This thesis by publication includes an introductory chapter and a comprehensive literature review that together provide the research context and outline the aims and significance of the work on biomassderived chiral synthons. The subsequent chapters present a series of research articles describing the development of new transformations of the biomass derivatives levoglucosenone (LGO) and Cyrene.
Chapter 1 provides an overview of existing literature about LGO and Cyrene, as well as general transformations of enamines. Chapter 2 describes the intermolecular enamine-Mizoroki–Heck reaction of enamines derived from Cyrene, to yield a series of arylated tertiary amines in good yields and diastereoselectivity. Chapter 3 details a ring-expansion strategy for Cyrene using gemdihalocyclopropane intermediates, enabling controlled formation of ring-expanded alkenyl halides and homologated levoglucosenone. Chapter 4 investigates a one-carbon difluorocyclopropanation/ringexpansion sequence to access fluorinated analogues of Cyrene. In Chapter 5, a traceless methylene insertion into Cyrene with ethyl diazoacetate was achieved, which was further functionalised, demonstrating scalable access to chiral C7 synthons.
Chapter 6 reports the synthesis of feeding modulators 3-deoxy-D-arabino- and D-ribono-1,4-lactones from Cyrene via a diastereoselective bromination using an enamine. Installation of oxygen nucleophiles was achieved, with stereochemical outcomes rationalised by oxirane intermediates and rearrangements. Chapter 7 describes the preparation of halogenated butyrolactones from levoglucosenone, affording fluorinated, chlorinated, and brominated dideoxyribonolactones.
Chapter 8 investigates the skeletal rearrangement of the 6,8-dioxabicyclo[3.2.1]octan-4-ol ring system via either SOCl₂/pyridine or Appel conditions, providing access to novel bicyclic ring-systems. In Chapter 9, an acid-catalyzed redox isomerization of substituted 6,8-dioxabicyclo[3.2.1]octan-4-ols yielded chiral pyranones, while kinetic isotope effects studies allowed mechanistic insights into the formation of LGO during pyrolysis. Chapter 10 details the synthesis of two bioactive compounds from LGO through Suzuki-Miyaura coupling, cyclopropanation, and oxidation, describing alternative pathways for the synthesis of a σ-receptor ligand. Chapter 11 develops a N-heterocyclic carbene switchable mechanism for the direct arylation of alkyl and aryl thiols with aryl iodides via benzyne and radical pathways.
A concluding chapter synthesises the findings from these publications, highlighting their collective contribution to advancing biomass-derived chemical synthesis and outlining future research directions.