Some novel aspects of the chemistry of thiophens

Abstract

The research described in this thesis is prefaced by an introductory review on sulfur ylide chemistry. The initial objective of this project was the development of efficient syntheses of the commercially important compounds 2-thienylacetic acid and 3-thienylmalonic acid and several approaches to these were examined with little success. Reports that the addition of diazoacetic ester to thiophen gave a cyclopropane derivative which, on treatment under acid conditions, gave a 3-substituted thiophen derivative, prompted us to examine this reaction with a view to the preparation of 3- hienylmalonate. The reactions of diazomalonate with thiophen under traditional cyclopropane- orming conditions gave low yields of 2-thienylmalonate. However when this reaction was carried out at room temperature in the presence of rhodium (II) acetate a quantitative formation of the ylide 57 (R-^,R2 ,Rg »R^ = H; R5,R6 = C02Me) occurred. An X-ray crystal structure determination helped to confirm the structure of this stable crystalline solid. 57 Several ylides of the type (57) were prepared in high yield using alkyl- or halogenothiophens but thiophens bearing substituents with a -M effect failed to produce ylides. Reactions with diazo compounds other than diazomalonic esters failed to produce ylides, the products being 2-substituted thiophens, cyclopropanated thiophens, or a mixture of the two. Thermolyses of the ylides yielded 2-substituted thiophens and other products derived, apparently, from intra molecular nucleophilic rearrangement of the ylides. It is considered likely, in view of these rearrangements, that the reactions of all diazo compounds with thiophens proceed via ylides of the type (57) and that all the products are derived from these, often unstable, intermediates. Thermolyses of the ylides in the presence of transition metal salts proceed by an entirely different mechanism, the intermediacy of bis(methoxycarbonyl)carbene, or a metal- tabilized carbenoid species, being likely. This carbenoid has been trapped by cyclohexene and its formation under the above conditions has proved to be extremely useful from a synthetic viewpoint as illustrated by its use in the cyclopropanation of unactivated olefins, its reaction with activated arenes to form arylmalonates, and its insertion into acidic X-H bonds. A further interesting reaction of this intermediate is its ability to deoxygenate epoxides in a stereospecific manner, a reaction thought to proceed through an intermediate oxonium ylide