Abstract
AbstractChapter 1 of this thesis details a novel process in accessing bicyclic systems possessing a cyclopropane ring. Specifically, when ester 76 was treated with lithium diisopropylamide (LDA) followed by a doubly activated Michael acceptor (i.e. 2-cyano-2-cycloalkenones), a tandem process involving a 1,4-addition followed by an intramolecular SN2 displacement reaction ensues to furnish bicyclic systems 80a and 80b, the individual reative stereochemistry of which were determined by X-ray crystallography and/or detailed analysis of the coupling constant patterns found in their respective 1H-NMR spectra.Chapter 2 expounds upon our investigation towards the construction of highly congested cyclohexenes via the Diels-Alder cycloaddition reaction. Towards this end, various glycols (i.e. 141) were mono-protected to give compounds 145-148 which were individually oxidized using pyridinium chlorochromate (PCC) to furnish aldehydes 149-152. The desired dienophiles 154-157 were then achieved by treating aldehydes 149-152 individually with malonate 153 under Knoevenagel conditions. Olefins 154-157 were found to be highly dienophilic and furnished the corresponding individual Diels-Alder cycloadducts 158-169 readily. The nitrile moiety present in the resulting cycloadducts could be replaced by an alkyl group using a reductive alkylation process mediated by lithium naphthalenide (LN) developed in our laboratories to give highly congested cyclohexenes 170-178. It was also discovered that, for cycloadducts generated starting from ethylene glycol and upon unmasking the hydroxyl by treatment with tetrabutylammonium fluoride (TBAF), □-lactones 179-181 was obtained apparently due to spontaneous cyclization of the ensuing alkoxide onto the adjacent methyl ester. The resulting □-lactones 179-181 were identified to possess a cis-ring junction as per extensive n.O.e. experiments. For cycloadducts 170-178 where n > 1, the TBAF mediated deprotection proceeded uneventfully to furnish alcohols 182-184. Subsequent oxidation using pyridinium dichromate (PDC) followed by esterification yielded diesters 189-191 which were then exposed to Dieckmann condensation reaction conditions to yield bicyclic keto esters 192-195.Chapter 2 extends the Diels-Alder cycloaddition study by the incorporation of a chiral auxiliary on the ester present in the dienophile. Towards this end, optically active menthol derivative 205, arrived at starting from (R)-(+)-pulegone (i.e. 196), was acylated to give optically active ester 197. Knoevenagel reaction with ester 197 and a series of carbonyl containing building blocks then furnished the desired optically active dienophile 198 which was indeed found to be dienophilic and readily furnished cycloadducts 199.