New Modifications of the Biomass-derived and Now Abundant Homochiral Platform Molecule Levoglucosenone

Abstract

This thesis comprises seven scientific articles (Publications 1-7) and is preceded by an overview (synopsis) that contextualizes all of this published work. Publication 1 is a review article outlining emerging efforts concerned with the development of the four most abundant forms of biomass, namely cellulose, hemicellulose, lignin and chitin, as sustainable sources of commodity and fine chemicals. It summarizes the origins and properties of each of these biopolymers and then describes the extensive efforts to examine how each of these can be converted into platform molecules. Publication 2 is a research article that details studies on the manipulation of the enone moiety associated with the biomass-derived, homochiral and now abundant platform molecule levoglucosenone as well as that of it its pseudoenantiomer iso-levoglucosenone. Publication 3 is an invited review article that summarizes the development of the palladium-catalyzed Ullmann cross-coupling reaction within the Banwell Group. Specifically, it details the Group's extensive efforts to deploy this reaction in the synthesis of natural products and related bioactive compounds incorporating a range of heterocyclic substructures that are constructed through reductive cyclization of the initially formed cross coupling products. As such, Publication 3 serves to contextualize the research described in Publications 4 and 5. Publication 4 details methods for the reductive cyclisation of o-nitroarylated a,b-unsaturated carbonyl compounds arising from the palladium-catalyzed Ullmann cross-coupling reaction and that include products incorporating levoglucosenone-derived substructures. Complementary modes of reductive cyclisation could be realized by using either titanium trichloride/HCl or H2/Pd on C and so allowing for different heterocyclic systems to be obtained from a common substrate. Such processes significantly enhance the utility of the products available through the palladium-catalyzed Ullmann cross-coupling reaction. Publication 5 is a research article that details extensive experimental work involving the engagement of b-iodinated a,b-unsaturated carbonyl compounds in palladium-catalyzed Ullmann cross-couplings with o-halonitroarenes as well as the less reactive o-halobenzonitriles. The reductive cyclisation of the products of such reactions allows access to various heterocyclic frameworks including benzomorphans that, hitherto, have been inaccessible via such simple pathways. Publication 6 is a research article that details the deployment of a-iodinated derivatives of levoglucosenone and iso-levoglucosenone in palladium-catalyzed Ullmann cross-coupling reactions so as to form the corresponding nitropyridinylated derivatives. These products were themselves subjected to reductive cyclization reactions and so affording azaindole-annulated derivatives produced for the purposes of biological evaluation as antimicrobial and cytotoxic agents. Publication 7 is a research article that details the synthetic strategy for the production of polymers from levoglucosenone and iso-levoglucosenone derived monomers. Thus, the norbornene systems obtained through Diels-Alder reactions of these compounds with cyclopentadiene (CPD) undergo ring-opening metathesis polymerization (ROMP) in the presence of a range of ruthenium-based catalysts to produce polymers embodying both carbo- and hetero-cyclic motifs. Reduction of the carbonyl group in the Diels-Alder adduct derived from levoglucosenone and CPD provides the corresponding epimeric alcohols that can be etherified and the resulting ethers, including fluorine-containing ones, also yield well-controlled polymers via ROMP. As such, an efficient method has been devised for producing stereochemically and functionally diverse polymers from a renewable feedstock available at an industrial scale. The ROMP polymerizations are living ones as demonstrated by the facile preparation of block copolymers from the two Diels-Alder adducts.