The interplay of structure and reactivity on a ring closing metathesis reaction

This Thesis describes investigations of how structure affects a cyclooctannulation of a difluorinated diene via ruthenium-catalysed ring closing metathesis (RCM). The study originated in attempts to optimise these reactions towards the synthesis of novel difluorinated analogues of sugars.;A range of difluorinated dienes have been synthesised in order to study the effects of allylic protecting group on cyclisation efficiency, using the CF2 group as a probe to reaction outcomes via 19F NMR. We identified a 102 fold difference in cyclisation efficiency depending on which allylic protecting group was used. However, kinetic studies have shown us that allylic protecting groups have only a moderate effect on cyclisation rate. Kinetic studies have also shown us that the cyclisation is affected by the presence of gem-dialkyl groups, which accelerate the rate---an effect which has not been quantified for the formation of medium rings by RCM previously.;1H NMR kinetics has enabled the identification of the most significant catalytic species on the reaction timescale, including identification of catalytic decomposition products. This has led to the development of a kinetic data model to which all kinetic data were fitted, using simulation software, and has allowed a deeper analysis and understanding of how olefin structure affects reactivity in RCM.;Based on the kinetic data, RCM substrates, which prolong catalytic lifetime and simplify reaction kinetics have been synthesised and examined. In addition to this, the effects of reaction solvent, temperature, catalyst and catalyst loading on the cyclisation rate have been studied in order to identify the optimum conditions for synthesis of the desired difluorinated cyclooctenones

Quality control in the decentralized production of biosand filters: a pilot workshop in Zambia

The locally produced, concrete biosand filter is a household water treatment option for improving water quality. As of December 2015, over 830,000 biosand filters had been implemented in 60 countries around the world. Local, decentralized production is an advantage of the technology but also creates challenges with quality control. This paper describes the development, piloting and evaluation of a quality control workshop in Zambia. The overall reaction to the workshop was positive. Based on results from the pilot, CAWST will revise the workshop to better achieve learning outcomes and improve the efficacy of the workshop

Selected Substituent Effects on the Rate and Efficiency of Formation of an Eight-Membered Ring by RCM

Studies of a range of reactions forming cyclooctenones highlight a discrepancy between cyclization rate and cyclization efficiency. Cyclization rates change modestly as the oxygen function at the allylic position is varied, and increase upon gem-dimethylation. Cyclization efficiency has also been quantified for four substrates, revealing a range of effective molarities (EMs) of 2 orders of magnitude that are substituent dependent. The most efficient cyclization appears to result from suppression of the cross-metathesis pathway through which oligomerization begins, rather than from a particularly rapid cyclization reaction. In the presence of a Ti(IV) cocatalyst, diene monomers transform smoothly to eight-membered-ring products without the intermediacy of dimers or other oligomers, indicating that the cyclizations are kinetically and not thermodynamically controlled. The gem-dialkyl effect is also shown to be kinetic

Selected Substituent Effects on the Rate and Efficiency of Formation of an Eight-Membered Ring by RCM

Studies of a range of reactions forming cyclooctenones highlight a discrepancy between cyclization rate and cyclization efficiency. Cyclization rates change modestly as the oxygen function at the allylic position is varied, and increase upon gem-dimethylation. Cyclization efficiency has also been quantified for four substrates, revealing a range of effective molarities (EMs) of 2 orders of magnitude that are substituent dependent. The most efficient cyclization appears to result from suppression of the cross-metathesis pathway through which oligomerization begins, rather than from a particularly rapid cyclization reaction. In the presence of a Ti(IV) cocatalyst, diene monomers transform smoothly to eight-membered-ring products without the intermediacy of dimers or other oligomers, indicating that the cyclizations are kinetically and not thermodynamically controlled. The gem-dialkyl effect is also shown to be kinetic

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate

Total Syntheses of Conformationally Locked Difluorinated Pentopyranose Analogues and a Pentopyranosyl Phosphate Mimetic

Trifluoroethanol has been elaborated, via a telescoped sequence involving a metalated difluoroenol, a difluoroallylic alcohol, [2,3]-Wittig rearrangement, and ultimately an RCM reaction and requiring minimal intermediate purification, to a number of cyclooctenone intermediates. Epoxidation of these intermediates followed by transannular ring opening or dihydroxylation, then transannular hemiacetalization delivers novel bicyclic analogues of pentopyranoses, which were elaborated (in one case) to an analogue of a glycosyl phosphate