This thesis presents an investigation into the chemistry of 6 substituted 5, 6-dihydro-a-pyrone compounds. A comprehensive review of these compounds was published in 1989 and the subsequent literature is covered in an updated review presented below. Eight 6-substituted 5,6-dihydro-a-pyrone metabolites from three different South African plant species Cryptocarya latijolia, Syncolostemon densiflorus, and Syncolostemon argenteus have been the subject of structural and stereochemical investigations. The absolute stereochemistry of the known compound "triacetate" from C. latijolia has been established as 6R-[2R,4S,6S-(triacetyloxy)heptylJ-5,6-dihydro-2H-pyran-2-one (74) using CD and acetonide formation with subsequent application of the modified Moshers method. The absolute stereochemistry of the related metabolite "diacetate", also from C. latijolia, has been assigned as 6R-[2S,4S-diacetyloxypentylJ-5,6-dihydro-2H-pyran-2-one (76). In addition, the outstanding stereochemistry at C-5' in syndenolide, from S. densiflorus, followed from conversion to its diacetonide and subsequent NMR analysis. Syndenolide is therefore 6R-[5S-(acetoxy)-IR,2R,3S-(trihydroxy)-heptylJ-5,6- dihydro-2H -pyran-2-one. The genus Syncolostemon has proved to be a rich source of a-pyrone compounds and the chemistry of S. argenteus, not investigated previously, was examined as part of an ongoing search for new 5,6-dihydro-a-pyrones. The study yielded five new a-pyrone natural products, synargentolide A-E. The structure of synargentolide A (82) has been assigned as 6R[4R,5R,6S-triacetyloxy-lE-heptenylJ-5,6-dihydro-2H-pyran-2-one using CD and NMR techniques. The structures of synargentolide B (87), C (92) and E (94) also followed from a detailed NMR analysis and the stereochemistry tentatively assigned based on CD and NMR data. Synargentolide D (93) was thermally unstable, and a paucity of material prevented stereochemical investigations, however the structure was determined from initial NMR analysis. The marine molluscs of the genus Siphonaria have only become the subject of chemical studies in the last fifteen years. These molluscs characteristically produce polypropionate type natural products. A review of Siphonarian polypropionate metabolites containing a pyrone functionality is presented. Examination of an endemic South African species Siphonaria serrata yielded one novel polypropionate metabolite containing a ),-pyrone functionality, siserrone A (131). The structure of this compound was unambiguously established using standard NMR experiments. The relative stereochemisty of the hemi-ketal moiety was assigned from a careful analysis of the ROESY NMR spectrum and the stereochemisty of the acyclic portion determined from a comparison of the 13C and 'H NMR data of a degradation product with the corresponding data of a synthetic compound. It was also established that the modified Moshers method could not be used to determine the absolute stereochemistry of the secondary hydroxy I substituent at C-11. The absolute stereochemistry of 131 was thus assigned in accordance with the proven stereochemistry of Siphonarian metabolites.

Some of the evidence supporting the olefin-like character of cyclopropyl groups, the double-bond assisted solvolysis of 7-norbornenyl derivatives and the ability of the cyclopropyl group to anchimerically assist ionization is reviewed. With regard to the high rate of solvolysis of 7-norbornenyl esters, the similarity of olefins and cyclopropyl groups and the steric features of the tricyclo [3.2.1.0 ²'⁴] octane ring system, a solvolytic study of tricyclo [3.2.1.0²'⁴] oct-8-yl derivatives was undertaken to determine whether a suitably oriented cyclopropyl group can also provide a large anchimeric assistance to ionization. The synthesis of the four isomeric tricyclo [3.2.1.0²'⁴] octan- 8-ols (II-OH, VIII-OH, XVI-OH and XVII-OH) is described. The cuprous chloride-catalyzed addition of diazomethane to anti-7-norbornenol gave pure exo-anti-tricyclo [3.2.1.0²'⁴] octan-8-ol (II-OH). Addition of diazomethane to 7,7-dimethoxynorbornene gave exo-8,8-dimethoxytricyclo [3.2.1.0²'⁴] octane (Vl) which was hydrolyzed to the corresponding ketone (VII) with acid. Reduction of the exo ketone afforded pure exo-syn-tricyclo [3.2.1.0²'⁴] octan-8-ol (VIII-OH). Attempts to prepare endo methylene adducts from norbornenes failed, although they were obtained from norbornadienes. The endo-tricyclo [3.2.1.0²'⁴] octan-8-ols were therefore prepared by a different route. Reaction' of 5,5-dimethoxy-l,2,3,'f-tetrachlorocyclopentadiene with cyclo- propene gave the endo Diels-Alder adduct (Xii). Dechlorination of this compound with metallic sodium, followed by catalytic hydrogenation, gave endo-8,8-dimethoxytricyclo [3.2.1.0²'⁴] octane (XIV). This ketal, upon acid hydrolysis, afforded the endo ketone (XV) which was reduced by a variety of reagents to give mixtures of the two endo alcohols. Preparative gas-liquid phase chromatography (glpc) gave pure samples of endo-syn and endo-anti-tricyclo [3.2.1.0²'⁴] octan-8-ols (XVI-OH and XVII-OH). Acetolysis of the p-bromobenzenesulfonates (brosylates) of the endo-syn and exo-syn alcohols in acetic acid and hydrolysis of the p-nitro- benzoates of the endo-anti alcohol and of anti-T-norbornenol in 70% aqueous dioxane gave relative rates of ionization of 37, 10⁴, 10¹² and 10⁹, respectively, compared to the solvolytic rate of a 7-norbornyl derivative at 100°. The exo-anti derivative (II-OBs) had previously been shown to have a relative solvolytic rate of 1.65 under these conditions. Acetolysis of the exo-syn and endo-syn brosylates gave rise to mixtures of entirely rearranged products which were not identified. Hydrolysis of the endo-anti p-nitrobenzoate in 70% aqueous dioxane gave rise only to endo-tricyclo [5-1.0.0⁴'⁸] oct-3-yi (XVIIl) products. The kinetic and product study data are consistent with the proposal that the endo-anti derivatives ionize to the 2,4-ethanotrishomocyclopropenyl cation. The stereochemistry of the reactions by which the tricycle [3.2.1.0²'⁴] octane ring system is formed, the effect of the stereochemistry of this ring system on the spectral characteristics of its derivatives and the mechanistic implications of the kinetic and product study data are discussed. [Symbols and illustrations omitted]. / Science, Faculty of / Chemistry, Department of / Graduate

Supervisor: Dr. R.E. Pincock In order to attempt to define more rigourously the geometric requirements of bridgehead free radicals, two t-butyl peresters of bridgehead acids are prepared — t-butyl adamantane-1-percarboxylate and t-butyl norbornane-1-percarboxylate. The decompositions of these peresters are examined, the rates determined, and the activation parameters for the decompositions calculated. Evidence is presented which suggests that the decomposition of t-butyl adamantane-1-percarboxylate proceeds via a concerted mechanism, splitting out CO₂ and producing the bridgehead free radical. An enthalpy of activation of 30.5 kcal./mole and an entropy of activation of 13 cal./deg. are determined. Similar evidence is presented which indicates that t-butyl norbornane-1-percarboxylate also decomposes via the concerted mechanism. The enthalpy of activation for this decomposition is found to be 32.2 kcal./mole and the entropy of activation found to be -3.6 cal./deg. The results obtained here are compared to those of other workers, and the inference that the entropy of activation plays a major role in determining rates of such decompositions is made. A synthetic pathway to another bridgehead perester, t-butyl bicyclo[2,2,2]octane-l-percarboxylate is explored, and a new and more practicable synthesis of bicyclo[2,2,2]octane-l-carboxylic acid presented. A comparison of bridgehead free radicals to bridgehead carbonium ions is made, and other evidence pertinent to the stereochemistry of bridgehead free radicals is discussed. / Science, Faculty of / Chemistry, Department of / Graduate

The crystal and molecular structure of cacodylic acid, (CH₃)₂AsO.OH, has been determined by X-ray diffraction of a single crystal. The crystals belong to the triclinic system with a = 6.53, b = 6.82, c = 6.61 Å, α = 77°30', β = 78°45', γ = 55°9', z = 2, space group P1̅. The structure was determined from visual intensity data by Patterson and Fourier methods, and the positional and anisotropic thermal parameters were refined by least-squares. The final discrepancy factor is 0.149 for 806 observed reflections. The structure consists of centrosymmetrical, hydrogen-bonded dimers, with 0-H...0 distances of 2.57Å, the arsenic atoms having a tetrahedral configuration with bond angles in the range 106° - 115°. Crystals of antimony triiodide, SbI₃, are rhombohedral with a[subscript H] = 7.48 Å, C[subscript H] = 20.90 Å, z = 6, space group R3̅. The structure was determined from h0.ℓ Patterson, Fourier and difference projections, the final discrepancy factor being 0.131. The antimony atoms are significantly displaced from the centres of iodine octahedra, and have three near neighbour iodine atoms at 2.868 ± 0.010 Å, with I-Sb-I = 95.8 ± 0.3°, and three further off at 3.316 ± 0,010 Å, The structure is thus intermediate between that of a molecular crystal, as in Asl₃, and an ionic arrangement. Crystals of Bil₃ have a[subscript H] = 7.52 Å, c[subscript H] = 20.72 Å. Comparison of measured and calculated powder intensities suggests that the bismuth atom is situated at the centre of an iodine octahedron, so that the structure is probably largely ionic. Lone-pair steric effects, as well as changes in bonding character, are thought responsible for the differences in the crystal structures of Asl₃, Sbl₃ and Bil₃. / Science, Faculty of / Chemistry, Department of / Graduate

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