The aim of the work carried out in this thesis is to develop new efficient catalytic systems for the synthesis of enantioenriched secondary alcohols. The access to this class of important synthetic intermediates is possible either by nucleophilic addition of organometallic reagents to aldehydes or by reduction of prochiral ketones catalysed with chiral complexes. We have thus developed two new catalytic systems for the asymmetric hydrosilylation of ketones using polymethylhydrosiloxane (PMHS) as an inexpensive reducing agent. A first approach is based on the synthesis of new N, S ligands and zinc complexes bearing a ferrocenyl backbone with planar chirality. Those compounds were prepared and evaluated first in the addition of diethyl zinc to aldehydes, reaching enantiomeric excesses up to 74%. The precatalysts were also evaluated in the reduction of prochiral ketones with PMHS. In that case, a good reactivity was observed and enantioselectivities up to 61% could be reached. It is assumed that a zinc hydride complex formed by thermal ß-elimination of the corresponding ethyl complex is the active species. This catalytic system also allows the hydrosilylation of dialkyl ketones, a challenging goal in asymmetric catalysis. In a second part of this work, we have developed a new catalytic system for hydrosilylation of ketones based on the hypothetical formation of a chiral cobalt hydride catalyst. This intermediate is supposed to be formed by reaction of the corresponding neutral cobalt (II) complex with tetrabutyl ammonium triphenyldifluorosilicate (TBAT) as activator and a silane. Following a preliminary screening, salen type ligands were found to be the most efficient when activated with TBAT in presence of PMHS. Modifications on this structure by replacing the phenol group of the ligand by various sulfonamide groups led, after optimisation of the reaction parameters, to a highly efficient catalytic system with enantioselectivities reaching 84 % for the reduction of tetralone. This work should thus open new perspective for the design of highly enantioselective and low cost catalytic systems for the hydrosilylation of prochiral ketones.

Nature has gifted peptides as important modulators in the human body, but these types of molecules often have not been favored when we were looking for therapeutic agents. The poor bioavailability, fast degradation and until recent high manufacturing costs of some bioactive peptides lowered their potential usage in the health industry. Under these circumstances, unnatural amino acids were developed as indispensible tools providing enormous support to peptide science. By incorporating proper unnatural amino acids into a peptide or protein, we now can significantly improve peptide's or protein's half-life, cell permeability, bio-distribution, etc. In addition, their potency and receptor/acceptor selectivity could also be enhanced. Site-specific modifications of peptides and proteins under physiological conditions with the use of unnatural amino acids also have been made easier with the advance of biotechnology. Therefore, my research described in this dissertation contributes to the efforts in the development of novel unnatural amino acids. In particular, I have focused on novel methods in the synthesis of anti beta-functionalized gamma,delta-unsaturated amino acids. These amino acids have special interests in peptide chemistry: they can provide conformational constraints to the peptide 3D structures; the beta-functionalization allows the introduction of pharmaceutically interesting side chain groups; and the terminal double bond which is orthogonal to peptide synthesis provides access to further chemical modifications. Two general methodologies for the synthesis of both racemic and optically active anti beta-functionalized gamma,delta--unsaturated amino acids were developed by using the thio-Claisen rearrangement (TCR) reaction. Excellent diastereoselectivies and enantioselectivities were obtained when C2-symmetric chiral auxiliaries were selected to control the stereochemistry outcome. The mechanism and the scope of the TCR reaction were also studied, showing unique advantages in the preparation of these biological interesting amino acids.Another effort of developing angiotensin II type 1 (AT1) receptor biased peptide ligands is also documented in this dissertation. The AT1 receptor is a 7-transmembrane G-protein coupled receptor, which recent researches have shown could be activated through a beta-arrestins only, but G-protein independent, pathway. We synthesized 12 analogs of Sar1,Ile4,Ile8-AngII (SII), and tested them in biological assays, and obtained valuable information for further "perfect" biased ligands design.

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Several tetrahydroisoquinoline (TIQ) diamine derivatives were prepared for use as ligands in asymmetric transfer hydrogenation (ATH) of acetophenone of which 17 intermediates and the eight target ligands were novel compounds. The initial design followed that of Noyori, who presented the efficiency of his monotosylated diamine in ATH. A series of eight novel secondary amine derivatives (78a-g and 88) were prepared with substituents that influenced the electronics and the sterics of and around the nitrogen donor. Ligand 71 was shown to have no activity for the ATH of acetophenone. It was apparent from experimental observations that a balance between the electronic and steric characteristics of the substituent was necessary to facilitate activity. It was found that ligand 78d possessing a benzyl group, had the greatest activity (81 % conv.). The greatest selectivity was obtained with ligand 78f (77 % ee) having a chiral phenylmethyl substituent. It was discovered in the case of the active diamine ligands that an optimised 1500 equivalents of water was required in order to demonstrate any enantioselectivity. The exact role of the water has never been ascertained, although there are many publications in which the effect of water has been examined. The most active metal precursor was also investigated and [RhCl2(Cp*)]2 was found to be the best for these TIQ diamine ligands in the specified model reactions. This work has recently been accepted for publication and has established criteria for further rational design on this system. / Thesis (M.Sc.)-University of KwaZulu-Natal, Westville, 2010.

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Over the last few decades the interests of statistical physicists have broadened to include the detailed quantitative study of many systems - chemical, biological and even social - that were not traditionally part of the discipline. These systems can feature rich and complex spatiotemporal behaviour, often due to continued interaction with the environment and characterised by the dissipation of flows of energy and/or mass. This has led to vigorous research aimed at extending the established theoretical framework and adapting analytical methods that originate in the study of systems at thermodynamic equilibrium to deal with out-of-equilibrium situations, which are much more prevalent in nature. This thesis focuses on a microscopic model known as the asymmetric exclusion process, or ASEP, which describes the stochastic motion of particles on a one-dimensional lattice. Though in the first instance a model of a lattice gas, it is sufficiently general to have served as the basis to model a wide variety of phenomena. That, as well as substantial progress made in analysing its stationary behaviour, including the locations and nature of phase transitions, have led to it becoming a paradigmatic model of an exactly solvable nonequilibrium system. Recently an exact solution for the dynamics found a somewhat enigmatic transition, which has not been well understood. This thesis is an attempt to verify and better understand the nature of that dynamical transition, including its relation, if any, to the static phase transitions. I begin in Chapter 2 by reviewing known results for the ASEP, in particular the totally asymmetric variant (TASEP), driven at the boundaries. I present the exact dynamical transition as it was first derived, and a reduced description of the dynamics known as domain wall theory (DWT), which locates the transition at a different place. In Chapter 3, I investigate solutions of a nonlinear PDE that constitutes a mean-field, continuum approximation of the ASEP, namely the Burgers equation, and find that a similar dynamical transition occurs there at the same place as predicted by DWT but in disagreement with the exact result. Next, in Chapter 4 I report on efforts to observe and measure the dynamical transition through Monte Carlo simulation. No directly obvious physical manifestation of the transition was observed. The relaxation of three different observables was measured and found to agree well with each other but only slightly better with the exact transition than with DWT. In Chapter 5 I apply a numerical renormalisation scheme known as the Density Matrix Renormalisation Group (DMRG) method and find that it confirms the exact dynamical transition, ruling out the behaviour predicted by DWT. Finally in Chapter 6 I demonstrate that a perturbative calculation, involving the crossing of eigenvalues, allows us to rederive the location of the dynamical transition found exactly, thereby offering some insight into the nature of the transition.

In the past decades, China's military modernization and economy fast development has increasingly attracted international attention, especially the United States. In addition, the PLA has begun to study the revolution in the military affairs (RMA) by focusing on asymmetric warfare capabilities under high-tech conditions. China definitely believes that asymmetric warfare operations have the advantage of creating a more smart attack style to avoid directly facing U.S. powerful military strength. In summary, asymmetric warfare operations are considered by the PLA as a kind of warfare that combined both the thinking of China's classic military strategist Sun Tzu "using the inferior to defeat the superior" and the demand of the modern information technology such as IW applications. In face of China's development of asymmetric warfare capabilities, the United States must deeply think about how to deal with the threat from China's asymmetric warfare operations, which is gradually becoming the superpower in the world.

Thesis advisor: James P. Morken / This dissertation will discuss in depth four main projects pertaining to the synthesis and utility of organoboronates for the construction of enantioenriched small molecules. First, reaction optimization and substrate scope expansion of the platinum-catalyzed enantioselective diboration of alkenes are reported. Based on extensive experimental and computational mechanistic analysis, a preliminary stereochemical model is also proposed. A practical boron-Wittig reaction is presented in which synthetically challenging di- and trisubstituted vinyl boronates can be accessed in a highly stereoselective fashion from readily available starting materials. The enantioselective diboration of cis- and trans-vinyl boronates furnished novel 1,1,2-tris(boronate) esters in up to 95:5 er. The intermediate tris(boronate) esters were employed successfully in deborylative alkylations to furnish enantioenriched internal vicinal bis(boronates) in excellent diasteoselectivity. In the final chapter, an enantioselective palladium-catalyzed intramolecular Suzuki-Miyaura coupling between allyl boronates and aryl electrophiles is disclosed. The newly developed transformation provides enantioenriched 5, 6, and 7-membered carbocycles in up to 93:7 er. / Thesis (PhD) — Boston College, 2015. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Chapter 1. Review of concept and methodology development for asymmetric allylation of carbonyls and imines. Chapter 2. Description of the catalytic asymmetric addition of allyltrichlorosilane to aldehydes catalyzed by a proline-based N-oxide catalyst. Chapter 3. Introduction of the first catalytic asymmetric silylation of alcohols for desymmetrization of meso-diols. Chapter 4. Presentation of asymmetric silylation for synthesis of chiral syn-1,2-diols by kinetic resolution or divergent reaction on a racemic mixture. / Thesis (PhD) — Boston College, 2008. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.