A novel hetero Diels-Alder reaction has been developed to facilitate the synthesis of annelated pyridines as models for pyridoacridine alkaloids. The key reaction is based on an intramolecular Diels-Alder reaction of an aza-1,3-butadiene with an appropriate dienophile, to yield the desired annelated pyridine. An extension of this methodology is to exploit the Eglinton copper (IT) dimerisation of terminal acetylenes. This allows for a unique double intramolecular hetero Diels-Alder reaction, where four new rings are formed in one step. This allows for a facile route to annelated bipyridines. Ultimately this methodology has led to an approach to the total synthesis of the natural product eilatin, a member of the class of compounds known as pyridoacridines.

An extensive study of disubstituted cycloalkanes like CnH2n where n=3,4,5 and 6 using DFT((U)B3LYP/6-31G(d) and 6-311+G(2df,2p)) calculations is presented focusing on the effect of pyramidalization of the radical center. A potential energy surface (PES) analysis shows that the radical prefers to pyramidalize anti to the two cis fluorines in the disubstituted cycloalkanes. The degree of pyramidalization for 1,2-difluorocyclopropyl radical is 43.9o away from the cis fluorines whereas for 1,3-difluorocyclobutyl radical, 1,3-difluorocyclopentyl radical and 1,3-difluorocyclohexyl radical is 3.8o, 5.4o and 14.5o respectively away from the cis fluorines. The importance of this pyramidality effect in these compounds is discussed in context with the carbon-hydrogen bond dissociation energies (BDE's) because the preference of the radical centers to pyramidalize anti to the fluorines affects the bond dissociation energy. Importance of steric effect and unfavorable electronic interactions have been extensively explored in planar permethylated cyclobutadiene (Me4CBD) and cyclooctatetraene (Me8COT) using ((U)B3LYP/6-31G(d) and 6-311+G(2df,2p)) calculations. It is thought that steric interactions dominate electronic interactions in Me8COT, while this works opposite in case of Me4CBT. Instead, in Me4CBD the number of unfavorable electronic interactions between π bonds and out-of-plane hydrogens plays the dominant role in determining the relative energies. Interactions between the π bonds of CBD and the out-of-plane hydrogens on carbons attached to the four-membered ring becomes very interesting when the ring size changes. With ethano bridge on the cyclobutadiene ring interaction with the diagonal bonds results in non-bonding AOs across the other diagonal having the opposite phase in the highest occupied (HO)MO. If the HOMO and LUMO are switched, bis-ethano-bridged tetrahedrane is formed. It is suggested that bis-ethano-bridged tetrahedrane is thermodynamically more stable than bis-ethano-bridged cyclobutadienes. While the reverse is true for unsubstituted cyclobutadienes. The ability of ethano bridges to reverse the usual order is because it causes the doubly-bonded carbons to pyramidalize.