Laurel Schafer

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This thesis examines the use of N-heterocyclic carbene ligands on Pt metal centers. Reactivity of chelated N-heterocyclic carbene ligands on Pt centers was studied in terms of oxidative addition, reductive elimination, isomerization, and ligand transfer reactions with an emphasis on carbon-halogen (C-X, X = Cl, Br, and I) bond reductive elimination. In Chapter 1, the research progress in the Love group in terms of carbon-halogen bond activation and methane functionalization is discussed. Chapter 2 describes the investigation of the mechanism of intermolecular oxidative addition of aryl halides to Pt(II) alkyl complexes. Pt(IV) phenyl complexes are successfully detected by 1H and NOESY NMR spectroscopy which provides experimental support for a concerted mechanism. Unusual selective reductive elimination of Csp³-I vs Csp²-Csp³ and Csp³-Csp³ bond is also observed. Computational methods support the experimental work.In Chapter 3, selective reductive elimination of Csp³-X (X = Cl, Br, and I) vs Csp³-Csp³ bond from isolated Pt(IV) complexes is discussed. Pt(IV) complexes are synthesized by oxidative addition of MeI, which exhibit an equilibrium with Pt(II) by oxidative addition and reductive elimination of MeI. Selective Csp³-I vs Csp³-Csp³ bond reductive elimination is observed in an (NHC)PtMe₂I₂ complex (NHC = N-heterocyclic carbene). Additionally, Csp³-Cl and Csp³-Br bond reductive elimination is observed in competitive with Csp³-I reductive elimination via initial isomerization. Computational methods are employed, that support the experimental work. In Chapter 4, reactivity of an anionic Pt(IV) complex is discussed in terms of imidazolium salt activation and NHC transfer. In an attempt to study the reactivity of cyclometalated Pt(IV) complexes, a cyclometalated (NHC)Pt(IV)Cl complex was synthesized by activation of imidazolium salt with a chloride arm, followed by oxidative addition of the Csp3-Cl bond. In contrast, the reaction occurs initially at the Csp³-Br position of the imidazolium salt in the reaction of Pt(II) with the Br analogous imidazolium salt. As a result, a novel anionic Pt(IV) complex stabilized by the bromide ion of imidazolium salt was isolated. Furthermore, intramolecular NHC transfer is observed from Pt(II) to Pt(IV) centers upon the reaction of the anionic Pt(IV) with additional Pt(II) precursor.

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The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.

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The full abstract for this thesis is available in the body of the thesis, and will be available when the embargo expires.

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This thesis describes the exploration of 1,3-N,O-chelated early-transition metals and their applications in diverse catalytic reactions. While cyclopentadienyl-ligated metal complexes and their derivatives are highly robust and have found extensive catalytic applications in industry, their robustness limits their ability to act cooperatively with the metal centre to promote new and challenging transformations. In addition, the multi-step synthetic routes required to access modified cyclopentadienyl derivatives hinder tuning of the steric and electronic properties as needed. 1,3-N,O-chelating ligands are complementary to cyclopentadienyl ligands as a result of their highly modular syntheses and unsymmetrical donor properties, leading to flexible coordination modes, hemilability, and potential for metal-ligand cooperativity. However, 1,3-N,O-chelating ligands are comparatively underexplored despite promising recent advances in catalysis.Chapter 2 describes the use of zirconium ureate complexes for the catalytic hydroamination of 2-vinylpyridine. Stoichiometric and mechanistic studies revealed that the reaction with 2-vinylpyridine proceeds through an aza-Michael mechanism, where the C−N bond forming step is reversible and can be directly observed by variable temperature 1H NMR spectroscopy. In Chapter 3, these zirconium ureate complexes were investigated for their reactivity in hydroaminoalkylation. This led to the discovery of the first catalytic example of hydroaminoalkylation with alkyne substrates to directly access allylic amines. Stoichiometric and mechanistic studies suggest that the open coordination sphere of the zirconium catalyst aids in promoting the challenging reaction steps necessary for catalytic turnover.Chapter 4 investigates the coordination chemistry and reactivity of vanadium pyridonate complexes, which were previously unexplored. These compounds can be made easily via protonolysis of amido or organometallic starting materials, as is the case for other early-transition metal pyridonates. Vanadium(IV) pyridonates were found to undergo reduction to vanadium(III) in some cases, and mechanistic studies found that the released alkylamine during protonolysis was acting as the reductant. These compounds also showed hemilability, potential for metal-ligand cooperativity, and a tendency to aggregate. Chapter 5 then discusses the application of vanadium pyridonate complexes in the catalytic reductive coupling of alcohols. Mechanistic studies showed that bimetallic intermediates were involved, providing complementary experimental evidence for the mechanism proposed by DFT in a reported monometallic catalyst system.

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Alkyltantalum precatalysts for intermolecular hydroaminoalkylation reactions between alkene and amine substrates are explored to gain insight into catalyst structure/activity relationships and to develop new methods for the regioselective and diastereoselective synthesis of amines and N-heterocycles. This thesis addressed significant challenges with widespread adoption of hydroaminoalkylation towards synthesizing products that display concrete applications in agricultural or pharmaceutical industries.First, we synthesized alkyltantalum starting materials and combined them with new ureate ligand salts for in situ catalyst mixtures that display promising reaction rates. Substrate scope in this section emphasized reactivity using switchable ureate salts for either terminal or internal alkenes while maintaining chemoselectivity with diene substrates. We then probed reaction scope changes that resulted from varying ligand steric and electronic factors. We extended this to study chiral cyclic ureate ligands to attempt enantioselective catalysis, these ligands resulted in poor ee’s, but presented unprecedented reactivity with challenging aliphatic amine substrates. Comparative hydroaminoalkylation reactivity with different Ta halides revealed that a brominated Ta started material is slightly more reactive than its chlorinated counterpart, while a fluorinated complex was not active at all.Catalysis with a new chiral ureate salt accomplished highly chemo- and regioselective C- C bond formation between substituted N-methylanilines and either limonene or pinene. We confirmed that hydroaminoalkylation does not racemize allylic stereocentres and can be selective for terminal alkenes. Further, pinene-containing products were consistently generated with high diastereoselectivity. All products were isolated using a simple filtration protocol.iiiThe catalyst system highlighted towards the end of this thesis was the first generally reactive hydroaminoalkylation system. Reactivity was excellent with aromatic or aliphatic amines, terminal or internal alkenes, and most importantly saturated N-heterocycles. Exploring substrate scope with these N-heterocycles resulted in consistently good yields, with good regio- and diastereoselectivity when unactivated alkene partners are used. However, additional data highlighted the linear dependence of regioisomer product ratios as a function of alkene electronic factors when combining piperidine with styrene partners. This discovery of substrate-controlled product selectivity allowed for only linear product to be obtained in select cases. Final results applied N-heterocycle reactivity to a two-step, one-pot catalytic, regiodivergent synthesis of indolizine and quinolizine alkaloids.

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This thesis focuses on investigating a bisamidate bisamido titanium complex as a pre-catalyst for the hydroamination of alkynes with primary amines. It begins with revealing the reaction mechanism using both theoretical and experimental tools. Next are efforts to extend the use of this catalyst for the synthesis of interesting functional materials and exploring its reactivity with α-heteroatom-substituted alkynes.Computational studies were performed to understand the high reactivity and regioselectivity of the titanium pre-catalyst, which could not be fully answered previously. The hemilabile amidate ligand was found to play a key role by both creating the right geometric environment to lower the transition state energies and to promote hydrogen bonding to allow metal-ligand cooperativity. Experiments were designed and conducted to test the computationally proposed mechanism.Conjugated enamine small molecules and polymers were successfully prepared using titanium-catalyzed hydroamination, and more importantly isolated as characterizable functional materials. They exhibit interesting photophysical properties including emission wavelengths and fluorescent quantum yields that are tunable with substituent modification. Moreover, computational analysis was found to be precise and useful in predicting and designing conjugated enamines as emissive materials. Early stage investigation of the synthesis of multi-broron-nitrogen-substituted polycyclic systems from conjugated enamines was presented together with their interesting photophysical properties.The first example of catalytic hydroamination of α-phosphino alkynes was achieved with the same titanium pre-catalyst. Phosphino enamines/imines and β-aminophosphines are important phosphorous-nitrogen-containing ligands. These compounds could be prepared easily with good functional group tolerance, high reactivity and high regioselectivity. The synthesis of nitrogen-phosphorous-nitrogen (NPN) type compounds and complexation using in situ generated ligands were found to be a successful route to prepare metal-NPN complexes. Additionally, an iron bisenamido complex was prepared via a sequential hydroamination-salt metathesis, and showed catalytic reactivity in ammonia borane dehydrogenation.Hydroamination of copper acetylide was successfully achieved with the titanium pre-catalyst as one of the few examples of metal acetylide hydroamination. Copper enamide product was isolated at almost quantitative yield and its structure was characterized. Mechanistic studies showed the reaction is a direct functionalization of the acetylide moiety by the [2+2] cycloaddition mechanism, which was supported by further kinetic and isotope competition studies.

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This thesis examines the use of hemi-labile amidate and ureate ligands on nickel metal centers in their (+1) and (+2) oxidation states. These 1,3-N,O-chelating ligands were studied both for their coordination chemistry on nickel and their propensity to undergo bond activations, specifically with carbon-hydrogen bonds. In Chapter 1 we discuss the mechanisms of C-H bond activation for nickel centers of different oxidation states. We highlight important works for each oxidation state, with a focus on computational and mechanistic work. The Chapter is broken down by oxidation state. In Chapter 2, we investigate the mechanism of Ni(II) C(sp³)-H bond activation. Using ureas as model substrates, we map the rates of C-H bond activation at Ni(II). We also characterize the nickellated products and investigate the role of additives on the rates of reaction. Comparisons to computational data from the literature are made where appropriate. In Chapter 3 we discuss amides as ligands for low-coordinate Ni(I) organometallics. Using a variety of ligands, we show that substitution of the ligand at both the nitrogen and the carbon backbone dramatically affects the binding mode at Ni(I). We also discuss reactivity with radical species and investigate the mechanism of disproportionation of these complexes. In Chapter 4 we discuss a new method for nickel catalyzed cyanation of aryl chlorides using a simple protocol. The reaction runs at room temperature and is among the mildest conditions to date. We show that XantPhos ligands are the best ligands to this end.

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The research presented in this thesis focuses on the development of practical methods for the early transition metal-catalyzed synthesis of amines. The primary focus of this thesis is the development of in-situ generated tantalum catalyst systems for the intermolecular hydroaminoalkylation of alkenes with amines. The intramolecular hydroamination of aminoalkynes followed by asymmetric transfer hydrogenation for the synthesis of chiral 1,4-benzoxazines was also developed. The substrate scope and synthetic utility of these reactions is presented herein.Initial efforts to expand the synthetic utility of hydroaminoalkylation focused on the use of a previously reported phosphoramidate tantalum methyl complex as a catalyst for the hydroaminoalkylation of norbornadiene to produce amine-containing monomers. The optimization of this reaction demonstrated key challenges in the use of hydroaminoalkylation as a synthetic tool. To address these challenges, methods for the in-situ generation of hydroaminoalkylation catalysts were developed. The generation of a pyridonate tantalum dimethylamido catalyst in-situ allowed for a robust catalyst that exhibited an unprecedented substrate scope. Attempts to further probe the reaction through modifying the electronic properties of the pyridonate ligand were unsuccessful. Products accessible from this catalyst system were further reacted to generate poly-methylated piperidines that would be difficult to synthesize through traditional methods.A second in-situ method utilizes tantalum pentafluoride, which is more robust than previously utilized tantalum precursors, to generate a hydroaminoalkylation catalyst in-situ. The substrate scope of this system was explored, and further reactions allowed for the synthesis of1,2,3,4-tetrahydroquinolines. The generation of this catalyst was studied through NMR spectroscopy. The stability of tantalum pentafluoride towards storage in ambient conditions was also studied, showing that while it could not be stored in a non-inert atmosphere, it could be handled in ambient conditions without significant loss of reactivity.Chiral 1,4-benzoxazines are an important class of compounds that form the core of many industrially relevant compounds. By utilizing a previously reported method for the asymmetric synthesis of morpholines through sequential hydroamination/asymmetric transfer hydrogenation, a variety of chiral 1,4-benzoxazines can be synthesized from readily accessible 2-aminophenyl propargyl ethers. While the synthesis suffers from poor yields, the method achieves moderate to good enantiomeric excesses and demonstrates improved step-efficiency.

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This thesis focuses on two distinct methods which were developed to access both a series of diheteroarylamides and a series of primary and secondary amines with a tertiary α-carbon. Crucial to the methods development for their synthesis was the use of N-silylated amines. The diheteroarylamides served as structural alternatives to a reference diheteroarylamide which showed potency against HIV-infected cells and the resulting primary and secondary amines were used as precursors to heterocyclic derivatives.In Chapter 1, an introduction on the catalytic synthesis and chemistry of the N-silylated amines is presented. Modern catalytic reactions to access N-silylamines and the type of transformations the resulting N-silylated amines can be engaged in are discussed.In Chapter 2, the value of N-silylated amines is highlighted with their use in amide bond formation of diheteroarylamides derived from electron deficient amines. The negative charge unveiled upon the desilylation of the above amines is a necessity for them to be engaged in the amidation reaction.In Chapter 3, the focus is centered on secondary N-silylated α-arylated amines which are used as substrates in zirconium catalyzed hydroaminoalkylation of alkenes to access primary α-arylated amines with a tertiary center on the α to the nitrogen carbon. Efforts to cyclize the resulting primary amines with the goal to access relevant heterocycles in organic and pharmaceutical chemistry are presented.In Chapter 4, N-aryl and N-alkylamines with a secondary α-carbon are used as substrates in zirconium catalyzed hydroaminoalkylation of alkenes to afford secondary α-arylated amines with a tertiary α to the nitrogen carbon. In analogy with the primary amines, some of the resulting secondary amines can further be cyclized into heterocyclic derivatives.Chapter 5 provides a summary and describes the future direction the two methods presented in Chapter 2 and 3&4 can take. For Chapter 2, the ongoing synthesis of diheteroarylamides will serve as a platform for the identification of the interactions with their target. For Chapters 3&4, there is space for the methodology improvement to control both regio- and diastereoselectivity in the resulting compounds. Further strategies on how to construct heterocycles with the resulting amines are discussed.

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The use of early transition metal complexes bearing N,O-chelating ligands for the preparation of functional materials is described within. The two central reactions explored are the hydroaminoalkylation of alkenes and the ring-opening polymerization of cyclic esters. To understand the key features of hydroaminoalkylation towards the design of more efficient catalysts, computational investigations using DFT have been used to develop a theoretical model of the catalytic cycle. The use of a sterically bulky, electron withdrawing amidate ligand leads to the formation of electrophilic metal centres that possess a plane of favorable reactivity trans to the amidate ligand. The steric bulk of the amidate ligand lowers the energy barrier to form catalytically active tantallaziridine species; however, it may also relieve steric congestion by accessing κ¹ bonding modes throughout the catalytic cycle. In the computed cycle, protonolysis of the 5-membered metallacycle is the turnover-limiting step and points toward a key area for optimizing reactivity through catalyst design. N,O-chelating pyridonate ligands are used with tantalum to form highly active hydroaminoalkylation catalysts for the challenging alkylation of cyclic diene substrates. The resulting amino-norbornene and amino-cyclooctene products are then polymerized using ring-opening metathesis polymerization to prepare polyolefins containing pendant amine groups. The viscoelastic characterization of these materials is conducted by melt rheology and reveals profound and surprising physical properties that result from the association of polymer chains by dynamic hydrogen-bonding. Reduction of the polymer backbone gives saturated polymers to yield pendant amine-functionalized polyethylene analogs. These materials show interesting physical properties, including self-healing and adhesion to poly(tetrafluoroethylene).Titanium pyridonates are used to conduct the ring-opening polymerization of cyclic esters. The modification of the ligand environment through changing the number of pyridonates or the nature of the nucleophilic ligand does not dramatically affect the resulting polymers obtained. These initiators are also used to combine rac-lactide and ε-caprolactone into random and block copolymers. A stoichiometric reaction with methylene lactide and the ruthenium starting material RuCl₂(PPh₃)₃ is used to prepare a novel ring-opened ruthenium carboxylate species. This product results from the nucleophilic attack of a liberated triphenylphosphine ligand from the starting complex.

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Associating polymers, consisting of relatively small functional groups capable of forming reversible physical associations, represent an important class of materials since they can be used in stimuli-responsive systems. They have found numerous applications in self-healing systems, and they can be used as shape memory polymers and biomaterials. Their complex behavior depends on the delicate interplay between the chemistry of functional groups and polymer dynamics. Therefore, it is essential to understand the physics of these complicated networks to exploit their full potential for important/innovative applications.Two classes of associating polymers, namely ion-containing polymers (ionomers), and hydrogen bonding polymers, were studied. Using a rotational rheometer and the Sentmanat extensional fixture, a full rheological characterization of several commercial ionomers and a series of novel amine-containing polynorbornenes and polycyclooctenes was conducted. Emphasis has been placed on the distribution of the relaxation times to identify the characteristics times such as reptation, Rouse times and the characteristic lifetime of the ionic and hydrogen bonding associations. These characteristic relaxation times were related to the structure of these polymers using developed scaling theories.Complete removal of ions was performed to produce copolymers in order to study the relative effects of ionic associations. It was demonstrated that ionic interactions increase the linear viscoelastic moduli and the viscosity by up to an order of magnitude and cause significant strain hardening effects in uniaxial extension. Similarly, for the novel hydrogen bonding polymers, the reversible associations significantly increase the rheological properties and thus delay their relaxation, causing chains to strain-harden before failure. Additionally, it was discovered that the amine-containing polymers exhibit outstanding self-healing properties. Optimal, fast self-healing response was achieved by varying the molecular weight and structure of these materials.Finally, the capillary flow of several commercial ionomers was studied both experimentally and numerically. The excess pressure drop due to entry, the effect of pressure on viscosity, and the possible slip effects on the capillary data analysis were examined. Rheological data were successfully fitted to a viscoelastic model developed by Kaye, Bernstein, Kearsley, and Zapas, (known as the K-BKZ model) to perform relevant capillary flow simulations.

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This thesis details the development of transition-metal complexes that are utilized as precatalysts for catalytic hydroaminoalkylation chemistry. Hydroaminoalkylation is the activation of an α-C(sp³)–H of an amine, and subsequent addition across a C–C unsaturation. This results in α-alkylated amines in a 100% atom-economical reaction, while avoiding amine protection/deprotection strategies.A series of 2-pyridonate chloro tris(dimethylamido) tantalum complexes have been synthesized and tested for the hydroaminoalkylation of alkenes with secondary amines. These complexes were found to exhibit high reactivity for a broad range of internal alkene substrates and represent the first, general hydroaminoalkylation of cyclic and linear internal alkenes that occurs without isomerization of the C=C double bond. Further study supports the assertion that minimized steric parameters of the 2-pyridonate and chloro ligands allow for reactivity with sterically demanding internal alkenes. Kinetic studies and deuterium labeling experiments reveal a complex kinetic profile and provide evidence for off-cycle equilibria that dominate catalytic activity.Complementary to this work, an alternative 1,3-N,O-chelating phosphoramidate ligand framework was explored to synthesize Nb complexes for hydroaminoalkylation. A variety of monophosphoramidate tetrakis(dimethylamido) Nb complexes were synthesized, as well as bis(phosphoramidate) niobaziridines, which are proposed as intermediates for the hydroaminoalkylation mechanism. The optimal precatalyst system was found to be an in situ preparation of 2:1 phosphoramide:Nb(NMe₂)₅. This offers comparable results to analogous phosphoramidate Ta complexes, but with a significantly different phosphoramidate ligand set. New cationic complexes of Ru, Rh, and Ir were synthesized featuring a bidentate κ²- P,N- phosphino-2-pyridonate ligand. These complexes were not viable precatalysts for hydroaminoalkylation, but were found to promote the stoichiometric dehydrogenation of amines to generate cationic metal hydrides. Analogous cationic complexes of 1,3-N,O-chelating 2- pyridonate complexes were prepared in situ and were found to catalyzed the reaction of dibenzylamine to tribenzylamine. A 2-pyridonate Ru complex was found to catalyze the dehydrogenation of benzylamine to the corresponding imine in the presence of isoprene, which acted as the hydrogen acceptor. Attempted hydroaminoalkylation reactions with non-arene supported 2-pyridonate complexes did not result in catalysis. These results provide insight into the use of late-transition metal complexes in amine activation and reactivity.

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This thesis discusses the synthesis and characterization of group 6 complexes that have metal element multiple bonds and 1,3-N,O-donor ligands. Furthermore, the evaluation of the metal-ligand interactions, including hemilability and metal-ligand cooperativity in E-H bond activation processes (where E=C or N), of the 1,3-N,O-donor ligands that resulted in reactivity of the metal element multiple bonds is reported. The 1,3-N,O-donor ligands in this thesis include amidates and pyridonates. The 1,3-N,O-donor ligands were installed on group 6 metals directly from the 1,3-N,O-proligands or as deprotonated sodium salts of the 1,3-N,O-proligands, by protonolysis or salt metathesis reactions respectively. Complexes such as di(1,3-N,O-chelate)bis(t-butylimido)tungsten and di(1,3-N,O-chelate)bis(dimethylamido)molybdenum, were synthesized by protonolysis reactions in chapters 2 and 4 respectively. In chapter 3 di(1,3-N,O-ligated)(neopentylidene)(oxo)tungsten complexes were synthesized by both protonolysis and salt metathesis reactions. These group 6 complexes with 1,3-N,O-donor ligands were characterized by single crystal X-ray diffraction, and in solution by multinuclear NMR spectroscopies, among other analytical methods. The solid-state molecular structures showed κ²-N,O, κ¹-O and µ²-N,O bonding modes, highlighting the flexibility of the 1,3-N,O-donor ligands. Solution NMR spectroscopy showed fluxional 1,3-N,O-donor ligands in all complexes at elevated temperatures, further highlighting the hemilability of these ligands. Throughout this thesis, pyridonate ligands showed more dynamic hemilability relative to amidate ligands. In chapter 2 pyridonate ligands were observed to have κ²-N,O, κ¹-O and µ²-N,O bonding modes in the solid state, whereas amidate ligands where exclusively bound in a κ²-N,O in the solid state. Variable temperature ¹H-NMR spectroscopy demonstrated that pyridonate ligands were fluxional at temperatures above -40 °C, whereas amidate ligands were fluxional at elevated temperatures (>60 °C). The steric parameters of 1,3-N,O-donor ligands influence how the ligands prefer to bond to the metal. Furthermore the steric demand also influences the hemilability of the 1,3-N,O-donor ligands. The differences in the electronic parameters between amidate and pyridonate ligands influences their hemilability, where pyridonates exhibit more dynamic hemilability in part due to the aryloxy imine motif. The metal-ligand cooperativity of the hemilabile 1,3-N,O-donor ligands towards E-H bond activations (where E=C or N) is reported in this thesis and applications of these processes are discussed.

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This thesis details the development of sequential intermolecular hydroamination of alkynes with amines followed by other reactions for the synthesis nitrogen-containing compounds, such as amines and heterocycles. The main feature of this thesis is the use of a bis(amidate)bis(amido)titanium complex, also known as the Schafer titanium catalyst, for the catalytic intermolecular hydroamination of terminal and internal alkynes.The catalytic synthesis of linear secondary amines using the Schafer titanium catalyst was accomplished through an intermolecular hydroamination of terminal alkynes followed by a Pd/C hydrogenation. The clean formation of products allowed for a facile synthesis and isolation of 23 examples of secondary amines in yields of 33-99%. The developed methodology allows for the synthesis of a variety of secondary amines containing aryl or alkyl substituents within a few hours and without the need for column chromatography.The selective anti-Markovnikov hydroamination of alkynes and ammonia remains a challenge. The first example of a hydroamination reaction with N-silylamine as an ammonia surrogate is disclosed in this thesis. Synthesis of anhydrous N-silylamine was accomplished using gaseous ammonia and tert-butyldimethylchlorosilane, which was then reacted with a variety of terminal and internal alkynes, leading to the synthesis of 25 examples of N- silylenamines in yields of 54-99%. The synthesis of primary amines (9 examples) was also accomplished upon treatment of the reaction mixture with palladium on carbon (Pd/C) and H₂. The isolation and characterization of key organometallic titanium-imido complexes was performed to probe the mechanism of the hydroamination reaction. Computational studies were also performed to study the preference of the N-silylenamine over the N-silylimine tautomer.Upon the remark that N-silylenamines were observed exclusively in the majority of cases, it was reasoned that such synthons could be used towards the synthesis of pyridines. Following the reported hydroamination reaction, a large variety of pyridines were formed with the addition of α,β-unsaturated followed by an oxidation event. This methodology allowed for the synthesis of 47 examples of mono-, di-, tri-, tetra-, and penta-substituted pyridines in yields of 11-96%.

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This thesis explores the use of 1,3-N,O chelating ligands, amidates and phosphoramidates as ligands for rhodium and iridium in the +1 and +3 oxidation states. Toward this end, a series of novel group 9 complexes were prepared, characterized, and employed for cooperative small molecule activation and element-hydrogen (E-H) bond cleavage reactions. In Chapter 1, amides and phosphoramides are introduced as ligands for late transition metals. In particular, it is highlighted that such ligands have traditionally been used to form early transition metal and lanthanide N,O-chelated complexes, with the late transition metal chemistry being highly underdeveloped. In Chapter 2, the fundamental reactivity of rhodium(I) complexes having amidate ancillary ligands is presented including catalytic oxygen atom transfer using O₂ – the products of such reactions: η²-O₂ complexes were characterized using NMR spectroscopy and density functional theory (DFT). Chapter 3 details the use of 1,3-N,O chelated complexes of monovalent Rh(I) and Ir(I) for the controlled capture of HBCy₂, providing six-membered genuine metallaheterocycles bearing a δ-B-H agostic interaction, which can be employed for chemoselective boron transfer reactions. In this chapter, the inclination of this ligand class to change the chemoselectivity of HBCy₂ hydroboration toward carbonyl-containing substrates (in the presence of an alkene) is provided. Chapter 4 examines the preparation of the first unsaturated Cp*Ir(III) (Cp* = C₅Me₅) phosphoramidate complex for use in element-hydrogen (E-H) bond activation (E = H, C, Si, B). The syntheses of coordinatively unsaturated (E)-vinyloxy Cp*Ir(III) complexes, which are prepared from regioselective 1-alkyne C-H bond activation and O-phosphoramidation is discussed. This regioselectivity is completely inverted from that of free phosphoramidates, which undergo preferential N-alkylation. Finally, we illustrate how aminoborane (H₂B=NR₂) B-N bond rotation can be accessed using joint metal-ligand stabilization between Ir and a phosphoramidate coligand. All complexes were rigorously characterized using NMR spectroscopy, X-ray diffraction, as well as by DFT. Chapter 5 surmises a new protocol for rhodium-mediated ethylene amination (nitrogen-carbon bond formation) using diazenes (RN=NR) as the N-atom source. This work provides a “proof-of-principle” for the functionalization of simple C₂-synthons using easily handled nitrogen-sources, providing rhoda(III)heterocycles, which undergo [Rh]-N bond protonolysis to provide ethyl-substituted hydrazine complexes.

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The research presented in this thesis highlights the utility of N,O-chelated complexes of early transition metals for the catalytic synthesis of amines. Two atom economic transformations to make carbon-carbon and carbon-nitrogen bonds, hydroaminoalkylation and hydroamination, were investigated. A significant expansion of the substrate scope of a pre-established catalytic system is presented, and a variety of novel titanium precatalysts were developed and screened for catalytic activity. The products of hydroaminoalkylation were employed as monomers for ring-opening metathesis polymerization using known ruthenium-based catalysts. These amine-containing polymers show interesting rheological behavior attributed to the presence of hydrogen bonding interactions. The substrate scope of a previously reported tantalum phosphoramidate complex capable of room temperature reactivity was expanded to include a solvent-free protocol. This methodology was shown to afford amine products in comparable or greater yields than the related diluted reactions. Titanium metal was investigated as an alternative to tantalum-based precatalysts. A family of mono-, di-, and tri-substituted phosphoramidate complexes was presented, with mono-phosphoramidates outperforming the others in the catalytic synthesis of amines, despite being susceptible to unwanted ligand redistribution reactions. The selective mono-alkylation of cyclic diene substrates was shown to generate strained alkene products suitable for use in ring-opening metathesis polymerization. Despite having unsaturated, Lewis-basic moieties, these monomers were polymerized to generate a variety of viscoelastic homopolymers bearing substituted aryl-amines with tunable hydrogen bonding potential. Thermal and rheological analysis revealed behaviours characteristic of hydrogen bonding, such as increased glass transition temperatures, and viscosity dependent on molecular weight and amine substitution. An expansion of the monomers amenable to polymerization was presented, and a variety of copolymeric structures were synthesized. Efforts focused on pairing amine-containing monomers with those of commodity plastics, such as norbornene. Excellent control over monomer incorporation was achieved in most cases. Preliminary investigations into useful applications of these novel polymers were presented and include anti-microbial materials, agents for sequestering metal ions, and compatibilizers for polymer blends. These preliminary experimental results show promise and future efforts will focus on realizing the full potential of these unique materials.

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The research presented in this thesis emphasizes the versatility and utility of N,O-chelated early transition metals for the catalytic synthesis of -alkylated amines. Two major transformations were studied extensively in this work, hydroamination and hydroaminoalkylation. For both reactions, the synthetic utility and substrate scope has been expanded by the work presented herein. In the field of hydroamination, N-heterocycles with more than one heteroatom can now be synthesized using early transition metal catalysts from prochiral substrates. Hydroamination with a bis(amidate)bis(amido) complex of titanium of ether-containing aminoalkyne substrates yield cyclic imines, which are subsequently reduced via asymmetric transfer hydrogenation using the Noyori-Ikariya catalyst, RuCl [(S,S)-Ts-DPEN] (η⁶-p-cymene). 3-Substituted morpholines are synthesized using a one-pot sequential catalysis protocol, in good yields and high enantiomeric excesses. Substrate scope investigations reveal that high enantioselectivities in the asymmetric transfer hydrogenation reaction arise from key hydrogen bonding interactions between the oxygen heteroatom of the ether-containing cyclic imine and the [(S,S)-Ts-DPEN] ligand of Noyori-Ikariya catalyst. This mechanistic insight informed the proposal that this synthetic strategy can be extended to other substrates containing functional groups with hydrogen bond acceptors. As such, 3-substituted piperazines are also prepared with high enantioselectivities using this one-pot protocol.Advances to the hydroaminoalkylation transformation have also been made with the first reported example of room temperature reactivity observed using a phosphoramidate-tantalum complex. The preparation and characterization of a series of N,O-chelated phosphoramidate-tantalum complexes is described. These complexes were easily synthesized from either Ta(NMe₂)₅ by protonolysis or a simple organometallic precursor, TaMe₃Cl₂, by salt metathesis. Reactivity towards catalytic hydroaminoalkylation was explored and the results highlight that the choice of tantalum starting material dramatically affects the reaction temperatures required for catalytic turnover. N,O-chelated phosphoramidate dimethylamido tantalum complexes showed reactivity occurred only at elevated temperatures (≥ 90 °C), whereas phosphoramidate-tantalum complexes derived from TaMe₃Cl₂ exhibited unprecedented catalytic activity at room temperature. Preliminary efforts indicate that there is potential for an asymmetric version of hydroaminoalkylation at room temperature. Chiral phosphoramidate-tantalum complexes were prepared and studied as the first examples of asymmetric hydroaminoalkylation reactions at room temperature.

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The work described in this thesis focuses on the development of pyridine-derived group 4 and 5 complexes for application in the catalytic synthesis of selectively substituted amines. Two different catalytic alkene hydrofunctionalization reactions were targeted: hydroamination and hydroaminoalkylation. Respectively, these transformations provide atom-economical strategies for the formation of new C–N and C–C bonds on amines, using simple alkenes as the alkylating agents. A series of bulky mono(2-aminopyridinate)tris(dimethylamido)titanium complexes with varying steric parameters were synthesized and explored for intramolecular hydroamination reactivity using aminoalkene substrates. A titanium catalyst capable of room-temperature hydroamination reactivity was identified for the synthesis of gem-disubstituted 5- and 6-membered-ring products. This catalyst has good breadth of reactivity, including the challenging 7-membered-azepane ring formation and hydroamination with internal alkenes. A catalytically active 2-aminopyridnate-supported imido titanium complex was prepared, and reactivity investigations of this complex suggest that this reaction proceeds via an intermediate imido [2+2] cycloaddition pathway. Various 3-substituted-2-pyridonate ligands were synthesized and examined as ancillary ligands for targeting chemoselectivity for intramolecular hydroaminoalkylation over hydroamination. Systematic ligand screening studies showed that bis(3-phenyl-2-pyridonate)bis(dimethylamido)titanium complex is selective for hydroaminoalkylation over hydroamination. This is the first catalyst that can selectively α-alkylate primary aminoalkenes to access both 5- and 6-membered-cycloalkylamines with good substrate-dependent diastereoselectivity. Mechanistic and stoichiometric experiments using this complex support the involvement of a bimetallic imido species in the reaction. Notably, a titanium(III) species was isolated during these investigations. Reliable synthesis of this titanium(III) complex and examination of its reactivity showed that it is not active for hydroaminoalkylation. Varying combinations of mixed 2-pyridonate/alkyl/amido/chloro tantalum complexes were targeted to expand the substrate scope for intermolecular hydroaminoalkylation. The synthesis of mono(2-pyridonate)/alkyl/chloro tantalum complex was unsuccessful. Instead, bis(2-pyridonate)tantalum alkyl complexes were formed. While these complexes showed hydroaminoalkylation reactivity for terminal alkenes, their thermal and light sensitivity presents difficulty for synthetic application. The design and synthesis of a mixed 2-pyridonate-Ta(NMe₂)₃Cl provided a sterically accessible metal center for the hydroaminoalkylation of sterically demanding disubstituted alkenes. This complex is the first effective precatalyst for the alpha-alkylation of unprotected secondary amines using unactivated (E)- and (Z)-internal alkenes without C=C bond isomerization.

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The use of titanium or zirconium amidate complexes as either reagents or catalysts for targeted applications is described herein. The investigation is focused on a novel class of zirconocene amidate hydride complexes primarily used for the hydrozirconation reaction and a previously disclosed bis(amidate) bis(amido) titanium complex for the regioselective alkyne hydroamination reaction. A novel class of zirconocene amidate hydride complexes is synthesized and characterized. The amidate binding mode is significantly influenced by sterics. A rare example of an equilibrium between the structural isomers where the amidate ligand adopts either the κ¹ O-bound or κ² is shown. Reaction of styrene with these complexes resulted in the formation of the branched insertion products, which is in contrast to the observed regioselectivity when the well-known Schwartz’s reagent is used. Asymmetric insertion was attempted with a complex bearing an amidate ligand with a stereocenter. Reactivity with other alkenes and phenylacetylene were explored. Under harsh reaction conditions, the zirconocene amidate hydride complexes undergo a halide exchange reaction with phenyl halides. A competition experiment suggests two separate mechanistic pathways for styrene insertion and halide exchange. A primary kinetic isotope effect suggests Zr─H cleavage is involved in the rate-determining step. Experimental evidence is consistent with a coordination-insertion mechanistic proposal. The synthetic utility of a previously reported bis(amidate) bis(amido) titanium complex for the regioselective alkyne hydroamination reaction is further explored. The reactivity and regioselectivity of hydroamination with benchmark substrates using this bis(amidate) titanium complex is directly compared to other titanium based hydroamination catalysts. The substrate scope of this bis(amidate) titanium hydroamination catalyst is extended to include more difficult substrates, such as protected propargyl alcohols. Modifications to the reaction protocol allow for facile bench-top use. The bis(amidate) titanium complex was applied to tandem sequential reactions featuring hydroamination to afford secondary amines, a primary amine and a substituted primary allylamine. This hydroamination catalyst is also used for the oligomerization of alkynylanilines. By tuning the alkynylaniline monomer, a soluble N-containing oligomer was synthesized, which shows a degree of conjugation. This bis(amidate) titanium hydroamination catalyst was employed to assemble a small library of aminoether compounds targeted as T-type calcium channel blockers.

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This is a study of early metal organometallic complexes for catalytic C-N and C-C bond formation using amines. The use of zirconium complexes as hydroamination catalysts is explored first. New axially-chiral bis(amide) and bis(urea) proligands are designed. Synthetic methods used to generate these compounds are described and X-ray crystallographic analysis of a bis(sulfonamide) establishes the absolute configuration of the chiral proligands. Installation of the new bis(amidate) and bis(ureate) ligands onto zirconium is undertaken and the structure of these complexes is examined in solution and, where possible, in the solid state. Where well-defined zirconium complexes can be obtained, those complexes are tested for their efficacy in enantioselective catalytic hydroamination. In the absence of well-defined zirconium complexes, an in situ catalyst generation protocol is employed. Catalysts featuring a bis(amidate) ligand derived from 2,2ʹ-diamino-6,6ʹ-dimethylbiphenyl achieve modest hydroamination activity with a primary aminoalkene at 110 °C, with enantiomeric excesses (ee’s) of up to 25%. Catalysts featuring a bis(amidate) ligand derived from 3,3ʹ,5,5ʹ-tetrabromo-2,2ʹ-diamino-6,6ʹ-dimethylbiphenyl display impressive reactivity with a primary aminoalkene, including room temperature hydroamination, with ee’s ranging from 52-55%. Catalysts featuring a bis(ureate) ligand derived from 2,2ʹ-diamino-6,6ʹ-dimethylbiphenyl are shown to be capable of cyclizing secondary aminoalkenes with ee’s up to 63%. Capillary electrophoresis is developed as a method to determine the ee of tertiary amine products. A kinetic study of a catalyst featuring a bis(amidate) ligand derived from 2,2ʹ-diamino-6,6ʹ-dimethylbiphenyl supports established mechanistic proposals for neutral group 4 hydroamination catalysts. Solid state molecular structures, combined with existing knowledge of bonding and catalytic reaction pathways, are used to propose models for how enantioselectivity is achieved through the use of different ligand frameworks.The use of known ligands in the formation of tantalum complexes for hydroaminoalkylation catalysis is then explored. Installation of such axially-chiral bis(amidate) ligands onto tantalum centres is undertaken and the structure of these complexes is examined in solution and, where possible, in the solid state. Catalytic testing reveals general competence of these catalysts for the hydroaminoalkylation reaction.

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The development of a synthetic approach to 2,5-unsymmetrically substituted piperazines from readily available terminal alkynes and amine substrates employing both intermolecular and intramolecular hydroamination methodologies developed in the Schafer group is reported in this thesis. The approach requires only three isolation/purification protocols. Firstly, regioselective intermolecular hydroamination in the presence of titanium bis(amidate) precatalyst is performed, followed by the one-pot addition of trimethylsilyl cyanide to the imine and subsequent displacement of the TMS group to obtain α-aminonitriles. Reduction of the α-aminonitriles is required to achieve the desired hydroamination precursors. The piperazine core is then completed by intramolecular diastereoselective hydroamination with the zirconium tethered bis(ureate) catalyst. The synthetic approach employed features two hydroamination reactions for the synthesis of these biologically active heterocycles. Synthesis of enantiopure piperazine was achieved via a chiral auxiliary-based approach; after the enantiopure aminonitrile was synthesized, subsequent reduction and enantiospecific intramolecular hydroamination with the zirconium tethered bis(ureate) catalyst were performed. The synthetic sequence thus developed illustrates the usefulness of inexpensive and low-toxicity group 4 amidate and ureate catalysts for the rapid synthesis of functionalized heterocycles suitable for further medicinal chemistry investigations.The screening of a series of novel unsymmetrically substituted piperazines for calcium channel blocking activity was performed. Potent N-type calcium channel blockers were discovered and a new trend in the development of piperazine medicinally relevant heterocycles was found. This contribution highlights a modular synthetic approach to the efficient preparation of previously unknown piperazines suitable for biological screening.In addition to 2,5-disubstituted piperazines, 2,5-disubstituted diazepanes were efficiently obtained on the basis of the developed strategy. Specific heterocyclic structural features in the 1H NMR spectra inspired us to propose a practical NMR-based method for revealing the relative stereochemical configuration of the synthesized heterocycles. Overall, this thesis covers different aspects of medicinal chemistry, green chemistry, synthetic chemistry and catalysis to provide conceptual and practical contributions to each of these branches of modern chemistry. Concepts and protocols developed in the course of this thesis can bring an important contribution to new approaches in drug discovery and our understanding of the application of hydroamination in synthetic chemistry.

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The synthesis, structure, and reactivity of early transition metal complexes containing(N,O)-chelating ancillary ligands are described. The ligands investigated include ureates,pyridonates, amidates, and sulfonamidates. These related ligands generate four-memberedmetallacycles when bound to the metal center in a κ²-(N,O) fashion. The zirconium and tantalumcomplexes have been examined in terms of their activity and selectivity as precatalyst systemsfor hydroamination or hydroaminoalkylation.A chiral cyclic ureate ligand has been synthesized from enantiopure L-valine forapplication in zirconium-catalyzed asymmetric hydroamination of aminoalkenes. Chiralzirconium complexes, prepared in situ from two equivalents of the urea proligand andtetrakis(dimethylamido) zirconium, promote the formation of pyrrolidines and piperidines in upto 12% ee. Isolation of an asymmetric bimetallic zirconium complex containing three bridgingureate ligands confirms that ligand redistribution occurs in solution and is most likelyresponsible for the low enantioselectivities.Mechanistic investigations focusing on the hydroaminoalkylation reactivity promoted bya bis(pyridonate) bis(dimethylamido) zirconium precatalyst expose a complex catalytic system insolution. Stoichiometric investigations reveal the formation of polymetallic complexes uponaddition of primary amines. The kinetic and stoichiometric investigations are most consistentwith a bimetallic catalytically active species.A series of mono(amidate) tantalum amido complexes with varying steric and electronicproperties have been synthesized via protonolysis. Solid-state and solution-phasecharacterization indicate that the amidate substituents influence the observed binding mode of the ligand. Salt metathesis and protonolysis routes to the synthesis of mixed tantalum chloro amidate complexes are investigated. Sulfonamide proligands react with pentakis(dimethylamido) tantalum to generate well-defined monomeric complexes containing a κ²-(N,O) bound sulfonamidate. The hemilabile (N,O)-chelating amidate ligands, which generate four-membered metallacycles, are the most active of the precatalysts examined for the intermolecular hydroaminoalkylation of terminal olefins with secondary amines.The substrate scope of a mono(amidate) tetrakis(dimethylamido) tantalum complex has been examined for the α-alkylation of unprotected piperidine, piperazine, and azepane N-heterocyclic amines. The lack of reactivity with pyrrolidine substrates is examined by quantum chemical calculations and isotopic labeling studies. Two (N,O)-chelating ureate ligands are also successful ancillary ligands for this transformation and, with a C₁-symmetric chiral ureate complex, enantioselective α-alkylation of piperidine is observed.

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The use of stoichiometric, catalytic and theoretical methods in the development of an early transition metal catalyst for the α-alkylation of amines is described herein. The investigation is primarily focused on a series of mono(amidate) complexes of tantalum with varying steric and electronic properties. The amidate binding mode and catalytic activity of these complexes is significantly influenced by sterics. Corresponding bis(amidate) complexes are less active as catalysts for the α-alkylation of amines but offers a platform to study the hemi-lability of amidate ligands as well as tantalaziridine formation in these systems. A model 5-membered metallacycle is synthesized and characterized.Isotopic labeling studies with the most active mono(amidate) precatalyst reveal off-cycle reactions and suggest that tantalaziridine formation is rapid and reversible. Preliminary kinetic investigations implicate alkene insertion as the turnover limiting step, consistent with stoichiometric investigations. In addition, the use of radical probes in ligand backbones and an alkene substrate contradicts a one electron mechanism.Quantum chemical calculations are used to develop a theoretical model of the proposed catalytic cycle. The hemi-lability of amidate ligands is highlighted with the optimization of both κ¹(O) and κ²(N,O) minima and transition states. Here, protonolysis is calculated to be the turnover limiting step with small changes in geometry having a significant effect on the potential energy surface. The unlikelihood of a radical mechanism is supported by the computations of triplet species. A survey of established steric parameters has been completed for asymmetric amidate ligands to be used as a predictive tool for catalyst design. The calculated values can be related to the catalytic activity of mono(amidate) and axially chiral tantalum precatalysts. Diamide and diurea proligands featuring a neutral chalcogen atom tether are installed on zirconium and tantalum. The zirconium species form well-defined κ⁴(N,N,O,O) complexes with fluxional behaviour observed for the tantalum species in solution. No evidence of bonding is observed between the chalcogen donor and any metal centre. Fundamental differences in the redox potentials for ligands and complexes are investigated using cyclic voltammetry. The tantalum complexes are found to catalyze the α-alkylation of amines with the zirconium species being competent precatalysts for hydroamination.

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The solution rheological properties and melt viscoelastic behaviour of a number of commercial and newly synthesized PCLs with different molecular characteristics was investigated using both rotational and extensional rheometry. The variation of zero-shear viscosity and relaxation spectrum with molecular weight were found to be in agreement with theories for linear polymers. The classic Wagner model was found to represent the rheology of all PCL polymers quite well. In addition, the PCL processing instabilities were studied by capillary extrusion. Sharkskin and gross melt fracture was observed for the high molecular weight PCL at different shear rates. The onset of melt fracture occurred at 0.2 MPa at temperatures higher than 115°C. Moreover, addition of 0.5 wt% of a polylactide (PLA) into the PCL eliminated or delayed the onset of melt fracture to higher shear rates. The thermodynamics and rheological behavior of PCL/PLA blends has been studied in an attempt to find ways to improve the mechanical properties of PCL. The effects of shear and heating rates on the determination of the phase separation boundary of the PCL/PLA blend system were studied in detail. The lower critical solution temperature (LCST) phase boundary for this system is shifted based on the frequency, heating rate and concentration of the components. Additionally, higher molecular weight amorphous PLA leads to phase separation boundary shifted to lower temperatures. Differential scanning calorimetry (DSC) thermograms of PCL/PLA blends exhibit separate melting peaks, which are indicative of immiscible structure at all compositions in agreement with the phase diagram. Scanning electron microscopy (SEM) images have shown droplet morphology of PCL into PLA matrix up to 40wt% of PCL. Above this concentration the co-continuous morphology starts to appear, which becomes again droplet morphology for blends with PCL concentration above 60wt%. The viscoelastic studies in the phase separated region have shown the enhancement of the elastic modulus of blends at small frequencies, which is a signature behavior of immiscible systems due to the presence of interface and interfacial tension contribution to the stress. Emulsion models were found to be successful in the prediction of viscoelastic behavior at the compositions which corresponds to droplet morphology.

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Yttrium complexes are highly attractive systems for use in catalysis due to their high activity, low cost, and low toxicity. The highly modular amidate ligand set allows for easy variation of steric and electronic properties and, therefore, the reactive metal complex. This thesis explores the synthesis of yttrium amidate complexes and their use as catalysts in a variety of catalytic transformations.Mono-, bis-, and tris(amidate) complexes of yttrium are highly active initiators for the ring-opening polymerization of rac-lactide, yielding PLA with high molecular weight and narrow polydispersity. Termination of this polymerization is proposed to occur through formation of cyclic PLA with large ring sizes, once the monomer is consumed. Reaction of additional monomer is, therefore, not possible, and the polymerization is not living.The mechanical properties of the poly(ε-caprolactone) synthesized using tris(amidate) complexes of yttrium were determined to be consistent with those of commercially available polymer samples. Rheological testing of prepared poly(ε-caprolactone) suggested the possible formation of polymers with long-chain branching. However, the formation of long-chain branching in the poly(ε-caprolactone), synthesized with the tris(amidate) complex containing the naphthyl substituent, could not be confirmed or wholly refuted based on traditional chemical analyses. One yttrium tris(amidate) complex was also found to initiate the ring-opening polymerization of ε-caprolactone and rac-lactide to form diblock PCL/PLA copolymers.The mono-, bis-, and tris(amidate) complexes of yttrium are also highly active catalysts in the mild amidation of aldehydes with amines. The tris(amidate) complexes were most active, catalyzing the reaction in as little as 5 minutes. The best-performing catalyst can mediate the amidation of alkyl or aryl aldehydes, as well as aryl primary amines and alkyl or aryl secondary amines. This catalyst is also the first example of a rare-earth catalyst capable of tolerating pivalaldehyde in this transformation.The aforementioned class of complexes has been proven to be effective in a number of catalytic transformations. The modular synthesis of the amidate ligand, as well as the facile synthesis of yttrium amidate complexes, provide an easy means for altering the steric and electronic properties of the resulting complexes and, therefore, are ideal for further catalyst development.

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A two-part study involving the synthesis and catalytic investigations of amidate complexes of early transition metals is described. In the first part, the substrate scope of an achiral bis(amidate) titanium hydroamination precatalyst has been broaden to include challenging substrates. This complex efficiently catalyzes the hydroamination of heteroatom-containing allenes with arylamines. Control experiments rule out allene-alkyne isomerization as a reaction pathway during this catalysis. The hydrohydrazination of a variety of alkynes with 1,1-disubstituted hydrazines also proceed efficiently in the presence of this precatalyst giving the anti-Markovnikov hydrazone products predominantly. These hydrazones have been transformed into substituted indoles by a one-pot tandem sequential hydroamination/ZnCl₂-mediated cyclization. Importantly, the bis(amidate) titanium precatalyst can be generated in situ for these reactions with no impact on the reactivity or selectivity of the complex.The second part of this thesis focuses on the synthesis, characterization, stability and catalytic investigations of chiral zirconium and tantalum complexes ligated with amidate ancillary ligands. Seven new axially chiral proligands have been synthesized and used for in situ generation of zirconium hydroamination precatalysts. These chiral complexes efficiently produce N-heterocycles in up to 94% isolated yield with ee reaching 74%. Preparative scale synthesis and characterization of the zirconium complexes revealed coordination geometry that is greatly influenced by the steric properties of the ligand. Bulky proligands produce monomeric complexes, wherein the biphenyl ligand displays a κ²-O,O-bonding motif which accounts for the modest enantioselectivities realized with this system. The less sterically-congested proligands initially form similar monomeric complexes; however, these complexes dimerize diastereoselectively to κ⁴-N,O,O-N-bonding amidate complexes within a few hours in solution. The binding motif of the amidate ligand of the chiral biphenyl tantalum complexes is also dictated by the size of the N-substituent of the ligand. While a bulky proligand results in a discrete tantalum κ²-O,O-bonding amidate complex, less sterically-encumbered proligands produce a mixture of κ²-O,O-bonding and κ³-N,O,O-bonding amidate complexes. Using these tantalum complexes as precatalysts, alkenes undergo hydroaminoalkylation reactions with secondary amines to give branched alkylated secondary amines in isolated yields of up to 92% and enantiomeric excesses reaching 66%, for the first examples of an enantioselective hydroaminoalkylation reaction.

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The synthesis, characterization, and reactivity patterns of three new classes of ureate- supported group 4 compounds are described, constituting the first comprehensive examination of the use of these electron-rich ligands. Four ureates with varying steric and electronic properties are included here: two mono(ureate)s and two tethered bis(ureate)s.Synthesis of dichlorobis(ureato) titanium and zirconium derivatives can be accomplished using several methods, with direct protonolysis between the urea proligand and M(NMe₂)₂Cl₂ precursors giving the highest yield. Solid-state and solution-phase characterization indicates the distal dialkylamino substituent on the ureate donates electron density into the chelate. While use of non-tethered ligands results in zirconium complexes that are fluxional in solution, tethered bis(ureato) ligands support well-defined species. These complexes retain neutral ligands, which are not easily removed. Ureate- supported zirconium dialkyl complexes can also be prepared by protonolysis between a urea and tetraalkyl zirconium compounds. The electron-rich nature of the ureate ligands allows the isolation of coordinatively unsaturated dialkyl complexes.Ureate-supported bis(amido) compounds of titanium and zirconium have been developed as precatalysts for hydroamination. A comprehensive structural comparison between related amidate and ureate complexes reveals that the ureate ligands bind tighter to their metal centers than amidates. As a consequence of this, and the electron-rich nature of the ureate ligands, amidate precatalysts are generally more effective for intramolecular hydroamination of alkenes than ureate precatalysts. In contrast, precatalysts with tethered ureate ligands are more effective than analogous amidates. The most active system identified through catalytic screening exhibits broad substrate scope and functional group tolerance. Most importantly, this is the first group 4 system that is highly effective with both primary and secondary amines.Mechanistic investigations have revealed that catalysis with the tethered bis(ureate) precatalyst does not proceed through an imido-mediated [2+2] cycloaddition-type mechanism. Instead, the key bond forming step is proposed to occur through concerted insertion of the alkene into a Zr–N bond and protonation of the terminal alkene carbon by a coordinated amine ligand. This proposal is supported by stoichiometric and kinetic investigations, which indicate that a proton-source accelerates alkene insertion, and a primary kinetic isotope effect when using an N-deuterated aminoalkene.

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The work reported herein focuses on expanding the reaction scope of known groupfour bis(amidate) and tetrakis(amido) complexes in hydroamination catalysis. Thedevelopment of new titanium and zirconium complexes exhibiting improved reactivity inhydroamination catalysis and unexpected C-C bond formation are disclosed. Theexceptional hydroamination activity of a bis(amidate) titanium bis(amido) precatalysttowards alkynes in the presence of aryl amine co-substrates is elucidated, and the scopeof this reactivity was found to include examples of room temperature intermolecularhydroamination. The application of commercially available tetrakis(dialkylamido)titanium(IV) as a precatalyst for the cyclohydroamination of aminoalkenes to form Nheterocyclic products is a particularly attractive contribution due to the ready availabilityand ease of use associated with this catalyst system.The second section involves efforts to develop more reactive and selectivebis(amidate) bis(amido) hydroamination precatalysts by the rational design andimplementation of new amidate ligands modified for enhanced reactivity and selectivityincluding attempts at enantioselective catalysis. The synthesis and characterization of abis(amidate) titanium bis(amido) complex incorporating electron withdrawingperfluorophenyl groups for enhanced reactivity, along with the assessment of this systemin terms of hydroamination is presented. The synthesis, characterization and evaluation ofchiral amidate ligands for the asymmetric cyclohydroamination of aminoalkenes is alsodescribed.In order to generate more reactive group four hydroamination precatalysts, 2-pyridone and its derivatives were investigated as a new class of amidate N,O chelating proligand. The synthesis and characterization of the first group four bis(2-pyridonate)bis(amido) complexes is presented along with their reactivity towards aminoalkenes.These novel complexes were found to be reactive for both cyclohydroamination andcatalytic intramolecular a-functionalization. The initial findings along with a substratescope analysis, and preliminary mechanistic investigations for this unique and exciting100% atom economic, catalytic C-C bond forming reaction is included.The work described in this dissertation contributes to understanding of group fourmetal catalyzed reactions by illuminating some previously unknown reactivity associatedwith titanium and zirconium as well as by providing further insight into how ligandstructure influences complex reactivity.

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No abstract available.