Cross-coupling, which relies on the use of transition metals, is among the most utilized chemical means of establishing carbon-carbon or carbon-heteteroatom bonds between appropriately functionalized sp, sp2, or sp3 centres. However, most cross-coupling reactions rely on the use of palladium to synthesize valuable synthetic targets. This is problematic for the chemical industry as palladium is limited in supply and expensive. Chemists have therefore sought to replace palladium with first-row transition metals (e.g., iron, cobalt and nickel) and recent reports on cobalt and nickel catalyzed cross-coupling reactions indicate that these metals can be used in this capacity. Unfortunately, protocols developed (so far) for these metals are unsuitable for the synthesis of targets with base-sensitive functional groups as they involve strongly basic reaction conditions. Research in this thesis aims to develop both cobalt and nickel pre-formed catalysts that will display high catalytic activity in mildly basic reaction conditions. Current methodologies for cobalt and nickel cross-coupling reactions use either phosphine ligands or NHC ligands of moderate steric bulk (IMes or IPr). Recent advancements in the development of Pd-PEPPSI catalysts have demonstrated that both pre-forming the catalyst and using larger NHC ligands (IPent, IPentCl, or IHept) are required for high catalytic activity in weakly basic conditions. Thus, it was hypothesized that the development of pre-formed cobalt and nickel NHC complexes analogous to their Pd counterparts would improve reactivity in Negishi, Suzuki-Miyaura, and Buchwald-Hartwig amination cross-coupling reactions. Co(IPent)Cl2(Pyr), Co(IPentCl)Cl2(Pyr), and Co2IPr2(OAc)4 were prepared, identified by X-ray crystallography, and evaluated in preliminary Negishi cross-coupling reactions. These complexes were found to be ineffective, but Co2IPr2(OAc)4 was found to be effective for Suzuki-Miyaura cross-coupling. A base screen was performed to enable the use of weak bases, however, the reaction only worked by pre-forming the boronate with n-BuLi, rendering the reaction conditions intolerant of base-sensitive functional groups. [Ni(IPr)]2(µ-Cl)2 , Ni(IPr)Cl(allyl), and Ni(IPent)Cl(allyl) complexes were synthesized and evaluated in Buchwald-Hartwig aminations. Several bases were examined for these reactions but only sodium tert-butoxide was found to be effective. The presence of TEMPO and BHT in these transformations proved deleterious suggesting the involvement of radical intermediates. Finally, stoichiometric reactions were performed to isolate intermediates in the catalytic cycle, supporting the formation of nickel(0).

Chapter one introduces N-heterocyclic carbenes (NHCs) and discusses their use as ligands for rare earth metal complexes, with particular emphasis upon compounds synthesised from 2009 until the present day. Chapter two details the synthesis and characterisation of the homoleptic scandium-NHC complex [Sc(L)3] (L = [OCMe2CH2(1-C{NCHCHNiPr})]). Reactions of [Sc(L)3] with boranes, CO2 and CS2 are described which exploit the relative lability of the Sc–Ccarbene bond and allow formation of [Sc(L)2(OCMe2CH2(1-B'C{NCHCHNiPr}))] (B' = 9-BBN, BPh3, B(C6F5)3, BH3), [Sc(OCMe2CH2(1-O2CC{NCHCHNiPr})3]n, [Sc(L)2(OCMe2CH2 (1-S2CC{NCHCHNiPr})] and [Sc(L)(OCMe2CH2(1-S2CC{NCHCHNiPr})2]2. The chapter also discusses the reactivity of [Sc(L)3] towards substrates containing acidic C–H and N–H bonds and substrates containing polar E–X bonds (where E = C, Si, B, P and X = Cl, I). Chapter three describes the synthesis and characterisation of the NHC substituted scandium benzyl complexes [Sc(Bn)2(L)]2 and [Sc(Bn)(L)2], and the attempted synthesis of NHC substituted scandium aminobenzyl complexes. The reactivity of [Sc(Bn)2(L)]2 with RX substrates (R = alkyl) is discussed in detail; depending on the nature of the alkyl group, these reactions can allow formation of R–Bn , the result of carbon-carbon coupling. The complex [Sc(Bn)(L)Cl]2 has been isolated from these reactions and is structurally characterised. The reactivity of [Sc(Bn)2(L)]2 towards C–H bonds is explored and attempts to prepare NHC substituted scandium hydrides are described. Comparisons of the relative stability and reactivity of [Sc(Bn)2(L)]2 and [Sc(Bn)3(thf)3] are drawn. Chapter four documents the synthesis and characterisation of [Sc(Odtbp)2(L)] (Odtbp = 2,6-di-tert-butylphenoxide), [Sc(Odtbp)(L)2], and the samarium analogue [Sm(Odtbp)(L)2]. The reactivity of these complexes towards various small molecules is described. The chapter also details attempts to prepare the cationic scandium complexes [Sc(L)2][Bort] (Bort = bis[3,3',5,5'-tetra-(tert-butyl)-2,2-diphenolato]borate) and [Sc(L)2][B(Ph)4]. Chapter five provides overall conclusions to the work presented in this thesis. Chapter six contains all experimental and characterising data for the complexes and reactions detailed in this work.

A library of iridium complexes featuring oxazoline and imidazol-2-ylidene ligands were synthesized by reaction of a library of imidazoles with a second library of oxazoline iodides. These complexes were active catalysts for hydrogenations of aryl substituted monoenes. Tri- and 1,1-disubstituted alkenes were hydrogenated quantitatively with ee??s up to 99% at 1 atm hydrogen pressure. Catalyst, substrate, temperature and pressure effects were studied. The iridium complexes were also used for the kinetic study of hydrogenation of 2,3- diphenylbutadiene. This hydrogenation is a stepwise reaction: one double bond was hydrogenated first, then the second one. Both step hydrogenations were zero order in alkene. The consumption of 2,3-diphenylbutadiene was first order in catalyst, and probably first order in hydrogen pressure too. The enantioselectivity for the first step hydrogenation was low. There were match and mismatch catalyst-substrate relationships for the second step hydrogenation, and the enantioselectivities for this step were catalyst controlled. NMR studies indicated that the initiation of the reaction involved both hydrogen and alkene substrate. A competitive experiment was designed to explore the formation of meso-alkane at first step hydrogenation, and the results indicated that the alkane was formed predominantly via an associative mechanism. Four types of conjugate dienes were synthesized and hydrogenated. Different reactivities and selectivities were obtained for each type of dienes. In the best case, a diene was hydrogenated quantitatively with an excellent ent/meso ratio of 20:1.0 and 99% enantioselectivity. The scope, limitation and potential applications of the reactions were discussed. A selection of the dienes was hydrogenated with the Crabtree??s catalyst, for comparison, and the yields, conversions and diastereoselectivities were inferior to those from iridium-oxazoline-imidazol-2-ylidene catalysts.

As part of a worldwide effort to develop efficient catalysts for use in organic chemistry and in the synthesis of highly valuable molecules, work performed during the course of my stay in St Andrews has focused on the design and synthesis of new group 11 metal complexes for their applications in catalysis. The aim of this work was to develop new, active and stable, easy to synthesise group 11 complexes and investigate their catalytic activity as well as to try to understand their mode of action. Two different types of complexes were explored in order to develop more active catalysts: the neutral N-Heterocyclic carbene metal complexes and the cationic derivatives. More than 20 new catalysts were developed and their reactivity studied in different catalytic reactions. New hydroxide and tert-butoxide copper(I) or silver(I) complexes were developed and compared to the common NHC metal systems. Overall, the neutral NHC-metal catalysts showed to be highly active in a broad range of applications: in the methylation of amines using CO₂ as a C1 source, in a multicomponent reaction (A³ coupling) and in dual catalysis (hydrophenoxylation). Additionally, mechanistic studies were undertaken to obtain a greater understanding of these transformations and to possibly lead to the design of new generations of catalyst. Regarding the cationic NHC metal complexes, a straightforward methodology was developed leading to a library of highly stable catalysts. Bis-NHC, mixed NHC/ phosphine as well as NHC/pyridine species were efficiently synthesised using thermal or microwave heating, in high purity and yields. In addition, the effect of the presence of two different or identical ligands on catalytic reactivity was investigated in the 3+2 cycloaddition and in the alkynylation of ketones. Insight into the catalytic cycle was obtained via mechanistic studies. These showcased the release of one ligand during the catalytic cycle and the crucial role of this ligand displacement in generating the catalytically relevant active species. The results highlight the importance of understanding the reactivity of catalyst in order to develop new and improved ones.

No description available.

The recent development of materials with autonomous repair capabilities has opened an exciting new field of polymer science expected to impact nearly every facet of modern society. Similar to natural systems, these "self-healing" materials sense when their structural integrity has been compromised (e.g., due to wear or damage) and respond with a viable repair mechanism. Despite the extraordinary number of successes and advances in this area, a means to ascertain instantaneous knowledge of a material's structural integrity, and more importantly, when it has been compromised, remains a considerable challenge in current systems and materials. To address this challenge, we report recent efforts toward the development of an electronically conductive material that is structurally dynamic and responds to various types of external stimuli. In particular, we have developed new synthetic methodology to prepare a variety of organometallic polymers containing a novel benzobisimidazolylidene or bis(benzoimidazolylidene) ligand, which is comprised of two linearly opposed N-heterocyclic carbenes (NHCs) annulated to a common linker, and various types of transition metals in the polymer's main-chain. Using this approach, polymers with molecular weights up to 10⁶ Da were prepared and cast into robust thin films. Using four-point probe technique, the inherent conductivities of these materials were found to be on the order of 10⁻³ S/cm. Secondly, the dynamics of these polymers were probed in solution using gel permeation chromatography. At specific cross-linker loadings, thermally-responsive gels were obtained. Collectively, these experiments suggested that the essential features for a thermally-responsive, structurally dynamic, conjugated organometallic polymer were developed. Efforts toward probing their ability to display self-healing characteristics in the solid-state are described. The inherent conductivity of the polymers permitted the healing behavior of thin films to be observed by scanning electron microscopy in the absence of a dopant. Long range goals of implementing and utilizing these materials in electronic circuits and other advanced devices are also described. An additional approach towards a dynamic material utilized functional imidazolium-based ionic liquids. A series of functional ionic liquids were produced by appending N-substituents containing pendant halides, alkynes, azides, furans and maleimides. These functional groups allowed for polymerization and crosslinking. The physical properties of the imidazolium monomers, as well as the resulting polymers, could be tuned by altering the anion. When a trifunctional monomer is used in conjunction with the polymerization of difunctional ionic liquids an insoluble crosslinked material forms. This behavior, combined with NHCs ability to bind transition metals as ligands and catalyze various organic transformations, provides potential for this system to be used as a method for catalyst recovery and ultimately catalyst recycling. / text

Chemistry / The efforts described in this thesis were bifurcated along two distinct projects, but generally were directed toward the development of new materials to solve outstanding issues in contemporary electrochemical applications. The first project involved the synthesis and application of redox-switchable olefin metathesis catalysts. N-heterocyclic carbenes (NHCs) bearing ferrocene and other redox-active groups were designed, synthesized, and incorporated into model iridium complexes to evaluate their intrinsic electrochemical and steric parameters. Using these complexes, the ability to switch the electron donating ability of the ligands via redox processes was quantified using a variety of electrochemical and spectroscopic techniques. The donicity was either enhanced or attenutated upon reduction or oxidation of the redox-active group, respectively. The magnitude of the change in donicity upon reduction or oxidation did not vary significantly as a function of the proximity of the redox-active group from the metal center. Thus, other factors, including synthetic considerations, sterics, and redox potential requirements, were determined to guide ligand design. Regardless, redox-active NHCs were adapted into ruthenium-based olefin metathesis catalysts and used to gain control control over various ring-opening metathesis polymerizations and ring-closing metathesis reactions. The second project was focused on the development of new basic polymers for acid/base crosslinked proton exchange membranes intended for applications in direct methanol fuel cells. Polymers containing pendant pyridinyl and pyrimidinyl groups were obtained via the post polymerization functionalization of UDEL® poly(sulfone) and then blended with sulfonated poly(ether ether ketone) (SPEEK). Fuel cells containing these blends were found to exhibit reduced methanol crossover, higher open circuit voltages, and higher maximum power densities compared to plain SPEEK. The differences in fuel cell performance were attributed to the basicity and sterics of the pendant N-heterocycles. / text

Thesis advisor: Amir H. Hoveyda / Chapter 1. A Review of Catalytic Enantioselective Allylic Substitution (EAS) with Chiral Sulfonate Containing N-heterocyclic Carbenes (NHC). A comprehensive review of enantioselective allylic substitution reactions, which are promoted by a chiral N-heterocyclic carbene metal complex that features a unique sulfonate motif, is provided in this chapter. Reactions are classified into two categories. One class of transformations is catalyzed by a series of easily modifiable sulfonate bearing NHC-Cu complexes, with which a range of nucleophilic organometallic reagents (i.e., organozinc-, aluminum-, magnesium- and boron-based) that carry different carbon-based units are readily utilized in efficient and highly selective C-C bond forming processes. Another set of reactions exclude the use of a copper salt; catalytic amount of a sulfonate containing imidazolinium salt is capable of promoting additions of alkyl Grignard, zinc and aluminum species to easily available allylic electrophiles in a site- and enantioselective fashion. The mechanistic scenarios of both catalytic systems that account for the observed experimental data are discussed in detail. Chapter 2. Cu-Catalyzed Enantioselective Allylic Substitutions with Aryl- and Heteroarylaluminum Reagents. In this chapter, the first examples of EAS reactions of aryl- and heteroaryl-substituted dialkylaluminum reagents to a wide range of trisubstituted allylic phosphates are demonstrated through a facile and selective catalysis rendered possible by an in situ generated sulfonate containing NHC-Cu complex, delivering enantiomerically enriched olefin products that bear an all carbon quaternary stereogenic center. The requisite organometallic species are easily prepared from either the corresponding aryl- and heteroaryl halides, or through efficient and site selective deprotonation at the C-2 position of furan and thiophene; such aluminum entities are readily used in situ without the requirement of purification. Application to small molecule natural product synthesis is also carried out to illustrate the utility of the present protocol. Chapter 3. Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylaluminum Reagents. This chapter focuses on our research towards construction of enantioenriched tertiary and quaternary stereogenic centers that are substituted with two further functionalizable alkenes. The first combination of the study involves the addition of stereochemically well-defined trisubstituted alkenylaluminum reagents to disubstituted allylic phosphates; the transformation commences with a silyl-directed stereoselective hydroalumination and finishes with an enantioselective Cu-catalyzed EAS promoted by a sulfonate bearing NHC. Such reactions deliver molecules that feature silicon containing trisubstituted olefin adjacent to the tertiary stereogenic center; subsequent conversion of the versatile silicon group to a proton reveals the first set of examples that incorporate pure Z alkene in Cu-catalyzed EAS. The stereoselective and concise synthesis of naturally occurring small molecule nyasol demonstrates the utility of the above method. On a different front, Ni-catalyzed site-selective hydroalumination of terminal alkynes has opened new possibility of introducing 1,1-disubstituted olefins in Cu-catalyzed EAS in the formation of tertiary stereogenic center containing enantioenriched organic building blocks. Such catalytic hydrometallation procedure also allows efficient access to alkenylaluminums that are derived from the conventionally problematic aromatic alkynes. The importance of efficient and selective synthesis of terminal aryl-substituted alkenylaluminum species is showcased in NHC-Cu-catalyzed EAS reactions that construct all-carbon quaternary stereogenic centers; a three-step convergent synthesis of natural product bakuchiol in enantiomerically enriched form highlights the potential of the current protocol in chemical synthesis. Chapter 4 Cu-Catalyzed Enantioselective Allylic Substitutions with Alkenylboronic Acid Pinacol Ester Reagents and Applications in Natural Product Synthesis. Within this chapter, we disclose the efficient utilization of alkenylboron reagents in Cu-catalyzed EAS reactions, which lead to highly site and enantioselective formations of molecules that contain both tertiary and quaternary carbon stereogenic centers. Unlike their aluminum-based counterparts, the use of boron-based reagents allows effective delivery of sensitive organic function groups, such as a carbonyl, which would be incompatible in the hydrometallation process with dibal-H. Our efforts accumulate to the first report of incorporation of all carbon quaternary centers that are substituted with unsaturated ester and aldehyde units in the EAS products; such a method facilitates the concise diastereo- and enantioselective synthesis of Pummerer's ketone and it's trans isomer. Further development of the above protocol towards the construction of tertiary stereogenic centers requires the design of new chiral sulfonate-containing imidazolinium salts as the ligand precursors and has lead to the employment of a broader range of alkenylboron species, which feature readily functionalizable motifs. Subsequent demonstrations in enantioselective synthesis of a variety of small molecule natural products showcase the utility. / Thesis (PhD) — Boston College, 2013. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

Thesis advisor: Marc L. Snapper / Chapter 1. A Practical Synthesis of 3-Acyl Cyclobutanones by [2 + 2] Annulation. Mechanism and Utility of the Zn(II)-Catalyzed Condensation of alpha-Chloroenamines with Electron-Deficient Alkenes. We have developed a catalytic method for the synthesis of highly functionalized 3-acyl cyclobutanones which are useful building blocks for a variety of natural products. Methods for cyclobutanone synthesis have traditionally been limited to Lewis-acid promoted rearrangement of oxaspiropentanes or cyclizations of ketene and syntheses involving keteneiminium salts have required stoichiometric quantities of a Lewis acid. Furthermore, the mechanism for these types of cyclizations remains unknown. This portion of my research focused on an efficient, catalytic method for the synthesis of 3- acyl cyclobutanones and providing insight into the mechanism for cycloaddition. Chapter 2. Enantioselective Synthesis of Boron-Substituted Quaternary Carbons by NHC-Cu-Catalyzed Boronate Conjugate Additions to Unsaturated Carboxylic Esters, Ketones, or Thioesters. We have developed an enantioselective NHC-Cu-catalyzed conjugate addition of boronate esters to acyclic, trisubstituted alpha, beta-unsaturated carbonyl compounds. Enantioselective conjugate addition of a boronic acid pinacol ester through the use of bis(pinacolato)diboron [B2(pin)2,] to alpha, beta-unsaturated aliphatic and aryl esters promoted by 5 mol % of an NHC-Cu catalyst afforded tertiary beta-boryl carbonyls in high efficiency and enantioselectivity. Trisubstituted alpha, beta-unsaturated esters and thioesters were found to be reactive substrates in the presence of a stoichiometric quantity of methanol. Chapter 3. Metal-Free Catalytic C-Si Bond Formation in an Aqueous Medium and C-B Bond Formation in a Protic Medium. Enantioselective NHC-Catalyzed Silyl and Boryl Conjugate Additions to Cyclic and Acyclic alpha, beta-Unsaturated carbonyls. We have developed a method for enantioselective metal-free silyl conjugate additions through the use of dimethylphenylsilyl) boronic acid pinacol ester [PhMe2SiB(pin)] catalyzed by chiral N-heterocyclic carbenes (NHCs) in basic aqueous thf. Optimization of metal-free conditions demonstrated that the presence of water was required for high efficiency. alpha, beta-Unsaturated cyclic ketones and lactones were examined as substrates, and acyclic ketones, esters and aldehydes were also competent substrates for silyl conjugate addition. beta-Silyl carbonyls were isolated in up to >98% yield and >98:2 er. Chapter 4. Elucidation of Mechanism for Enantioselective NHC-Catalyzed Silyl Conjugate Addition. We propose a catalytic cycle for NHC-catalyzed enantioselective silyl conjugate addition. Mechanistic studies of NHC-catalyzed enantioselective silyl conjugate additions are presented. Optimization of conditions for an inefficient alpha, beta-unsaturated electron-deficient ketone provided insight into the roles for dbu and water. Kinetic data indicate that conjugate addition is first order in PhMe2SiB(pin) and carbene, and DFT calculations support the formation of an NHC-silyl anion as a reactive intermediate in the catalytic cycle. / Thesis (PhD) — Boston College, 2012. / Discipline: Chemistry.

Thesis advisor: Amir H. Hoveyda / Chapter 1 Catalytic Enantioselective Addition of Organoaluminum Reagents Catalytic methods involving the enantioselective addition of both commercially available as well as in situ generated organoaluminum reagents are reviewed. An overview of additions to aldehydes, ketones, and imines is provided as well as the difficulties and limitations of such transformations. Furthermore, additions to unsaturation adjacent to a leaving group to form a new stereogenic center are examined. Finally, conjugate addition reactions wherein an organoaluminum reagent is added to an olefin adjacent to a carbonyl or nitro group are discussed. Chapter 2 Synthesis of Quaternary Carbon Stereogenic Centers through Enantioselective Cu-Catalyzed Allylic Substitution with Alkenylaluminum Reagents A method for the formation of 1,4-diene containing quaternary stereogenic centers through catalytic enantioselective allylic substitution is disclosed. The addition of alkyl- and aryl-substituted alkenylaluminum reagents to trisubstituted allylic phosphates is promoted by 0.5–2.5 mol % of a sulfonate-containing bidentate N-heterocyclic carbene–copper complex. Products containing a quaternary stereogenic center as well as a newly formed terminal olefin are obtained in up to 97% yield and 99:1 er with high site selectivity (>98:2 SN2’:SN2). The requisite nucleophiles are generated in situ through hydroalumination of terminal alkynes. The utility of the method is demonstrated through a concise synthesis of natural product bakuchiol. Chapter 3 A Multicomponent Ni-, Zr-, Cu-Catalyzed Strategy for Enantioselective Synthesis of Alkenyl-Substituted Quaternary Carbons Despite the widespread use of conjugate addition in organic synthesis, few reports pertain to the addition of nucleophiles to acyclic systems and none in which the nucleophile is an alkene. Herein, we report the first examples of enantioselective conjugate addition of alkenylmetal reagents to trisubstituted enones to form all-carbon quaternary stereogenic centers. Alkenylaluminum nucleophiles are prepared through a site-selective Ni-catalyzed hydroalumination of terminal alkynes and the requisite E-trisubsituted enones are the products of a regioselective Zr-catalyzed carboalumination/acylation of a terminal alkyne. Products are obtained in up to 97% yield and 99:1 er. A model for enantioselectivity, supported by DFT calculations, is proposed. Chapter 4 Formation of Tertiary Centers through Catalytic Enantioselective Conjugate Addition of Alkenylaluminum Reagents to Acyclic Enones We have developed an enantioselective NHC–Cu catalyzed synthesis of tertiary centers in acyclic systems using in situ generated alkenylaluminum reagents, as current methods typically rely on Rh-catalysis at high temperatures with alkenyl boronic acids in protic solvents. Moreover, most examples include chalcone-derived substrates, which, while more reactive, often preclude further functionalization. With the current method, we are able to couple a variety of alkenyl nucleophiles with α,β-unsaturated ketones. E- or Z-silylalkenylaluminum reagents, derived from hydroalumination of silyl-protected alkynes, lead to products in good yields and high enantioselectivities. Additionally, both the α- and β-alkenylaluminum reagents participate in the reaction. Chapter 5 Development of N-Heterocyclic Carbene–Cu Catalyzed Allylic Substitution of Diboryl Methane to Morita-Baylis-Hillman Derived Allylic Phosphates We have developed a method for the coupling of a geminyl diboron reagent with Morita-Baylis-Hillman derived trisubstituted ester-containing allylic phosphates. With 10 mol % of an in situ generated NHC–Cu complex and 1.5 equivalents of the boron reagent, we are able to form the desired product in high regio- and enantioselectivity with a 2,5-ditert-butyl containing carbene. Simple aryl substituents as well as those containing a halogen or an electron-withdrawing group furnish the desired products in up to 85% yield and 98:2 er. Alkyl-containing substrates are also competent reaction partners, although longer chain aliphatics results in slightly diminished enantioselectivity. We are pursuing the application of this method to the synthesis of α-methylene lactones which can be further functionalized to natural products like tubulin polymerization inhibitor (–)-steganone and glaucoma medication (+)-pilocarpine. / Thesis (PhD) — Boston College, 2016. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.