been disclosed along with mechanistic implications. Our investigation of the mechanism of the intramolecular enyne cycloaddition has provided important mechanistic information that supports either a biradical or cyclic allene intermediate in the thermal reactions, and either a dienyl cation, halodiene, or cyclic allene intermediate in the Lewis and protic acid-promoted reactions. Finally, from our stereochemical studies of substrates with an alkene as the enynophile, we have shown that the cycloaddition is concerted (or a stepwise mechanism in which ring closure of any intermediate is extremely fast), and proceeds with high endo selectivity. Thesis Supervisor: Rick L. Danheiser Title: Professor of Chemistry