Hydrogenation and hydrofunctionalisation reactions provide efficient, sustainable methodologies for the manipulation of synthetic handles and the formation of carbon-heteroatom bonds from readily available starting materials. Traditional hydrogenation methods typically require precious or semi-precious transition metal complexes or finely divided powders. Iron-based catalysts offer several advantages over more traditional ‘noble’ metal systems due to the high abundance, long-term availability, low cost and low toxicity of iron. To date, the most powerful iron-catalysed hydrogenation and hydrofunctionalisation reactions have required either highly air-sensitive iron(0) complexes or iron(II) complexes activated with an extremely reactive, pyrophoric organometallic reagent. An operationally simple and environmentally benign formal hydrogenation protocol has been developed using a simple iron(III) salt and NaBH4; an inexpensive, bench stable, stoichiometric reductant. This reaction has been applied to the reduction of terminal alkenes (22 examples, up to 95% yield) and nitro groups (26 examples, up to 95% yield) in ethanol, under ambient conditions (Scheme A1). Two novel series of structurally related alkoxy-tethered N-heterocyclic carbene (NHC) iron(II) complexes have been developed as catalysts for the regioselective hydroboration of alkenes. Significantly, Markovnikov selective alkene hydroboration with pinacolborane (HBpin) has been controllably achieved for the first time using an iron catalyst (11 examples, 35-90% isolated yield) with up to 37:1 branched:linear selectivity (Scheme A2). anti-Markovnikov selective alkene hydroboration was also achieved using catecholborane (HBcat) and modification of the ligand backbone (6 examples, 44-71% yield). In both cases, ligand design has enabled activator-free iron catalysis.

Iron β-diketiminate complexes have great potential as catalysts. Previous work into the coordination chemistry of complexes bearing the β-diketiminate ancillary ligand (Chapter 1) attest to the useful properties of these complexes in catalysis. A handful of literature reports on catalytic systems hint that this could be further extended. Hydrophosphination is a growing field that continues to generate a lot of interest from industry and academia alike. The aims of this project are to investigate hydrophosphination reactions with iron β-diketiminate complexes, to achieve high degrees of regioselectivity from these sterically encumbered complexes and to investigate iron catalysed dehydrocoupling reactions. A combination of synthetic and mechanistic methodologies will be employed in order to achieve definitive insight via NMR spectroscopic analysis, kinetic studies and solid state crystallography. Initial work presented herein (Chapter 2) will focus on the synthesis of iron(II) β-diketiminate complexes. Previously reported literature methods will be explored in order to determine an optimum procedure to use these precatalyst complexes. Initial investigations into hydrophosphination activity of these iron species will then be explored with alkenes. Results of these studies led to serendipitous findings and unexpected results in phosphine dehydrocoupling. The scope of this reactivity was then probed and mechanistic considerations taken into account with findings detailed herein. Radical catalysed reactivity observed will be further discussed. Solvent selectivity will then be discussed with a simple yet highly effective solvent change yielding a complete shift in catalytic activity. Further studies (Chapter 3) highlight the orthogonal reactivity of iron(II) β-diketiminate complexes in hydrophosphination catalysis. Less electronically activated and more atypical substrates have been investigated to determine their activity in hydrophosphination reactions. The synthesis of phosphinoalkenes and phosphinoalkynes for cyclic intramolecular hydrophosphination reactions are detailed along with their catalytic activity. Preliminary mechanistic studies are discussed with radical species again proving crucial to catalytic activity. Selective intermolecular hydrophosphination reactions have been investigated with alkynes. A solvent based switch can be employed wherein the regioselectivity of the reaction is completely altered. Substrate scope, mechanistic considerations and potential future applications are examined in full detail. Dehydrocoupling catalysis can be extended in scope (Chapter 4) from iron catalysed phosphine homocoupling reactions to heterocoupling reactions. Phosphine-silane dehydrocoupling is found to be highly selective for the formation of silaphosphanes, preliminary mechanistic insight and reaction scope is discussed. Analogous amine-silane dehydrocoupling is explored in full. The substrate scope offers insight into reactivity and potential further applications in sequential and tandem catalysis. In depth mechanistic insight is discussed with kinetic analyses. Iron-amido complexes are observed to react in a metathesis mediated cycle via iron hydride species. Finally catalytic alcohol-silane dehydrocoupling is investigated as a synthetic route to protected natural products in organic synthesis. Unsaturated silazanes are potential targets for further dehydrocoupling reactions. Catalytic reactions with pinacolborane led to highly facile desilylation reactions (Chapter 5). Mechanistic considerations hint that the reactions occur via σ-bond metathesis could through iron hydride species. Desilylation activity is then extended to siloxanes and a model developed with potential applications in the depolymerisation of polysilazanes and polysiloxanes.

The iron-catalysed hydrofunctionalisation of alkenes and alkynes has been developed to give a range of functionalised products with control of regio-, chemo- and stereochemistry. Using a bench-stable iron(II) pre-catalyst, the hydrosilylation, hydroboration, hydrogermylation and hydromagnesiation of alkenes and alkynes has been achieved. Iron-catalysed hydrosilylation, hydroboration and hydrogermylation of terminal, 1,1- and 1,2-disubstituted alkyl and aryl alkenes and alkynes was developed, in which the active iron catalyst was generated in situ (Scheme A1). Alkyl and vinyl silanes and pinacol boronic esters were synthesised in good to excellent yield in the presence of a range of functional groups. Catalyst loadings as low as 0.07 mol% were demonstrated, along with catalyst turn-over frequencies of up to 60 000 mol h−1. The iron-catalysed formal hydrocarboxylation of a range of styrene derivatives has been developed for the synthesis of α-aryl carboxylic acids using carbon dioxide and ethylmagnesium bromide as the stoichiometric hydride source (Scheme A2). Detailed mechanistic studies have shown this reaction proceeds by iron-catalysed hydromagnesiation to give an intermediate benzylic organomagnesium reagent. The nature of the active catalyst and reaction mechanism have been proposed.

Catalysis allows for the controlled formation of new bonds, whilst reducing both time and energy expenditure in the process. Catalysis has traditionally been the realm of precious metals, which have been used to carry out a bewildering array of reactions. However, there is an ever-increasing drive for the development of catalytic methodology employing sustainable and environmentally benign catalysts. Two such candidates are organocatalysis, omitting the need for metals where possible, or the use of iron catalysis. Two key areas to the advancement of the of field catalysis are the identification and development of new catalysts as well as an understanding of the mechanisms of established catalytic processes. Novel catalysts can provide many benefits such as enhanced or even novel reactivity, access to new classes of substrates or simply be more readily accessible compared with previously developed catalysts. To this end, the first example of Lewis-base-catalysis using the recently developed cyclopropenimine motif is reported. This was exploited in the trifluoromethylation of aldehydes and ketones using the Rupert-Prakash reagent (Scheme A-1). Scheme A-1 Cyclopropenimine-catalysed trifluoromethylation of aldehydes and ketones Developing an understanding of catalytic methodologies in the terms of their mechanism and active species is also a key area in catalysis. Insight into these can direct the expansion of these systems in terms of both more effective catalysts and tailoring reaction conditions as examples. The iron-catalysed hydromagnesiation of styrene derivatives was studied in detail. This culminated in a proposed mechanism, involving a novel hydride transfer process (Scheme A-2). Studies were carried out using a combination of kinetic analysis and in situ Mössbauer spectroscopy, as well as successfully isolating and studying the reactivity of a catalytically-relevant, formal iron(0)-species.

Iron-catalysed carbonyl reduction, nitro reduction, formal hydroamination, and the radical alkenylation of alkyl halides have been developed. A Simple, easy-to-make, air- and moisture-stable iron(III) amine-bis(phenolate) complex catalysed the hydrosilylation of carbonyl compounds efficiently using triethoxysilane as the reducing agent. The reaction tolerated a wide range of substrates to give the corresponding alcohol products in good to excellent yields after hydrolysis of the hydrosilylated products (Scheme A1). Scheme A1. Iron-Catalysed Hydrosilylation of Carbonyl Compounds. The same catalyst was also an active catalyst for the chemoselective reduction of nitro arenes into corresponding amines using triethoxysilane as reducing agent. The method exhibited excellent chemoselectivity as other reducible functional groups such as halogen, ester, nitrile all kept unchanged during the reaction. This catalytic system was then successfully applied to the formal hydroamination of alkene to give substituted amine in synthetic useful yields under mild condition. The reaction is hypothesised to proceed through a radical intermediate (Scheme A2). Scheme A2. Iron-Catalysed Nitro Reduction and Alkene Formal Hydroamination. Finally, FeCl2-catalysed formal Heck cross-coupling has been developed between alkyl halides and styrenes. The reaction tolerated both electron-rich and electron-neutral substrates to give the products in moderate to excellent yields. Initial studies revealed that the reaction also proceeds through a radical intermediate (Scheme A3). Scheme A3. Iron-Catalysed Formal Heck Cross-Coupling of Functionalised Alkyl Halides.

Thesis advisor: Jeffery A. Byers / This dissertation discusses the development of iron-based catalysts for Suzuki-Miyaura cross-coupling reactions and some of the unique reactivity that was discovered as a direct result of these studies. Chapter one will review the area of iron-catalyzed cross-coupling with an emphasis placed on areas where iron provides complimentary reactivity to other metals. Chapter two will detail the initial discovery of conditions that allow for iron-catalysts to participate in the cross-coupling of aryl boronic esters and alkyl halides. Chapter three will discuss the the development of ligands for iron that allow for more general cross-coupling reactivity to be observed. Finally, chapter four will discuss the unique C-H funtionalization reactivty that has been observed as byproducts in chapters two and three. Digging deeper into this reactivty lead to the discovery of a completely novel three-component coupling reaction mediated by the iron complexes discovered in chapter three. / Thesis (PhD) — Boston College, 2020. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

京都大学 / 新制・論文博士 / 博士(工学) / 乙第13456号 / 論工博第4196号 / 新制||工||1770(附属図書館) / (主査)教授 中村 正治, 教授 大江 浩一, 教授 村田 靖次郎 / 学位規則第4条第2項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DFAM

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Thesis advisor: Jeffery A. Byers / This dissertation will discuss the development of Suzuki-Miyaura cross-coupling reactions catalyzed by iron-based complexes with an emphasis on addressing limitations to their practical application in industrial contexts. Chapter 1 will provide an overview of the development of the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction and key factors which have enabled its prevalent use in various industries, with a comparison to how those factors have limited similar development of iron-catalyzed analogues. Chapter 2 will discuss the initial discovery and subsequent development of a series of iron-based precatalysts for the cross-coupling reaction of unactivated aryl boronic esters and alkyl halides. Chapter 3 will discuss the development and validation of a bench-stable iron(III)-based complex capable of catalyzing the Suzuki-Miyaura cross-coupling reaction between unactivated aryl boronic esters and alkyl halides. To conclude, Chapter 4 will discuss the ability of iron-based complexes to participate in the Suzuki-Miyaura cross-coupling reaction with alkyl tosylate electrophiles and its implications for harnessing the ability of iron catalysis to operate under different mechanistic manifolds. / Thesis (PhD) — Boston College, 2021. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

No description available.