The synthesis of tri- and tetrasubstituted cyclopropanes from 3-aryl-substituted levoglucosenones (LGO) has been developed. In contrast to the unstabilised ylide dimethylsulfonium methylide which gives epoxides from LGO via 1,2-addition, we have found that the soft nucleophile dimethylsulfoxonium methylide affords cyclopropanes in moderate yields from LGO and in excellent yields and stereoselectivity with 3-aryl LGO derivatives. The use of 1,1,3,3-tetramethylguanidine as base in DMSO to generate the ylide provided the best yields and shortest reaction times. Ester stabilised sulfonium ylides could also be used to generate tetrasubstituted cyclopropane derivatives. One of the products was converted into a cyclopropyl lactone via Baeyer-Villiger oxidation to demonstrate the utility of applying cyclopropanation chemistry to LGO.

Efficient conditions have been developed for the diastereoselective aziridination of the biomass pyrolysis product (−)-levoglucosenone, via the reaction of primary aliphatic amines with 3-iodolevoglucosenone. In contrast to the reactions of aliphatic amines, the use of 4-methoxyaniline resulted in an aza-Michael-initiated dimerisation reaction, and 1,3-diphenylurea gave a 2-imidazolidinone. The aziridine products were transformed using the aza-Wharton reaction, affording novel sulfonamide and amine-substituted 6,8-dioxabicyclo[3.2.1]oct-3-enes with potential as sp³-rich chiral scaffolds.

The cellulose-derived species, levoglucosenone (LGO), has only recently become available in large quantities although it was first identified in 1973. The increased availability of this chiral, biorenewable starting material means that its potential uses in synthesis can be examined. Therefore, this thesis is aimed at further expanding the repertoire of reactions known for LGO and to synthesise several targets via these reactions.

Chapter 2 details the microwave-optimised Suzuki-Miyaura arylation of 3-iodolevoglucosenone. Microwave irradiation, compared to conventional heating, provided greatly improved reaction times while giving similar yields. This development allowed for rapid access to a range of 3-aryl derivatives of LGO.

The 3-aryl derivatives were used to explore Johnson-Corey-Chaykovsky cyclopropanation in Chapter 3. The use of an unstabilised sulfoxonium ylide and 1,1,3,3-tetramethylguanadine (TMG) in dimethyl sulfoxide afforded a range of 1,2-trisubstituted cyclopropane derivatives in excellent yield. Furthermore, a range of 1,2,3-tetrasubstituted cyclopropane derivatives were produced in high yield using stabilised sulfonium ylides and TMG in tetrahydrofuran. Cyclopropanation reactions proceeded with high diastereoselectivity due to the preferential approach of the ylide to the exo-face of the bicyclic ring system

In Chapter 4 two known central nervous system bioactive compounds were synthesised from two different cyclopropane derivatives, prepared in Chapter 3. The enantioselective synthetic pathways involved Baeyer-Villiger oxidation, butyrolactone opening and oxidative cleavage to dehomologate the chain giving an aldehyde that was then reductively aminated. The methods developed to access these bioactive compounds have a comparable number of steps to the previously published procedures.

The incorporation of a benzyl group to the α-carbon of dihydrolevoglucosenone was explored in Chapter 5. The most efficient method of producing an α-benzyl derivative of dihydrolevoglucosenone was determined to be via an aldol condensation. The scope of the reaction was explored using several benzaldehydes to give a range of benzylidenes. Subsequently, the unsubstituted benzylidene was then reduced to afford an α-benzyl derivative and further transformed into enantiomerically pure (3R,5S)-3-benzyl-5-(hydroxymethyl)dihydrofuran-2(3H)-one, which is an intermediate in the synthesis of the commercial protease inhibitor, indinavir.

Chapter 6 explored the incorporation of nitrogen groups onto the levoglucosenone scaffold through aza-Michael addition and aziridination reactions. Aza-Michael addition to levoglucosenone was possible with aliphatic amines under aqueous conditions, however, to avoid product decomposition the β-aminoketones were reduced to alcohols in situ. The β-amino alcohol derivatives were isolated in moderate to excellent yield with varying diastereomer ratios, which were dependent on the amine group. Aziridination of 3-iodolevoglucosenone was achieved with several primary amines to produce aziridine derivatives in moderate to excellent yield. These aziridine derivatives were further transformed via ring-opening aza-Wharton reactions to afford allylic amines in moderate to high yields. The nitrogen containing scaffolds reported in this chapter could be utilised in the development of novel, bioactive aminoglycosides.

Lastly, Chapter 7 details the unprecedented direct Weitz-Scheffer epoxidation of LGO and 3-aryl derivatives. Using anhydrous tert-butyl hydroperoxide and the non-nucleophilic base 1,8- diazabicyclo[5.4.0]undec-7-ene, the epoxide derivatives were afforded with short reactions times and in good to excellent yield. The key to this chemistry was the finding that water had to be excluded due to the formation of hemiacetals. The epoxides were subsequently subjected to Wharton conditions to produce allylic alcohols and then oxidised to afford the constitutional isomers of LGO and the 3-aryl derivatives in good yields. These pseudo-isomers were therefore accessible from the initial enones in three simple steps and allow for further investigation of their reactivity and possible future application in targeted synthesis.

Chiral amines are highly coveted within the fine‐chemical industry and sustainable synthetic methodologies for their production are of great value. By harnessing the chirality present in cellulose‐derived (–)‐levoglucosenone (LGO), several bio‐based sp³‐rich amines containing up to four chiral centres have been readily prepared under aqueous conditions without using any catalysts, ligands, auxiliaries or resolutions.

Lignocellulosic biomass pyrolysis with acid catalysis selectively produces the useful chiral synthon 6,8-dioxabicyclo[3.2.1]oct-2-ene-4-one ((-)-levoglucosenone,LGO). In this report, LGO was used to prepare (3R,5S)-3-benzyl-5-(hydroxymethyl)-4,5-dihydrofuran-2(3H)-one, which is an intermediate used in the construction of antivirals including the protease inhibitor indinavir. To achieve the synthesis, the hydrogenated derivative of LGO was functionalised using aldol chemistry and various aromatic aldehydes were used to show the scope of the reaction. Choice of base affected reaction times and the best yields were obtained using 1,1,3,3-tetramethylguanidine. Hydrogenation of the α-benzylidene-substituted bicyclic system afforded a 4:3 equatorial/axial mixture of isomers, which was equilibrated to a 97:3 mixture under basic conditions. Subsequent Baeyer-Villiger reaction afforded the target lactone in 57 % overall yield for four steps,a route that avoids the protection and strong base required in the traditional approach. The aldol route is contrasted with the α-alkylation and a Baylis-Hillman approach that also both start with LGO.

High-yielding epoxidation conditions for the cellulose pyrolysis product (−)-levoglucosenone (LGO) and 3-aryl derivatives of LGO have been developed. The reaction of LGO with hydrogen peroxide/base is known to give a Baeyer-Villiger reaction, however, it was found that the reactions of LGO or derivatives with tert-butylhydroperoxide/base affords solely epoxides through the Weitz-Scheffer reaction. A critical parameter in the successful isolation of the epoxide from LGO was to avoid all contact with water or alcohols during the reaction and workup. The epoxide products were reacted under Wharton conditions affording allylic alcohols and subsequent oxidation led to isolevoglucosenone or 3-arylisolevoglucosenone derivatives. Previously unreported reactions on isolevoglucosenone were then investigated.

Infrared Spectroscopy data relating to Novel Transformations and Applications of the Biomass Pyrolysis Product Levoglucosenone