Keto acid phosphoranes: structure, synthesis, and bromolactonisation
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
This thesis examines the structure, synthesis, and bromolactonisation of keto acid phosphoranes. Chapter One discusses the structure and the intra- and intermolecular hydrogen bonding preferences of a number of keto acid phosphoranes. The mode of hydrogen bonding was determined by X-ray crystallography, infrared spectroscopy, and Raman spectroscopy. 1- ethoxycarbonyl-5-carboxy-2-oxopentylidenetriphenylphosphorane 1.8, is shown to exist as a carboxyl to ketone catemer, and a unique sixteen membered acid carboxyl to ketone intermolecular dimer, in the solid state. Chapter Two introduces a new synthesis of halo enol lactones via a modified SCOOPY reaction on a keto acid phosphorane. A mechanistic investigation of this bromolactonisation reaction is reported, in particular, the participation of phosphonium salts and allenes in the mechanism is discussed. The synthesis of keto acid phosphoranes via a Wittig Anhydride Carbonyl Olefination reaction, and the reaction of acid chlorides with a stabilised ylide, is also described. The acid chloride reaction was shown, by low temperature ¹H, ¹³C, and ³¹P NMR spectroscopy, to proceed via an initial 0-acylphosphonium salt that readily rearranges to a C-acylphosphonium salt. The synthesis of the five-membered E- and Z-succinic bromo enol lactones, and the X-ray crystal structure of ethyl bromo(Z-5-oxotetrahydrofuran-2-ylidene)acetate 2.34, is reported. Chapter Three extends the bromolactonisation reaction to the six membered glutaric bromo enol lactones. The synthesis of E- and Z-glutaric, 3-methylglutaric, and the 3,3-dimethylglutaric bromo enol lactones are reported. Chapter Four further extends the bromolactonisation reaction to the five-membered aromatic E- and Z-phthalic bromo enol lactones. The reaction of phthalic anhydride with the bromo ylide 2.31 forms the E- and Z-phthalic bromo enol lactones 4.25 and 4.26, in the same stereoisomeric ratio as the bromolactonisation reaction. The X-ray crystal structure of ethyl bromo-(Z-3-oxo-1,3-dihydroisobenzofuran-1-ylidene)acetate 4.26 is reported. The reactivity of the keto acid phosphoranes was shown to be increased by 3-methyl aromatic substitution, and decreased by 3-nitro aromatic substitution. Chapter Five deals with the application of keto acid phosphoranes to the synthesis of amino acid analogues. The bromolactonisation reaction is extended to include amine and aromatic substituents. The synthesis of E-and Z-3-phenylglutaric bromo enol lactones is reported. The synthesis of bromo enol lactones from asymmetric phenylsuccinic, acetyl protected aspartic, and benzyloxycarbonyl protected aspartic derived keto acid phosphoranes is discussed. A versatile synthesis of β-Cbz-aspartic bromo enol lactones, via protection of the α-carboxylic acid of Cbz-L-aspartic acid, is reported.