Paderborn, Universiẗat, Diss., 2005.

No description available.

No description available.

Thesis advisor: Amir H. Hoveyda / Chapter 1. Efficient Z-Selective Synthesis of Allylic- and Alkenyl Boronates by Catalytic Cross-Metathesis Efficient Z-selective cross-metathesis reactions to furnish Z-(pinacolato)-allylboron and Z-(pinacolato)alkenylboron compounds through catalytic cross-metathesis are disclosed. Z-allylic boron compounds are generated by the use of catalytic amounts of a W-based monoaryloxide monopyrrolide (MAP) complex in up to 91% yield and 96:4 dr after allylation to benzaldehyde. Alkenylboron compounds are prepared in high yields and high Z selectivity in up to 93% yield and 97:3 Z:E. Cross-metathesis reactions with 1,3-dienes and aryl olefins are efficient and highly Z-selective. Combination of cross-metathesis and cross-coupling to synthesize anticancer agent combretastatin A-4 highlights the utility of this approach. Chapter 2. Synthesis of Macrocyclic and Acyclic Z-Enoates and (E,Z) or (Z,E) Dienoates by Catalytic Cross-Metathesis The first examples of kinetically controlled catalytic olefin metathesis reactions to generate Z-α,β-unsaturated macrocyclic and acyclic esters are disclosed. The synthesis of (E,Z) or (Z,E)-dienoates are also presented. Reactions promoted by 3.0–10 mol % of Mo-based monoaryloxide monopyrrolide complex proceed to completion to the desired macrocycles within 2–6 h at room temperature. Macrocycles of diverse ring sizes are formed in 79:21 to >98:2 Z:E selectivity. Pure Z isomers can be obtained after purification in up to 75% yield. Acyclic Z-α,β-unsaturated esters are prepared in the presence of acetonitrile to avoid using excess amounts of the more valuable cross-partner substrate. Spectroscopic investigations and X-ray analysis rationalize the positive effect of acetonitrile in the reaction system. Linear (Z)-enoates are generated in up to 71% yield and up to >98:2 Z:E. (E,Z)-Dienoates are generated with high Z selectivity as well. The utility of the ring-closing metathesis and cross-metathesis is highlighted by the synthesis of an (+)-aspicilin precursor and the C1–C12 fragment of biologically active natural product (–)-laulimalide. Chapter 3. Application of E-Selective Catalytic Ring-Closing Metathesis in the Total Synthesis of Dolabelides A, B, C and D Efforts towards the enantioselective synthesis of the dolabelide family of anti-cancer macrolides is presented. Development of a total synthesis incorporating a late-stage kinetically E-selective RCM is illustrated. Previous attempts to synthesize the macrolide by ring-closing metathesis (RCM) have demonstrated poor efficiency and low selectivity for the E isomer. Methodology developed in our group with acyclic trisubstituted cross-metathesis demonstrates that high selectivity can be achieved with stereodefined 1,2-disubstituted and trisubstituted olefins by the use of the proper catalyst and reaction design. Modern catalytic and stereoselective approaches towards the two main fragments of dolabelide are presented. More efficient and concise routes will be pursued to highlight the utility of the proposed disconnections and practicality of the total synthesis / Thesis (PhD) — Boston College, 2018. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

No description available.

The marine diterpene (–)-stolonidiol (1) has been shown to upregulate neuronal levels of acetylcholine. The mechanism through which a small molecule can impart this allosteric-like effect is currently unknown. A laboratory preparation of the natural product was undertaken in order to produce matieral for biological testing and elucidation of the unknown mechanism of action. During the course of this study, a tandem enyne-Suzuki reaction was investigated to form both rings of the fused bi-cyclic structure 26 in a single operation, but was met with undesired diastereoselectivity in the first cyclization step. The directing effect was found to be general on 1,6-homopropargyl enynes. Further efforts toward the molecule focused on an enantioselective formation of the cyclopentane core through an extension of a copper-mediated silylcyclization of epoxyalkyne 71. Using this intermediate two routes involving acrylate as a lynchpin to close the large ring were investigated. Additionally, a route designed to employ an intramolecular Knoevenagel condensation was explored to generate this ring system. / text

No description available.

This study has focussed on the application of synthetic, kinetic and exploratory theoretical methods in elucidating the reaction mechanisms of four Morita-Baylis-Hillman (MBH) type reactions, viz, i) the reactions of the disulfide 2,2'-dithiodibenzaldehyde with various activated alkenes in the presence of DBU and Ph₃P, ii) the reactions of chromone-3-carbaldehydes with MVK, iii) the reactions of chromone-2-carbaldehydes with acrylonitrile and iv) with methyl acrylate. Attention has also been given to the origin of the observed regioselectivity in Michaelis-Arbuzov reactions of 3-(halomethyl)coumarins. Cleavage of the sulfur-sulfur bond of aryl and heteroaryl disulfides by the nitrogen nucleophile DBU has been demonstrated, and a dramatic increase in the rate of tandem MBH and disulfide cleavage reactions of 2,2'-dithiodibenzaldehyde with the activated alkenes, MVK, EVK, acrylonitrile, methyl acrylate and tert-butyl acrylate has been achieved through the use of the dual organo-catalyst system, DBU-Ph₃P – an improvement accompanied by an increase in the yields of the isolated products. Detailed NMR-based kinetic studies have been conducted on the DBU-catalysed reactions of 2,2'-dithiodibenzaldehyde with MVK and methyl acrylate, and a theoretical kinetic model has been developed and complementary computational studies using Gaussian 03, at the DFT-B3LYP/6-31G(d) level of theory have provided valuable insights into the mechanism of these complex transformations. Reactions of chromone-3-carbaldehydes with MVK to afford chromone dimers and tricyclic products have been repeated, and a novel, intermediate MBH adduct has been isolated. The mechanisms of the competing pathways have been elucidated by DFT calculations and the development of a detailed theoretical kinetic model has ensued. Unusual transformations in MBH-type reactions of chromone-2-carbaldehydes with acrylonitrile and methyl acrylate have been explored and the structures of the unexpected products have been established using 1- and 2-D NMR, HRMS and X-ray crystallographic techniques. Attention has also been given to the synthesis of 3-(halomethyl)coumarins via the MBH reaction, and their subsequent Michaelis-Arbuzov reactions with triethyl phosphite. An exploratory study of the kinetics of the phosphonation reaction has been undertaken and the regio-selectivity of nucleophilic attack at the 4- and 1'-positions in the 3-chloro- and 3-(iodomethyl)coumarins has been investigated by calculating Mulliken charges, LUMO surfaces and Fukui condensed local softness functions.

Statistical copolymers of acrylonitrile (AN) and methyl acrylate (MA) were successfully prepared and characterized using reversible addition-fragmentation chain transfer (RAFT) copolymerization. A typical copolymer was charged with 15 wt. % MA content. This thesis describes a systematic variation of the RAFT copolymerization variables to optimize this system. In particular, the effects of chain transfer agent, initiator, temperature, and solvent on the copolymer properties were studied. / Master of Science

L'Imagerie par Résonance Magnétique (IRM) est à l'heure actuelle la technique de visualisation préférentiellement choisie par les chirurgiens. Cependant, cette technique ne permet pas de visualiser des prothèses à base de polymères, qu'elles soient dégradables ou non. Afin de mieux évaluer la fixation, l'intégration tissulaire et le devenir de l'implantation de ces prothèses polymères, il serait souhaitable qu'elles soient visibles par IRM. Ce travail présente donc la conception et la synthèse de copolymères biocompatibles visibles par IRM destinés à être introduit dans la composition de prothèses pour applications temporaires ou permanentes. En utilisant la modification chimique en position alpha de fonction ester décrite précédemment par notre laboratoire, nous avons greffé de façon covalente et par une liaison stable un chélate du gadolinium (le DTPA) sur la chaîne de la PCL (dégradable) et du PAM (non dégradable). Le gadolinium a ensuite été complexé par le DTPA greffé préalablement. Ces nouveaux copolymères ont été caractérisés par RMN et CES, et le taux de gadolinium évalué par ICP-MS. Des images d'IRM ont été réalisées in vitro et in vivo sur des appareils contenant des aimants de 7 Teslas (recherche) et 1,5 Teslas (clinique). Ces images montrent qu'un treillis en polypropylène enduit de copolymère greffé par un complexe DTPA-gadolinium est visible par IRM, ce qui laisse entrevoir un large champ d'applications pour ce type de composé. / Magnetic Resonance Imaging (MRI) is currently the visualization technique that surgeons preferentially choose. However this technique does not allow the visualization of polymer-based prosthesis, whether they are degradable or not. In order to best assess adhesion, tissue integration and the future of implantation of these polymer prosthesis, it would be advisable to make them visible in IRM. This work presents the conception and the synthesis of biocompatible copolymers visible in IRM meant to be implanted under the form of prosthesis for temporary or permanent applications. Using the chemical modification in alpha position of ester function, previously described by our laboratory, we grafted a gadolinium chelate, in a covalent way and forming a stable bond on PCL (degradable) and PMA (non degradable) backbone. Gadolinium was then complexed by DTPA previously grafted. Those new copolymers were characterized with NMR and SEC, and the rate of gadolinium was assessed by ICP-MS. MRI images were taken in vitro and in vivo on devices containing 7-Teslas (research) and 1,5 Teslas (clinical) magnets. These images show a poly(propylene) mesh coated with grafted copolymer containing complex gadolinium which is visible in MRI. It will consequently improve the prospects of applications for this kind of MRI-visible compound.