Degree Type


Date of Award


Degree Name

Doctor of Philosophy




A method for the synthesis of thiophene-containing bicyclic prostaglandin analogues has been developed. Thienylpalladation of bicyclic olefins provides isolable (sigma)-palladium compounds which can be readily transformed into the desired bicylic prostaglandin analogues. Unfortunately, application of this approach to the synthesis of the analogous furans was unsuccessful. An approach has also been developed for the introduction of the trans-allylic alcohol side chain of a number of bicyclic prostaglandin analogues. The thiophene-containing bicyclic prostaglandin analogues could be hydrogenated to the completely saturated prostanoic acid analogues;A method has been developed for the synthesis of 7-oxa bicyclic prostaglandin analogues. Silver acetate assisted alkoxypalladation of norbornadienepalladium dichloride by t-butyl 6-hydroxyhexanoate affords an alkoxypalladium complex. Although this cannot be isolated, it can be carbonylated in methanol to afford either one of two diesters, which are useful intermediates in the synthesis of 7-oxa bicyclic and tricyclic prostaglandin analogues. These syntheses were completed by a sequence involving selective ester hydrolysis, Wittig olefination, and enone reduction. The synthesis of similar analogues through the reaction of an alkoxypalladium complex with a substituted lithium acetylide was unsuccessful;A general method for carbon-carbon bond formation between organomercurials and organocopper reagents has been discovered. Optimal conditions for the cross-coupling of a variety of aryl-, alkenyl-, and alkylmercurials with primary and secondary alkyl- and alkenylcuprate reagents have been examined. Lithium diorganocuprates and dilithium triorganocuprates give the best results with yields tending to decrease in the order methyl > vinyl > primary alkyl > secondary alkyl. With organomercurials, yields tend to decrease as follows: aryl > vinyl > primary alkyl > secondary alkyl. These reactions seem to proceed via mercury-copper transmetalation to generate a mixed organocopper species which then thermally or oxidatively eliminates the cross-coupled product. Consistent with this picture is the fact than an organic group originally attached to mercury can be readily added in conjugate fashion to (alpha),(beta)-unsaturated ketones, a reaction typical of an organocopper species.



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Douglas Robert Leach



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167 pages