Applications of α-Oxygenated Cyclopropanes in Organic Methodology

Chapter one firstly details the bonding and reactivity of cyclopropanes, and highlights these aspects in prior literature work. Furthermore the literature syntheses for the 1,3-oxazinone heterocycles, and how cyclopropanes have been exploited to prepare these compounds is shown. Chapter two explores physical and computational experiments to clarify whether the reaction of cyclopropyl acid chlorides and imines to form 1,3-oxazin-4-enones proceeds through a ketene or an iminium based mechanism. Research derived from previous Hawkins group explorations based on the generation of 1,3-oxazin-4-enones from cyclopropyl acid chlorides and imines was undertaken. Physical and computational experiments were performed to attempt to elucidate the mechanism of this reaction. Five physical experiments were undertaken, with four providing evidence in favour of an N-acyl iminium pathway predominating over a ketene pathway. The computational experiments generated ground state and first-order saddle point geometries of intermediates and transition states respectively, allowing for the generation of an energetic pathway along both the N-acyl iminium and ketene pathway. This data found the lower energy pathway was that for the N-acyl iminium pathway, and between physical and computational data it was concluded that it was highly likely that the reaction proceeded via an N-acyl iminium intermediate. Chapter three details the preparation of cyclopropyl carbinols through a reductive-ring opening 1,3-oxazin-4-enones utilising lithium aluminium hydride in moderate to good yields. Alongside the mechanistic work, reactions to derivatize the 1,3-oxazin-4-enones were undertaken. Initial attempts to reduce these parent heterocycles to their saturated 1,3-oxazine counterparts instead led to the production of cyclopropyl carbinols through a reductive ring-opening reaction. The scope of this reaction was explored, and 17 novel cyclopropyl carbinols were prepared in moderate to good yields. Previous literature surrounding cyclopropyl carbinols found limited scope for their preparation but broad application for their derivatization, and it was expected that this work could allow for expansions into previous methodology. Chapter 4 covers the scope of a hypervalent-iodine mediated formation of bicyclic cyclopropyl ketals, as well as the derivatization of these compounds Finally, a method for the preparation of novel bicyclic cyclopropyl hemi-ketals from 1-carbonyl-2-vinyl cyclopropanes was established using a (diacetoxyiodo)benzene and sodium iodide mixture. The scope of this reaction was explored, with 12 novel cyclopropyl hemi-ketals prepared in moderate to good yields. Alongside these, methods for the preparation of a bicyclic cyclopropyl lactone and a dihydrofuran were found utilising similar reaction conditions. Modification of the hemi-ketals was to afford dihydrofurans, bicyclic cyclopropyl ketals, bicyclic cyclopropyl ethers, bicyclic cyclopropyl lactams, and tetracyclic quinolinocyclopropafurans is also reported. Chapter 5 covers the remaining work to be undertaken in each of these projects, as well as highlighting potential future work. Finally, chapter 6 describes the experimental procedures used