This thesis describes an extensive investigation of the O- to C-carboxyl transfer of oxazolyl carbonates using isothioureas as Lewis base catalysts. The structural requirements of simple bicyclic amidines and isothioureas to promote this transformation have been investigated, showing that the catalytic efficiency and product distribution of these reactions are markedly affected by the catalyst structure. The optimal isothiourea catalyst was efficiently applied to the rearrangement of a wide range of oxazolyl, benzofuranyl and indolyl carbonates. The structural motif of tetrahydropyrimidine-based isothioureas has then been evaluated in order to develop an asymmetric variant of the O- to C-carboxyl transfer of oxazolyl carbonates. A number of chiral isothioureas bearing stereodirecting groups in C(2) and/or C(3) have been synthesised and used in this rearrangement, showing that a C(2)-stereodirecting unit is essential for high enantioselectivity, with an additional C(3)-substituent increasing the reactivity. The optimal chiral C(2)-substituted isothioureas identified are general and efficient asymmetric catalysts for O- to C-carboxyl transfer of oxazolyl carbonates, generating a quaternary stereocentre with high enantioselectivity (up to 94% ee). The origin of the enantioselectivity of this process has been probed mechanistically and rationalised computationally. Having gained an insight into the structural motifs of isothioureas required to impart good catalytic activity and asymmetric induction in the O- to C-carboxyl transfer of oxazolyl carbonates, the mechanism of this reaction was probed using kinetic and mechanistic experiments. ¹⁹F NMR spectroscopic analysis allowed the evolution of product, by-product and intermediate throughout the reaction to be monitored while a number of crossover and stability experiments gave additional information about the catalytic cycle. Extension to a related system has been demonstrated with the O- to C-carboxyl transfer of furanyl carbonates, producing a mixture of α- and γ-butenolides depending on the nature of the Lewis base employed. DMAP gives a mixture of both regioisomers with a preference for the α-regioisomer, while NHCs lead predominantly to the γ-regioisomer. Chiral isothioureas have been used to promote this rearrangement, giving the major α-regioisomer with good enantioselectivity (up to 83% ee). To quantify the different reactivities observed with these isothioureas, their nucleophilicities and Lewis basicities using the stopped-flow technique have been determined. Finally, model studies toward the synthesis of the natural product calcaridine A, using the methodology developed herein, have been investigated.

Thesis (Ph.D.) -- McMaster University, 2001. / [Alpha] in title is a Greek letter. Includes bibliographical references. Also available via World Wide Web.

New Carbanion Rearrangement of Sulfur Compounds and Its Application Abstract This thesis reports the investigation of an unusual reversal in the metalation selectivity of alkyl aryl sulfones and sulfoxides and its application. Such compounds undergo initial directed ortho-metalation at −78 řC despite having an acidic α-hydrogen atom and the resulting aryllithiums rearrange subsequently completely to the initially expected α-sulfonyllithiums on warming. The scope and the limitations for this process were identified. Both carbanion types of sulfones were applied in reactions with various electrophiles. α-Lithiated sulfones generated upon the transmetalation process were used in Julia olefinations. A mechanistic study of the course of the transmetalation reaction is presented. The kinetics of the transmetalation were determined. Investigations concerning the concentration dependence, proton transfer equilibria between the different ortho-sulfonyllithium intermediates and crossover experiments provided the evidence that a concerted intermolecular pathway prevails. On this basis a new integrated synthetic approach to naturally occurring iridoids was developed. It is based on a tandem alkoxycarbonylation/oxidative radical cyclization of the olefins synthesized by the Julia reaction after the investigated...

I. Reductive dimerization of pentacyclo[5.4.0.0.^2,6.0^3,10.0^5'9]undecane-8-one-(PCU-8-one, 53) affords a mixture of meso and d,l pinacols (55a and 55b respectively). Acid promoted rearrangement of 55a and 55b conceivably can proceed with migration of C(7)-C(8) and/or C(8)-C(9) to form the corresponding pinacolone(s). In our hands, acid promoted rearrangement of 55a and 55b each proceeds with exclusive migration of C(7)- C(8) bond, thereby affording 58a and 59a respectively. Mechanistic features of this rearrangement are discussed. II. 4,7,1 l-trimethylpentacyclo[6.3.0.0.^2,6.0^3,l0.0^5,9]undecane-exo-4,exo-7-diol (23a) was successfully synthesized. This diol crystallizes in a helical tubuland lattice although its molecular structure does not possess C2 rotational symmetry.

The alumina-catalyzed Cope rearrangements of meso- and dl-3,4-diphenylhexa-1,5-diene were examined in detail, following up a preliminary observation by H. Berg at Portland State University. Commercial column-chromatography grade alumina was employed, and was further activated before use.by heating at 650-700° for four hours. Using a ratio of 20 mg of dl-3,4-diphenylhex-l,5-diene to 1 g of alumina in heptane, the Cope rearrangement was complete within 15 minutes at room temperature to give exclusively trans,trans-1,6-diphenylhexa-1,5-diene. This was identified.by melting point, infrared spectroscopy and vapor phase chromatography The catalyzed rearrangement of meso-3,4-diphenylhexa-l,5-diene was run using the same diene to alumina ratio. It was found that 31% of the meso-diene was converted to cis,trans- and trans,trans-l,6-diphenylhexa-1,5-diene at room temperature in four hours. Product iso-merization appeared to take place; the initial ratio of cis,trans-diene to trans,trans-diene was estimated to be 73:27. Another run was carried out at 60°, where the problem of isomerization of cis,trans-diene to trans,trans-diene was more pronounced. The rearrangement gave cis, trans-diene and trans,trans-diene in a ratio of 58:42, as estimated by extrapolation of the product ratio to zero time. Approximately 95% of meso-diene had reacted in one hour at this temperature. The extent of conversion of mes-diene was calculated by quantitative infrared spectroscopy, and the isomeric distribution of products was determined by vapor phase chromatography. The product distribution in the alumina-catalyzed rearrangements parallels that of the thermal Cope rearrangement, where dl-diene gives exclusively trans,trans-diene at 80° with a half-life of eight hours and meso-diene gives 63% cis,trans-diene and 27% trans,trans-diene at 120° with a half-life of 15 hours.

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<p> Phylogenetic analysis of gene order data is a developing area, and many questions on gene orders are still unresolved. In this project, we started from the OGRe database, where we obtained the mitochondrial genome information (after some corrections), designed a logarithm correction for breakpoint distance, applied distance matrix methods to both breakpoint distance and the logarithm of breakpoint distance for gene orders, and then focused on Arthropoda phylogeny We tried many phylogenetic methods to infer Arthropod phylogeny; however, no method yielded a satisfying result. We constructed an Arthropod phylogenetic tree based on both molecular and morphological evidences. After we estimated the phylogenetic tree, we used maximum likelihood methods to estimate branch lengths for tRNAs and proteins, calculated the breakpoint numbers and inversion numbers for gene orders, and calculated the correlations among these four measures. We found that: when gene order rearrangements and mutations on sequences are small, the changes are independent, and, when the rearrangements and mutations are large, the changes seem to be correlated. The branch lengths in the tRNA and protein trees are highly correlated in low mutation situations and less correlated when mutation rates are larger. </p> / Thesis / Master of Science (MSc)

Yes / Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14). / This work was supported by the Cancer Research UK-Cancer Imaging Centre (grant: C1060/ A16464), the Institute of Cancer Research and the University of Hull.