Thesis advisor: Shih-Yuan Liu / As BN-CC isosterism becomes an increasingly valuable strategy to expand chemical space and increase molecular diversity, methods for functionalizing and utilizing BN-heteroarenes remain limited in comparison to those for all-carbon arenes. Described herein are initial studies aimed at developing methods for the late-stage functionalization of substituted 1,2-azaborines through controlled aryl and alkyl migrations. Furthermore, investigations into the application of B-aryl and B-alkyl 1,2-azaborines as transmetalation reagents in Suzuki-Miyaura cross-coupling reactions are presented. / Thesis (MS) — Boston College, 2019. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Azaarenes are of widespread chemical significance, being present in numerous chiral, biologically active natural products, and serving as building blocks for the discovery of new medicines, agrochemicals, and functional molecules. Consequently, the development of new methods to prepare chiral azaarene-containing compounds is an important goal. The Lam group and others have previously demonstrated the synthetic utility of azaarenes as activating groups in a variety of catalytic asymmetric processes, which are summarised in Chapter 1. Chapter 2 presents a recent achievement in this area: the development of a mild and highly enantioselective conjugate addition of acetylazaarenes to nitroalkenes, under nickel catalysis, to afford densely functionalised products. The reaction scope includes a broad range of acetylazaarenes as well as (hetero)aromatic and aliphatic nitroalkenes. When α-nitroacrylate esters are employed as conjugate acceptors, products bearing a quaternary stereogenic centre are formed in high yield and with excellent enantioselectivity. The methodology is easily scalable, allowing multigram preparations to be carried out with catalyst loadings of 1 mol% without loss of yield or enantioselectivity. Further transformations of the products, including diastereoselective transfer hydrogenation, are briefly described. Finally, Chapter 3 gives an overview of unsuccessful efforts to develop routes to α-sulfonyl organoboron compounds, for subsequent use in ate complex homologation chemistry, via catalytic asymmetric conjugate addition processes.

This thesis explores the synthesis and conformational behaviour of hexahydropyrimidines and related heterocycles, with particular emphasis on 5- hyrdohexahydropyrimidines. The conformational behaviour of these compounds was investigated using dynamic NMR spectroscopy, molecular modelling techniques and X-ray crystal structure analysis. The conformational behaviour of 5- hyrdohexahydropyrimidine, hexahydropyrimidine and their analogous oxygen compounds as well as a series of hexahydropyrimidines with various exocyclic substituents, were examined. The preferred conformations of all these compounds are attenuated by a combination of steric and electronic influences. These influences include intramolecular hydrogen bonding as well as anomeric and gauche interactions. The conformational behaviour of the selected seven membered benzodiazepine rings, which share structural characteristics with the six-membered 5- hyrdohexahydropyrimidines was also explored. The increased flexibility of the seven membered rings facilitates intramolecular hydrogen bonding, which in turn retards ring inversion in these systems / Doctor of Philosophy (PhD)

No description available.

Neutral radicals have been pursued as building blocks for conductive and magnetic materials for several decades. Carbon-based materials are typically plagued by dimerization and quenching of spins, but the incorporation of heteroatoms has led to many systems that remain open-shell. Radicals based on the thiazyl subunit, which are the subject of this thesis, have evolved through many generations. While the early frameworks possessed a very high onsite Coulomb repulsion energy, U, which caused the spins to be localized so that the radicals were trapped in Mott insulating ground states, the development of resonance stabilized bisdithiazolyl radicals, and their selenazyl counterparts, has led to decreased values of U, in addition to inducing major improvements in the bandwidth, W. Variation in the ligand environment and selenium content can significantly change solid state packing and hence physical properties. This so-called effect of chemical pressure has been explored and structure-property correlations have been well established. In addition to studies involving the variation of chemical pressure, in this thesis the effect of physical pressure on these resonance stabilized heavy atom radicals is presented. In the radical building blocks of the present systems there are four possible combinations of sulfur and selenium atoms, sets of which constitute a family. The families may crystallize as an isostructural set in the solid state, but this is rare. Earlier work established that radicals in one isostructural family crystallize as undimerized π-radicals in the P4¯21m space group, the selenium variants of which all order magnetically. In this thesis, subtle molecular modification of this family is first explored. Exploration of the substituent effects with selenium fixed in the central position of the heterocycle has provided radicals that order as bulk ferromagnets in the range Tc = 9–12 K. The highest Tc ferromagnets in this group are those based on the all-selenium framework. The magnetic response of these radicals was studied under pressure, and it was discovered that with the initial application of pressure, Tc rises from 17–18 K to 21–24 K, before retreating upon further pressurization. In the 7–9 GPa range, the magnetic insulators begin to metallize, as evidenced by the loss in activation barrier to conductivity and a saturation of the resistance to a finite value at low temperature. The crystal structures in the entire pressure range have been determined and the changes in transport properties have been attributed to decreased slippage of the π-stacks with increasing pressure. Although most of the resonance stabilized bisdithiazolyl radicals and their selenium variants are undimerized in the solid state, a few derivatives exist that dimerize through unique 4-center 6-electron S•••E–E•••S σ-bonds. When E = Se, hypervalent σ-dimerization is especially prevalent. Under ambient conditions, these materials pack in crossbraced π-stacks and exhibit semiconducting behavior. Upon mild pressurization (P ≤ 5 GPa), however, conductivity increases 5–6 orders of magnitude and the activation energy decreases remarkably. Solid state structures have now been elucidated for these dimers under pressure. For two of the variants, including one (rare) E = S σ-dimer, increasing pressure results in simple contraction of the structure. This leads to enhanced orbital overlap and gradual coalescence of the valence and conduction bands, eventually leading to metallization at P > 13 GPa. This behavior is in sharp contrast to a previously reported σ-dimer, which undergoes a transition to a π-dimer at 5 GPa, the structure of which leads to abrupt closure of the HOMO-LUMO gap and, hence, the sudden onset of a weakly metallic state. As a departure from the behavior of any of the other known hypervalent σ-dimers, one bisdithiazolyl variant undergoes an abrupt S = 0 → S = ½ transition. This change can be initiated thermally, optically and with mild pressure. The thermal process, which is observed in the magnetic susceptibility measurements, is hysteretic, with T↑ = 380 K and T↓ = 375 K, giving rise to a small region of bistability. Irradiation results in the photomagnetization of the metastable S = ½ state that persists to an unprecedented relaxation temperature of 242 K. Under the influence of pressure, the same dimer-to-radical transition occurs (at room temperature) near 0.7 GPa. In all cases, the crystal structure of the metastable excited state has been determined by single crystal or powder X-ray diffraction. The novel behavior of the σ-dimer is in addition to the existence of a second polymorph of this material, which is paramagnetic and belongs to the P4¯21m space group under ambient conditions. Further exploration of the effects of chemical pressure on bisdithiazolyl radicals has led to new systems with extremely long alkyl chains. This was explored for the purpose of separating the plates to generate lower dimensional frameworks. The crystal structure of one derivative belongs to the familiar tetragonal space group P4¯21m. However, upon increasing chain length of the alkyl substituent, an isomorphous set is generated, with all three compounds crystallizing in the P21/c space group. The structures consist of pairs of radical π-stacks pinned together by strong intermolecular F•••S' bridges to create spin ladder arrays. The slipped π-stack alignment of radicals produces close non-covalent S•••S' interactions which serve as the “rungs” of a spin ladder, and the long chain alkyl substituents serve as buffers that separate the ladders from each other laterally. The “legs” of the spin ladder are generated by magnetic exchange along the π-stacks. Magnetic susceptibility measurements reveal the presence of very strong antiferromagnetic coupling in all three compounds, which have been successfully modeled as strong-leg spin ladders.

Nitrogen-containing heterocycles are of vital importance for the pharmaceutical and agrochemical industries. The Beauchemin group has been studying rare, amphoteric nitrogen-substituted isocyanates over the past years, and showed that their [3+2] alkene cycloaddition and cascade reactions provide access to a variety of NNCO containing heterocyclic compounds. This triggered interest into the reactivity of the parent N-isothiocyanates, which are also rare, and led to the discovery of aminothiocarbonylation reactions. The products formed are azomethine imines which contain a cyclic -aminothiocarbonyl motif, thus providing a cycloaddition route to these useful dipoles from simple starting materials. Such aminothiocarbonylation reactions were developed with both alkenes and imines as substrates.Apart from cyclic azomethine imine formations, efforts have also been made toward forming the acyclic azomethine imines as intermediates. These intermediates undergo [3+2] cycloaddition to form thiocarbamoyl pyrazolidine derivatives, and a preliminary substrate scope for this new intermolecular reactivity is presented. Other preliminary results include an unexpected Chugaev type reactivity. Collectively, these results show that N-isothiocyanates hold significant potential for the development of new reactivity.

No description available.

This thesis is concerned with the development of cyclisation strategies that allow entry to polycyclic heterocycles and medium sized ring systems. Radical additions to pyridines are developed and methodologies explore the differences between the homolysis of C-Br and C-I bonds. Mechanisms are described for the unexpected ipso additions to the pyridines. Work towards the synthesis of the stegnans and dimethylgomisin illustrates the attempts to utilise the ipso addition to form medium sized ring systems. A new method of synthesising these medium sized ring systems is discussed. Progress towards a general methodology is described and shows the opportunities for which it could be utilised. A literature review of the synthesis of heterocycles via radical cyclisations is presented.

Grâce à ses propriétés uniques, le groupement pentafluorosulfanyle (SF5) a récemment retenu beaucoup d'attention. Ce substituant encombrant, hautement lipophile et électro-attracteur est souvent considéré comme un "super groupement trifluorométhyl". Aujourd’hui, la chimie de groupement SF5 est un domaine de la chimie du fluor qui se développe rapidement, et les méthodologies de synthèse des nouveaux « building-blocks » pentafluorosulfanylés sont constamment développées. Néanmoins, les méthodes permettant l'introduction du groupement SF5 dans les hétérocycles restent encore assez limitées. L’objectif de cette thèse était de synthétiser des nouveaux « building-blocks » pentafluorosulfanylés, d’une part, et de développer des nouvelles approches synthétiques, conduisant à des hétérocycles azotés originaux, substitués par un groupement SF5, d’autre part. Dans la première partie de notre travail, nous avons développé une synthèse en 4 étapes, conduisant à de nouveaux esters et amides acryliques substitués par un groupement SF5, à partir des dérivés commerciaux de l’acetate allylique. En utilisant la même stratégie, quelques nouveaux allylsilanes pentafluorosulfanylés ont été synthétisés. Nous avons aussi développé une réaction d’allylation des aldéhydes, catalysée par indium, en utilisant le bromure SF5-allylique, conduisant aux alcools alpha- et gamma-homoallyliques correspondants.Dans la deuxième partie, deux stratégies différentes pour la synthèse de nouveaux hétérocycles SF5-substitués, ont été explorées. La première était la fluoration directe des thiols ou disulfures hétérocycliques, suivant la procédure de Umemoto. La deuxième approche était basée sur les réactions de cycloaddition de nos "building-blocks" pentafluorosulfanylés. Ainsi, nous avons développé avec succès la synthèse des premières pyrrolidines et isoxazolidines pentafluorosulfanylées. Enfin, des post-fonctionnalisations des SF5-pyrrolidines ont été effectuées, conduisant aux plusieurs "plateformes" pentafluorosulfanylées qui pourraient être facilement incorporées dans les molécules d’intérêt biologique. / Due to its unique properties, the pentafluorosulfanyl (SF5) group has recently reached much attention. This bulky, highly lipophilic and electron-withdrawing substituent is often called as a “super-trifluoromethyl group”. Currently, the SF5-chemistry is becoming a fast growing field of the fluorine chemistry and the new pentafluorosulfanylated building-blocks are under continuous development. Nevertheless, the methods for the introduction of the SF5-group into heterocycles remain still quite limited.The aim of this thesis was to synthesize new pentafluorosulfanylated building-blocks, on the one hand, and to develop new synthetic approaches leading to original pentafluorosulfanylated nitrogen-containing heterocyles, on the other hand.In the first part of our work, we have developed an efficient four-step synthesis of new SF5-acrylic esters and amides, starting from commercially available allyl acetate derivatives. Using the same strategy, several new pentafluorosulfanylated allylsilanes were synthesized. We have also developed an In-mediated allylation reaction of aldehydes, using the SF5-allyl bromide, leading to the corresponding pentafluorosulfanylated alpha- and gamma-homoallylic alcohols.In the second part, two different strategies for the synthesis of new SF5-substituted heterocycles were explored. The first one was the direct fluorination of heterocyclic thiols or disulfides, according to the Umemoto’s procedure. The second approach was based on the cycloaddition reactions of our pentafluorosulfanylated building-blocks. As a result, we have successfully developed the synthesis of the first SF5-substituted pyrrolidines and isoxazolidines. Finally, post-functionalizations of SF5-pyrrolidines were performed, leading to several pentafluorosulfanylated scaffolds which could be easily introduce into molecules of biological interest.

No description available.