This thesis explores the feasibility of preparing chiral enamines from dihydrolevoglucosenone (DHLGO), a biorenewable chiral synthon easily accessible from cellulose containing waste materials, and their potential applications in organic synthesis. A particular focus was to use these enamines as intermediates in α-functionalisations of the carbonyl group, which has resulted in five separate manuscripts, two of which have already been published in international peer reviewed scientific journals.1,2 Each manuscript constitutes a separate chapter in this thesis.
The first manuscript (Chapter 2) is centred around the first synthesis of enamines from DHLGO and their reactivity with a selected set of electrophiles. Two stable crystalline enamines prepared from morpholine and piperidine were isolated in 89% and 79% yields, respectively. Their reactions with ketenes, isocyanates and isothiocyanates gave access to novel chiral cyclobutanones, amides and thioamides. This laid the foundation for the second study (Chapter 3), in which the utility of the enamines in aldol condensations with aliphatic aldehydes was investigated. Although initial attempts resulted in relatively low yields, it was discovered that catalytic amounts of piperidine generating the enamine species in-situ, from which α-alkylidene derivatives could be accessed in good yields. Subsequent Baeyer-Villiger oxidations resulted in the first reported synthesis of the bioactive natural products (+)-majoranolide and (+)-majoranolide B. The manuscript in Chapter 4 describes aromatic analogues of (+)-majoranolide formed from DHLGO via aldol reactions, and the materials were screened for anticancer and antimicrobial activity.
Utilizing the enamines presented in Chapter 2, a series of novel and known chiral 1,2-aminoalcohols were prepared (Chapter 5). The synthesis of the novel 1,2-aminoalcohols was achieved by developing amine mediated α-amination strategies for DHLGO and its derivatives, and using αoxidation/reductive amination to prepare regioisomeric materials. The 1,2-aminoalcohol products were investigated as organocatalysts in aldol additions. During the preparation of these organocatalysts, a novel and efficient approach for the α-arylation of DHLGO via halogenated enamines was co-developed with another researcher and the results are presented in Chapter 6.