Ruthenium-alkylidene catalysts are widely used in organic synthesis to generate new C=C bonds in a process known as olefin metathesis. Much research has been dedicated to examining the organometallic species responsible for this transformation, and understanding the benefits and limitations of current state-of-the-art catalysts allows for the design of new and more efficient alternatives. Over the past decade, a topic of much debate has been the so-called “boomerang” (or release-return) mechanism, and whether it operates in the Hoveyda catalysts. The ability of the styrenyl ether ligand, once released from the catalyst during initiation, to be recaptured by the vulnerable active species, has major implications in catalyst recyclability. Chapter 3 describes the use of a 13C-labeled styrenyl ether ligand, in conjunction with an unlabeled second-generation Hoveyda catalyst, to confirm the operation of this mechanism during catalysis. This study demonstrated that the labeled styrenyl ether ligand competes with the substrate for the four-coordinate active species: the labeled moiety rapidly incorporates into the Hoveyda catalyst during both ring-closing- and cross-metathesis examples. Chapter 4 focuses on addressing the selectivity challenges associated with olefin metathesis, particularly during RCM macrocyclization reactions where E/Z mixtures are typically obtained. Designing catalysts that can dictate and control the stereochemistry of a product mixture minimizes waste, and ultimately reduces cost by eliminating the need for separation techniques. A great deal of research has focused on constructing catalysts with ligands that can exert the appropriate steric pressure on a metallocyclobutane intermediate, in order to generate the desired Z-product. Chapter 4 of this thesis examined the ability of a Hoveyda- and Grubbs-type catalyst containing monothiolate ligands, to promote Z-selective RCM macrocyclization. Catalyst lifetimes were also examined, in addition to the impact of altering reaction conditions, specifically concentration, on product distribution. These experiments afford information that will aid in the design of improved catalysts for Z-selective RCM macrocyclization.

The addition of allyl magnesium and allyl indium reagents to a key TBS protected norbornenyl building block, synthesised in 6-steps from commercially available 1,1-dimethoxy-2,3,4,5-tetrachlorocyclo-pentadiene, has been achieved providing the syn addition products with high diastereoselectivity. The subsequent exposure of the addition products to metathesis conditions, in the presence of ethylene, then provided cis fused [3.0.3]-carbocycles with very high regioselectivity, via a Ring Rearrangement Metathesis (RRM) transformation. The high level of regioselectivity is due to the rearrangement of the metathesis intermediates to give the more thermodynamically stable product This work has been expanded to include [2.2.2]-bicycles, addition of allyl magnesium and indium reagents to a key bicyclo[2.2.2]oct-5-en-2-one has been achieved, giving both diastereoisomers, separable by chromatography. The subsequent exposure of the addition products to optimised metathesis conditions, then provided cis fused [3.3.1] carbocycles with very high regioselectivity, via a RRM transformation. It was found that two possible cyclisation pathways occur under our reaction conditions; pathway (a) will yield a cis-fused [4.0.3]-carbocycle while pathway (b) will deliver the observed [3.3.1]-carbocycle.

Thesis advisor: Amir H. Hoveyda / Chapter One: Stereoretentive Cross-Metathesis of Trisubstituted Olefins The development of stereoretentive olefin metathesis catalysts has solved a long-standing problem in the field, allowing for trisubstituted alkenes to be synthesized in high stereochemical purity and under kinetic control. E- as well as Z-isomers of trisubstituted alkenyl halides, nitriles, and allylic alcohols can be accessed through cross-metathesis of commercially available and easily accessible alkenes. Through the use of the same strategy, macrocyclic trisubstituted alkenes have been accessed in either isomeric form through stereoretentive ring-closing metathesis of the corresponding diene starting materials. Thus, for the first time, a wide range of E- and Z-trisubstituted alkenes can be obtained selectively through olefin metathesis, regardless of the underlying thermodynamic preferences. Chapter Two: Development of Catalytic Stereoretentive Cross-Metathesis of Trisubstituted Alkenyl Bromides We have introduced a general and widely applicable strategy for the synthesis of E- and Z-trisubstituted alkenyl bromides through cross-metathesis. The reaction is applicable to terminal, disubstituted, and trisubstituted olefins bearing a variety of functional groups including alkenes with α-, or β-branches. The requisite stereodefined cross-partners, E- and Z-2-bromo-2-butene are commercially available and can be synthesized with ease in one step from abundant starting materials. This represents a notable improvement over our previous approach, where the non-halogenated alkene starting material had to be prepared through cross-coupling in high stereochemical purity to ensure high stereoretention in the subsequent cross-metathesis. Catalysts derived from Mo monoaryloxide pyrrolide complexes, some of which are commercially available, are optimal for this transformation. The applicability of the approach is underscored through the formal synthesis of phomactin A with improved overall yield and step count. Chapter Three: Total Synthesis of Ambrein We have completed a total synthesis of ambrein, a terpenoid isolated from whale secretion, a much sought perfume ingredient. The approach involved joining two fragments through formation of the central trisubstituted alkene. Our route entailed a sequence of cross-metathesis of alkenyl bromides and cross-coupling, providing access to a previously difficult-to-access trisubstituted olefin with high efficiency and selectivity. One fragment was generated from a readily accessible enantiomerically enriched compound, sclareolide, and the other from inexpensive methylcyclohexenone. The stereogenic center of the latter was established through a NHC-Cu-catalyzed enantioselective allylic substitution, which was followed by differentiation of these alkenes through site-selective epoxidation. The total synthesis is more efficient and offers a more practical route to ambrein. Chapter Four: Stereoretentive Cross-Metathesis of Trisubstituted α,β-Unsaturated Carbonyl Compounds We have developed a strategy for the synthesis of Z- and E-Trisubstituted α,β-unsaturated carbonyl compounds through stereoretentive CM involving commercially available or easily accessible alkene substrates. The method is applicable to a variety of α,β-unsaturated esters, thioesters, and acyl fluorides. Furthermore, mono-, di-, and trisubstituted alkenes can be used as starting materials. Transformations may be carried out on gram scale and, in some cases, with commercially available Mo catalysts. The utility of the catalytic approach was highlighted through synthesis of previously accessed intermediates more directly and with improved efficiency. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

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This thesis describes studies directed to the ring opening metathesis polymerisation (ROMP) of some fluorinated compounds using a range of well-defined initiators. Chapter 1 reviews some general aspects of olefin metathesis and ring opening metathesis polymerisation of relevance to the work described in this thesis. Topics such as piezo- and pyro-electricity and optical and electrical properties of conjugated polymers are introduced and these receive more detailed attention later in the thesis. Chapter 2 describes the synthesis, characterisation and properties of . poly(bis(trifluororaethyl)norbomadiene) in detail. The use of various initiating systems that have been used previously and the effect they have on the tacticity of the resulting polymer raicrostructure are discussed. The latter part of this chapter reviews some of the current thinking concerning the detailed mechanistic aspects of this polymerisation. Chapter 3 reviews attempts directed to an improvement in tacticity control in the synthesis of poly(bis(trifluoromethyl)norbomadiene). The synthesis and activity of the new well-defined initiators used in these studies are reported. It is shown that varying the nature of the ancillary Ligands surrounding the metal centre can have a dramatic influence on the tacticity of the resulting polymer. Chapter 4 reports studies directed to an examination of the limits of the well controlled synthesis of poly(bis(trifluoromethyl)norbornadiene). The syntheses of high trans and high cis, highly tactic poly(bis(trifluoromethyl)norbornadiene samples using well-defined initiating systems are described. It is shown that by varying the monomerinitiator ratio, samples with a wide range of molecular weights can be achieved and these are reported. Chapter 5 describes experiments concerning the ROMP of fluorinated monomers containing six membered rings. In particular ROMP studies of the monomers, 2,3-bis(trifluoromethyl)bicyclo[2.2.2]octa-2,5-diene . and 2,3- (tetrafluorobenzo)bicyclo[2.2.2]octatriene are described finally, Chapter 6 provides a summary of the work reported and outlines some ideas for future studies.

1. In the first part of this thesis, the concept of a tether based intramolecular crossed -acyloin reaction mediated by heterogeneous lithium/ 4,4' -di-teti-butylbiphenyl (Li/DBB) reducing conditions was examined. The objective of the project was to accomplish an intramolecular crossed-acyloin reaction, by employing non-symmetric di-esters, linked with a suitable tether (diol) between the two acyl functionalities. Chapter 1: Introduction - Acyloin Condensation. The concept of carbon-carbon coupling reactions between two carbonyl functionalities to synthesise a-hydroxyketone (acyloin) moieties is described. Generally, there are two methods, either by bimolecular reductive coupli ng of esters, known as acyloin condensation or the umpo/ung dimerisation of aldehydes, known as benzoin condensation. The background and recent developments in these reaction categori es are discussed in this section. In addition, this section outlines the project's aims and describes the previous work conducted in the group. Chapter 2: Results & Discussion - An Alternative Route to Crossed-ocyloin In this section, the tether based intramolecular crossed-acyloin reaction mediated by Li/DBB reducing conditions is introduced. This work is based on the hypothesis that a suitable tether, could promote an intramolecular crossed-acyloin reaction. The objective was successfully achieved through a series of competition experiments, which demonstrated that the application of exo-exo norbornenediol as a tether exclusively formed crossed-acyloin products. This discovery was accompanied by an investigation into regi oselective crossed-acyloin reaction. 2. In the second part of this thesis, the Sharpless Asymmetric Epoxidation (SAE) desymmetrisation reaction of O'-symmetric diene 1,3-diols was exami ned. It was suggested that formation of the epoxide would trigger a stereoselective 5-exo-tet ring closure to deliver predominately trans-THF adducts. Chapter 3: Introduction - Metal Mediated Synthetic Routes to trans-2,5-Disubstituted THFs This section introduces the transition metal mediated cyciisation of bishomoallylic alcohol, to the corresponding trans- THF moieties. In particular, the development and application of three methods were highlighted; rhenium mediated (3+2) oxidative cyclisation, cobalt catalysed oxidative cyclisation and an rc-allylpalladium complex catalysed reaction. In addition, the concept of the Sharpless Asymmetric Epoxidation (SAE) is introduced and the project objectives are outlined. Chapter 4: Results & Discussion - A NOJel Route Towards trans- THFs The primary effort was to design a robust route to form the test substrate, (3R,55}hepta-1,6-diene- 3,5-diol, which was accomplished in good yield by Ring Opening/Crossed metathesis (ROM) of silyl ether protected (1 R, 35 }cyclopent-4-ene-1,3-diol. The expe rimental results have demonstrated that SAE of the diene 1,3 diol formed trans-THF. Chapter 5: Experimental Full experimental procedures and characterisation of the synthesised molecules are reported.

The work described in the thesis is concerned with making new polymeric materials via ring opening metathesis polymerisation (ROMP) using a well-defined ruthenium carbene as an initiator. The object of the study was to provide a process for producing shaped articles by introducing a reactive liquid mixture into a mould in which the reacting liquid mixture undergoes ROMP in the bulk to produce the moulded article. Mono- and difunctional imidonorbomene derivatives were used as monomer and crosslinker respectively. The properties of the cured samples were determined by sol-gel analysis, DSC, TGA, nmr and IR spectrometry. Gel fraction, Tg and content of unreacted monomer were used to characterise the cured samples. The results indicated a strong dependence of the polymers appearance and properties on the polymerization formulation and protocol, i.e. the monomer, the crosslinker and the polymerization conditions. The relative reactivity of the exo- and endo-monomers was investigated using the 'Hnmr technique since the initiation and propagation steps of the polymerisations can be followed in detail by this technique. The results showed that the polymerisations are living and the exo-isomer is more reactive than endo-isomer. A wider range of polymers can be prepared from solution polymerisation as compared to bulk polymerisation. The polymers derived from solid monomers, the monofunctional monomer with short N-alkyl pendant groups and all the difunctional monomers, could be prepared more easily in solution than in bulk polymerisation. The endo-monomer and the monofunctional monomer with long N-alkyl pendant group showed very low reactivity and were not suitable for ROMP in bulk but underwent solution polymerisation. It was found that the thermal properties of the linear polymers depend upon the amount of each monomer isomer incorporated into the polymer chain and the ength of the N-alkyl pendant groups. All linear polymers are soluble in chlorinated solvents from which clear films can be cast. The work described establishes conditions for production of fully crosslinked solids with only traces of the sol fraction.

Thesis advisor: Amir H. Hoveyda / Chapter 1. Through the use of quantum theory of atoms in molecules (QTAIM) the similarities and differences between transition metal complexes ligated by phosphines and N-heterocyclic carbenes (NHC) were elucidated. Among the key findings, the phosphines were identified as stronger charge donors than NHCs; however, the latter class of ligands exhibits a weaker p-accepting character than the former. Furthermore, Tolman electronic parameter (TEP) was determined to be an inadequate gauge for the total electron donating ability of phosphines and NHCs; rather TEP can serve as a measurement of population of dp set of orbitals of a metal center in question. Computational and experimental studies of the mechanism of NHC-catalyzed boron and silicon addition to a,ß-unsaturated carbonyls reactions were carried out. Through the use of radical traps the mechanisms involving homolytic cleavage of B-B or B-Si bonds were ruled out. Computational (DFT) studies of the mechanism identified two pathways: (1) direct activation of diboron or borosilyl reagents through coordination of NHC to the B atom, (2) net oxidative addition of the diboron or borosilyl reagents to the carbon (II) of the NHC. The insights gained from the aforementioned studies were employed to rationalize the observed lack of reactivity of NHC-activated diboron complexes in the presence of aldehydes. Chapter 2. New C(1)-symmetric chiral monodentate N-heterocyclic carbenes were prepared, and corresponding chiral Ru-carbene complexes were synthesized. These complexes were employed to gain empirical understanding of factors that govern stereoselectivity in Ru-catalyzed enantioselective olefin ring-closing metathesis. The data thus obtained was employed to infer that syn-to-NHC reaction pathways are competitive and non-selective. One plausible mechanism, through which syn-to-NHC pathways can be accessed, involves Berry pseudorotations. Through the use of stereogenic-at-Ru complexes diastereomeric Ru-carbenes were isolated (silica gel chromatography) and spectroscopically characterized in solution phase. The diastereomeric Ru-carbenes were found to undergo non-metathesis stereomutations at Ru center, thereby providing additional support for the above hypothesis regarding accessibility of syn-to-NHC olefin metathesis pathways. Non-metathesis stereomutation at Ru was found to be accelerated in the presence of protic additives, suggesting the plausibility of hydrogen bonding between the acidic proton and the X-type ligands on Ru. Occurrence of hydrogen bonding was corroborated through the use of chiral allylic alcohols in Ru-catalyzed diastereoselective ring-opening/cross metathesis, which was developed into a versatile method for highly diastereoselective functionalization of terminal olefins. / Thesis (PhD) — Boston College, 2011. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

The first steps towards the long term objective of building entirely synthetic organic/inorganic composite materials in a biomimetic manner have been achieved. Following an introduction and discussion of the background to the work (Chapter 1), the syntheses and characterisation of various molecular weights of both poly(exo, exo-1,4-cyclopentenylene-5,6-ethylidene-2,3-sodium dicarboxylate) and poly(exo,endo-l,4-cyclopentenylene-5,6-ethylidene-2,3- sodium dicarboxylate) and model compounds of their repeat units have been described (Chapters 2 and 4). These compounds were used as additives in the crystallisation of CaCO(_3) from supersaturated aqueous solutions of Ca(HC0(_3))(_2) (Chapters 3 and 5). The work described in Chapter 3 showed that the diacid model compounds used as additives controlled the morphology of calcite crystals grown from supersaturated solutions of Ca(HCO(_3))(_2) over a large range of concentrations of model compound; [Ca(^2+)]: [model compound] 10 to 1000:1. The polymers of these monomers appeared to give the same type of crystal morphology as the isolated model repeat units, however, modification was observed on only one face of the CaCO(_3) crystals. This observation, and the relatively small crystal size distributions measured, indicated that the calcite crystallisation was nucleated beneath the polymer films at the truncated modified face and growth continued down into the solution.

Thesis (Ph. D.)--Ohio State University, 2004. / Title from first page of PDF file. Document formatted into pages; contains xviii, 228 p.; also includes graphics. Includes bibliographical references (p. 128-137).