Procedures for collecting data on a diffractometer equipped with an area detector from samples held within the diamond anvil cell have been developed. The cell construction limits access to reciprocal space and leads to contamination of the diffraction patterns, leading to problems in indexing, data processing and refinement; these effects have been investigated and some strategies for overcoming these are described. Compression studies of the amino acid glycine show the formation of a new polymorph below 8 kbar via a single crystal – single crystal phase transition from the known β-phase of glycine. The formation of this new polymorph can be rationalised on topological grounds by changes in the packing of the molecules to a more favourable body centred cubic based arrangement. γ-glycine was found to undergo a phase transition, characterised using powder diffraction at high pressure. The behaviour is consistent with the formation of δ-glycine. The crystal structure of the amino acid l-alanine is stable to the effects of pressure to at least 70 kbar. The hydrogen-bonding network undergoes significant distortion; this distortion can be explained by the structure adopting a more body centred cubic packing arrangement with increasing pressure. Crystal growth at high pressure from liquid resulted in the formation of new polymorphs of formamide and pyridine. Growth of crystals of the N-methylated analogues of formamide, N-methyl formamide and N,N-dimethyl formamide, did not. The structure of the high pressure polymorph of formamide formed at 4.4 kbar is closely related to the previously known phase. At 10.8 kbar pyridine crystallises in a much simpler structure than that observed at low temperature, matching the structure observed for the perdeuterated molecule. A novel hemi-hydrate of piperidine is observed when grown from liquid at 3.1 kbar.

A review of phosphorane chemistry is presented. From a range of spirophosphoranes the relative apicophilicity of sulphur and oxygen containing ligands was determined. The conclusion reached was that the relative apicophilicities of ethylthio, ethoxy and trimethylsiloxy were similar. The N-chlorodi-isopropylamine method for the preparation of spirophosphoranes was developed, enabling the preparation of various unsymmetrical phosphoranes, from which the relative apicophilicities of phenoxy and phenylthio groups were determined. The preparation of spirophosphoranes from phosphetans was shown to go with retention of configuration at phosphorus. The interconversion of the cis and trans spirophosphoranes prepared from phenyl and benzylphosphetans was followed kinetically, and from this study the phenyl group was shown to be more apicophilic than the benzyl group. Cyclic and acyclic phosphites were reacted with acrylic acid. In the case of cyclic phosphites spirophosphoranes were prepared from which the relative apicophilicity of the phenyl group was determined. A series of spirophosphoranes was prepared containing a 4,4,5,5-tetramethyl-1,3,2-dioxaphospholan ring. On thermolysis these were found to give 2,3-dimethyl-butadiene as the major component and some t-butyl methyl ketone. From a series of hexafluorobiacetyl and tetrachloro-o-benzoquinone adducts the relative apicophilicities of chlorine, cyanide, isocyanate and isothiocyanate were determined. It was shown that the cyanide was more apicophilic than chlorine, whilst the isocyanate and isothiocyanate were found to have a similar apicophilicity to chlorine. The first pentaco-ordinate phosphorane containing an azide ligand was prepared by direct substitution of a chlorospirophosphorane. From this spirophosphorane the relative apicophilicity of the azide group was determined; it was found to be slightly more apicophilic than the phenoxy group. By a similar procedure a spirophosphorane containing a cyanide ligand was prepared.

This thesis is concerned with the determination of the gas-phase structures of large, asymmetric, sterically crowded molecules, with bulky alkyl ligands. Gas-phase electron diffraction is the best fluid phase technique available for the determination of structure. However, the many assumptions needed to refine these sterically encumbered molecules made complete structural determination impossible. In these cases, other fluid phase experimental data are called upon to fill in the structural detail, the main ones being liquid crystal nuclear magnetic resonance (LCNMR) and microwave spectroscopy. However, for the kind of systems under study in this thesis, it is not possible to collect data from these types of experiment. The combination of gas-phase electron diffraction data and <i>ab initio</i> calculations, called the SARACEN method, has overcome these problems. It has opened up the possibility of studying compounds previously beyond our capabilities. Advances in computational power mean that we can now calculate the structures of larger molecules with ~ 70 atoms to reasonable accuracy, and that our computers can now refine experimental structures up to 100 atoms in size. Previously, the SARACEN method has been applied to smaller systems of ~20 atoms. In this thesis, the method has been applied to much larger systems and many interesting features of the ligands, the effects they have on each other and the overall structures of molecules have been revealed. A series of disilanes with increasing steric bulk have been studied: 1,2-di-<i>tert</i>-butyltetrachlorodisilane, 1,1,2-tri-<i>tert</i>-butyldisilane, and 1,1,2,2-tetra-<i>tert-</i>butyldisilane. The structural results are surprising. The three-coordinate systems of tri(<i>tert</i>-butyl)sulfurtriimide and bis(trichlorosilyl)<i>tert-</i>butylphosphine have also been studied. Finally, the very unusual bis[bis(trimethylsily)methyl]phosphine and arsine radicals and the related dimers in the crystalline phase have been studied. Detailed analysis of the steric crowding of the solid structures has revealed the interesting new concept of ligands as energy reservoirs, which facilitate bond dissociation in the dimer.

No description available.

An <i>endo</i>-borneol based oxazolidinone 77 was used in a series of asymmetric transformations to assess its worth as a chiral auxiliary. In regard to titanium catalysed Diels-Alder reactions with cyclopentadiene, the acrylate and crotonate derivatives 87 and 101 exhibited poor selectivity; the acrylate displayed an optimum ratio of <i>endo</i> products of 2:1 and the crotonate of 3:1. Furthermore, the selectivity was shown to be dependent upon the order of addition of the reagents. The cinnamate derivative 102 reacted very sluggishly under the same conditions and only <i>ca.</i> 20% of the starting material was consumed after three days. When diethylaluminium chloride was employed as catalyst, the selectivity of 87 increased to 4:1 and that of the 101 increased to 6:1. Only 102 showed almost complete selectivity using this catalyse. The dienophile 87 reacted with isoprene to give a 2:1 mixture of products using titanium catalysts and 5:1 using diethylaluminium chloride catalyst. In regard to alkylation reactions, the lithium enolate 110 of the propionyl derivative of 77 condensed stereospecifically with benzyl bromide, but ethyl tosylate was inert to this nucleophile. Reaction of 110 with acetyl and propionyl chloride formed products with high selectivity, but small amounts of concomitant <i>O</i>-acylation occurred. Only reaction with methyl cyanoformate (Mander's reagent) occurred wholly at carbon, with a selectivity of 10:11. The reaction of this enolate with benzoyl chloride was stereospecific, but large amounts of enol product were also formed in this particular case. The enolate 10 underwent aldol condensation with isobutyraldehyde with 48% d.e. and 29% d.e. with acetaldehyde. However, the latter reaction was marred by the sluggishness of its reaction and the formation of dehydration products. The corresponding chlorotitanium enolate reacted with benzaldehyde to form a 6 : 5 ratio of <i>anti : syn</i> products. Use of excess Lewis acid furnished solely <i>anti</i> products. The analogous zinc enolate 132 was found to be completely unreactive towards even benzaldehyde complexed with diethylaluminium chloride and underwent chemical cleavage in boiling tetrahydrofuran.

No description available.

No description available.

The synthesis of a novel spiro-oxazolidin-2-one chiral auxiliary from both enantiomers of the common terpene camphene is described. The compound is formed <I>via</I> nitrene insertion and its structure has been determined by both NMR spectroscopy and X-ray diffraction studies. Evaluation of the functionalisation conditions for this hindered oxazolidin-2-one have been carried out and it has been observed that zinc salts give superior yields of <I>N</I>-acyl products compared to the use of the orthodox lithium or halomagnesium salts. It has been demonstrated that using suitable conditions the auxiliary is capable of inducing high degrees of stereoselectivity in a variety of enolate reactions including alkylation, acylation and aldol condensation. Unsaturated acyl derivatives undergo Diels-Alder cycloaddition with cyclopentadiene in the presence of diethylaluminium chloride to give adducts with very high diastereomeric excess. Michael additions of aluminium reagents to these acyl derivatives also give high diastereomeric excesses where the possibility of formation of a cationic intermediate exists. When such intermediates cannot be formed, in particular addition of trialkyl aluminium reagents, very low diastereomeric excesses are observed. 1,4-Conjugate addition of magnesium reagents is dependent on the presence of copper catalysts but the reactions proceed with high stereoselectivity and the intermediate enolates may be readily alkylated with equal specificity. In many cases the so formed adducts have been cleaved to give the newly created chiral fragments in high optical purity and chemical yield with almost complete recovery of the auxiliary (>90%). The application of a combination of stereoselective 1,4 conjugate addition and aldol condensation reactions has been applied to the synthesis of a number of substituted β-carboxy-γ-lactones (paraconic acids). The stereochemistry of these target molecules has been readily created with a high degree of specificity in very good chemical yield. In one attempted synthesis use of a surprisingly stereoselective lithium enolate aldol condensation is described. The origins of this selectivity has been proposed after considering the selectivities of a number of different substrates. However removal of the chiral product fragment from the auxiliary leaving both intact has been found to be highly dependent on both the functionality and stereochemistry of the adduct. Further applications of the auxiliary to short natural product synthesis and the potential of these routes is also briefly described.

This investigation examined the deracemisation of chiral amines via a cyclic oxidation and reduction sequence. The deracemisation relies on the combination of monoamine oxidase enzyme to perform an enantioselective oxidation of a single enantiomer of a racemic amine substrate to the imine. The imine is subsequently reduced back to the amine. Cycles of oxidation and reduction are required to produce high yields and enantiomeric excess. Directed evolution was used to screen for monoamine oxidase variants that showed superior activity towards novel secondary amine substrates. The specificity and enantioselectivity of the identified variants was examined. The optimised monoamine oxidases variant was used in the preparative deracemisation of secondary amine substrates in either whole cell or purified protein immobilised on resin. Various reducing agents were examined to identify those that showed the fastest rate of imine reduction under deracemisation conditions in order to minimise imine hydrolysis.

The need for asymmetric synthesis has been outlined and methods for generating asymmetry discussed. The chemistry of the well known 2,2'-disubstituted-1,1'-binapthyl system was reviewed and a novel chiral auxiliary has been designed around this system. Modifications were implemented to introduce originality into the system and hopefully increase stereoselectivity. These included an increase in steric bulk and the introduction of different co-ordinating functionalities. A quick and efficient synthesis of a series of novel biphenanthryl compounds has been developed in four steps from commercially available starting material. Resolution was effected at an early stage in the synthesis. The resolution was confirmed by X-ray crystallography and circular dichroism. The absolute configuration of the series has also been assigned. Investigations into the possible synthesis of a BINAP analogue, the chiral modification of lithium aluminium hydride, use as a chiral auxiliary and the possible synthesis of a chiral dihydropyridine reagent are also discussed.