| 1. |
- Bielawski, Marcin, 1981-
(författare)
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Diaryliodonium Salts : Development of Synthetic Methodologies and α-Arylation of Enolates
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes novel reaction protocols for the synthesis of diaryliodonium salts and also provides an insight to the mechanism of α-arylation of carbonyl compounds with diaryliodonium salts. The first chapter gives a general introduction to the field of hypervalent iodine chemistry, mainly focusing on recent developments and applications of diaryliodonium salts. Chapter two describes the synthesis of electron-rich to electron-poor diaryliodonium triflates, in moderate to excellent yields from a range of arenes and iodoarenes. In chapter three, it is described that molecular iodine can be used together with arenes in a direct one-pot, three-step synthesis of symmetric diaryliodonium triflates. A large scale synthesis of bis(4-tert-butylphenyl)iodonium triflate is also described, controlled and verified by an external research group, further demonstrating the reliability of this methodology. The fourth chapter describes the development of a sequential one-pot synthesis of diaryliodonium salts from aryl iodides and boronic acids, furnishing symmetric and unsymmetric, electron-rich to electron-poor diaryliodonium tetrafluoroborates in moderate to excellent yields. This method was developed to overcome the regiochemical limitations imposed by the reaction mechanism in the protocols described in the preceding chapters. Chapter five describes a one-pot synthesis of heteroaromatic iodonium salts under similar conditions described in chapter two. The final chapter describes the reaction of enolates with chiral diaryliodonium salts or together with a phase transfer catalyst yielding racemic products. DFT calculations were performed, which revealed a low lying energy transition state (TS) between intermediates, which is believed to be responsible for the lack of selectivity observed in the experimental work. It is also proposed that a [2,3] rearrangement is preferred over a [1,2] rearrangement in the α-arylation of carbonyl compounds. The synthetic methodology described in this thesis is the most generally applicable, efficient and high-yielding to date for the synthesis of diaryliodonium salts, making these reagents readily available for various applications in synthesis.
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| 2. |
- Di Tommaso, Ester Maria, 1991-
(författare)
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Synthetic and Mechanistic Studies with Iodine(III) Reagents
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes the development of metal-free transformations and mechanistic studies on the reactivity of two classes of hypervalent iodine reagents: diaryliodonium salts and vinylbenziodoxolones (VBX). Recently, they have been recognized as valuable synthetic reagents with broad applicability in organic synthesis. Moreover, hypervalent iodine reagents are non-toxic compounds and sustainable alternatives to heavy metals. In Chapter 1, an overview of hypervalent iodine(III) compounds is provided, with emphasis on the reagents that have been used in the thesis. First, the synthesis and general reactivity of diaryliodonium salts is described. Vinylbenziodoxolones are presented as a novel class of iodine(III) compounds that are powerful electrophilic vinylating reagents. Finally, a brief description of density functional theory and computational methods used in this thesis are outlined. The synthesis and applications of azobenzene-derived diaryliodonium salts is the topic of Chapter 2. The novel iodonium reagents were employed in chemoselective arylation reactions with a wide range of C, N, O and S-nucleophiles under mild and metal-free conditions. In Chapter 3, a mild and transition metal-free vinylation of thiols and mercapto heterocycles using vinylbenziodoxolones reagents is presented. The method allows the synthesis of a wide variety of S-vinylated products with complete chemo-, regio- and stereoselectivity. In Chapter 4, the first mechanistic investigation of VBX vinylations is presented. By exploiting the use of NMR analysis, deuterium labelling and DFT calculations, the observed regio- and stereochemical outcome of the vinylations of sulfur and phosphorous nucleophiles with VBX reagents has been rationalized. A transition metal-free, photocatalyzed C-vinylation method using VBX reagents is described in Chapter 5. The reactions proceed under mild conditions and the method tolerates a series of functional groups that lead to straightforward access to corresponding alkenes in good to high yields with high stereoselectivity.
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| 3. |
- Huang, Xiao, 1987-
(författare)
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Conducting Redox Polymers for Electrode Materials : Synthetic Strategies and Electrochemical Properties
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic electrode materials represent an intriguing alternative to their inorganic counterparts due to their sustainable and environmental-friendly properties. Their plastic character allows for the realization of light-weight, versatile and disposable devices for energy storage. Conducting redox polymers (CRPs) are one type of the organic electrode materials involved, which consist of a π-conjugated polymer backbone and covalently attached redox units, the so-called pendant. The polymer backbone can provide conductivity while it is oxidized or reduced (i. e., p- or n-doped) and the concurrent redox chemistry of the pendant provides charge capacity. The combination of these two components enables CRPs to provide both high charge capacity and high power capability. This dyad polymeric framework provides a solution to the two main problems associated with organic electrode materials based on small molecules: the dissolution of the active material in the electrolyte, and the sluggish charge transport within the material. This thesis introduces a general synthetic strategy to obtain the monomeric CRPs building blocks, followed by electrochemical polymerization to afford the active CRPs material. The choice of pendant and of polymer backbone depends on the potential match between these two components, i.e. the redox reaction of the pendant and the doping of backbone occurring within the same potential region. In the thesis, terephthalate and polythiophene were selected as the pendant and polymer backbone respectively, to get access to low potential CRPs. It was found that the presence of a non-conjugated linker between polymer backbone and pendant is essential for the polymerizability of the monomers as well as for the preservation of individual redox activities. The resulting CRPs exhibited fast charge transport within the polymer film and low activation barriers for charge propagation. These low potential CRPs were designed as the anode materials for energy storage applications. The combination of redox active pendant as charge carrier and a conductive polymer backbone reveals new insights into the requirements of organic matter based electrical energy storage materials.
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| 4. |
- Jalalian, Nazli, 1982-
(författare)
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Development and Applications of Hypervalent Iodine Compounds : Powerful Arylation and Oxidation Reagents
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis describes the efficient synthesis of several hypervalent iodine(III) compounds. Electron-rich diaryliodonium salts have been synthesized in a one-pot procedure, employing mCPBA as the oxidant. Both symmetric and unsymmetric diaryliodonium tosylates can be isolated in high yields. An in situ anion exchange also enables the synthesis of previously unobtainable diaryliodonium triflates.A large-scale protocol for the synthesis of a derivative of Koser’s reagent, that is an isolable intermediate in the diaryliodonium tosylate synthesis, is furthermore described. The large-scale synthesis is performed in neat TFE, which can be recovered and recycled. This is very desirable from an environmental point of view.One of the few described syntheses of enantiopure diaryliodonium salts is discussed. Three different enantiopure diaryliodonium salts bearing electron-rich substituents are synthesized in moderate to high yields. The synthesis of these three salts shows the challenge in the preparation of electron-rich substituted unsymmetric salts.The second part of the thesis describes the application of both symmetric and unsymmetric diaryliodonium salts in organic synthesis. A metal-free efficient and fast method for the synthesis of diaryl ethers from diaryliodonium salts has been developed. The substrate scope is wide as both the phenol and the diaryliodonium salt can be varied. Products such as halogenated ethers, ortho-substituted ethers and bulky ethers, that are difficult to obtain with metal-catalyzed procedures, are readily prepared. The mild protocol allows arylation of racemization-prone a-amino acid derivatives without loss of enantiomeric excess.A chemoselectivity investigation was conducted, in which unsymmetric diaryliodonium salts were employed in the arylation of three different nucleophiles in order to understand the different factors that influence which aryl moiety that is transferred to the nucleophile.
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| 5. |
- Kervefors, Gabriella, 1988-
(författare)
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Transition Metal-Free O-, N- and S-Arylations with Diaryliodonium Salts
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the development of metal-free arylation procedures using diaryliodonium salts, a non-toxic and versatile electrophilic arylating reagent, with applications to synthesize biologically relevant targets.The first part describes a transition metal-free formal synthesis of phenoxazine with an O-functionalization of a certain phenol as a key step. Using a designed, unsymmetrical diaryliodonium salt, O-arylation provided an ortho-disubstituted diaryl ether which was cyclized to acetyl phenoxazine. An unusually stable iodine(III) intermediate was observed by NMR which could be converted to the product upon heating or applying a longer reaction time. This finding has an impact on the general understanding of ligand coupling mechanism which diaryliodonium salts follow.The second and third part describes arylation of nitrogen nucleophiles. A general N-arylation of aliphatic amines under mild conditions was developed. The reaction has a broad substrate scope with a great variety in acyclic and cyclic primary and secondary amines, as well as diaryliodonium salts. The developed protocol is applicable for aryl transfer of both electron-poor and electron-rich aryl groups, the latter delivering products that had previously not been synthesized in a transition metal-free manner.The successful N-arylation methodology was subsequently broadened to allow N-arylation of amino acid derivatives, resulting in a more general method to access biologically interesting compounds in a metal-free fashion which has never been reported in combination with diaryliodonium salts. The reaction could transfer a variety of aryl groups without compromising the stereocenter of the amino acid ester.The last part describes the S-arylation of thioamides, resulting in the formation of thioimidates, a relatively unstudied class of compounds where the majority of the formed products are novel. Both electron-rich and electron-poor aryl groups could be transferred with high chemoselectivity and a large ortho-effect was observed. Furthermore, when examining this arylation procedure with cyclic thioamides, a different trend was observed and N-arylated thioamides were isolated.
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| 6. |
- Linde, Erika, 1992-
(författare)
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New Reactivity in Diaryliodonium Salt Chemistry
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Diaryliodonium salts (Ar2IX) have emerged as versatile multi-purpose reagents with desirable properties such as easy accessibility, low toxicity and applicability under mild and metal-free reaction conditions. Despite displaying broad utility in arylations of both carbon and heteroatom nucleophiles, the overall sustainability of these protocols is compromised by featuring poor atom economy due to the formation of stochiometric iodoarene byproducts. In this thesis, this imperative drawback was addressed by development of a novel class of diaryliodonium salts with unprecedented reactivity that prevents the formation of iodoarene waste by incorporating both aryl groups as well as the iodine-component into the final products. The first project concerns the development and design of ortho-fluorinated iodonium salts, where updated synthetic protocols were established to attain extensive salt scopes with diverse functionalities. The unique design of these reagents unveiled a cascade reaction whereby heteroatom-diarylated products were formed through concomitant nucleophilic aromatic substitution and intramolecular aryl transfer. The second project focuses on the applications of the ortho-fluorinated salts in diarylations of aliphatic amines, anilines, ammonia and water to attain industrially important diaryl- and triaryl amines as well as diaryl ethers (>100 examples). This atom-efficient methodology allows for transfer of two different aryl groups in a single step under mild and metal-free conditions, giving structurally diverse multi-arene products that would otherwise require expensive and time-consuming multi-step synthesis. The third project explores the potent combination of the diarylation strategy with the structural diversification of secondary aliphatic amines in the preparation of densely functionalized diarylamines. Cyclic amines constitute essential cornerstones in drug discovery and incorporation of such valuable moieties in Ar2IX reagents is of considerable interest. By further exploiting the SNAr reactivity of the ortho-fluorinated diaryliodonium salts, a previously inaccessible class of amino-functionalized Ar2IX were prepared by reactions with cyclic amines. These N-functionalized reagents were utilized in a one-pot sequential arylation/ring opening pathway, where intramolecular arylation afforded diarylammonium salts in situ, which upon reaction with external nucleophiles underwent deconstructive C-N functionalizations. The methodology enables atom- and step-economical access to value-added diarylamines with versatile functionalities at both the C- and N- terminal. The final project emphasizes the applicability of the diarylated products as versatile building blocks in various downstream functionalizations. The retention of the iodine-component enables diversification by a range of transition metal-catalysed cross-couplings, delivering products with increased structural complexity. The significance of the diarylation methodology was further demonstrated in the three-step synthesis of the drug molecule NMP-7. Two protocols were developed for transformation of the ortho-iododiaryl ethers into oxygen-bridged cyclic diaryliodonium salts and acyclic aryloxy salts. The synthetic utility of these unexplored Ar2IX reagents was demonstrated in metal-free, chemoselective functionalizations of common nucleophiles.
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| 7. |
- Lindstedt, Erik, 1987-
(författare)
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Metal-Free O- and C-Arylation with Diaryliodonium Salts
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the development of metal-free applications using diaryliodonium salts. The first project describes an arylation protocol of allylic and benzylic alcohols in aqueous media. The method proceeds under mild conditions and the ether products were obtained in moderate to good yields. The methodology was also expanded to include arylation of phenols, giving diaryl ethers in good to excellent yields. In the second project, an arylation method that included a wider range of aliphatic alcohols was developed. The scope of accessible alkyl aryl ethers was studied and included a comparative study of phenylation and nitrophenylation of various alcohols. Finally, a formal metal-free synthesis of butoxycain was performed, illustrating the applicability of the developed method.The third project focused on the limitations and side reactions occurring in Chapter 2 and 3. First, an approach to access symmetric diaryl ethers via arylation of hydroxide was presented. This reaction gave rise to a number of side products, which we hypothesized to originate from aryne-type intermediates. A mechanism for the formation of these side products was suggested, supported by trapping and deuterium labeling experiments.Oxidation of the alcohol to the corresponding ketone was also observed and the mechanism of this interesting side reaction was investigated. The latter was suggested to proceed via an intramolecular oxidation without the involvement of radicals or arynes.The fourth project covers a method to synthesize highly sterically congested alkyl aryl ethers via arylation of tertiary alcohols using diaryliodonium salts. The method displayed a broad scope of tertiary alcohols and was also suitable for fluorinated alcohols.The final project detailed in this thesis deals with C-arylation with diaryliodonium salts, showcasing nitroalkanes as well as a nitro ester as suitable nucleophiles for metal-free arylation.
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| 8. |
- Malmgren, Joel, 1985-
(författare)
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Iodonium Salts : Preparation, Chemoselectivity and Metal-Catalyzed Applications
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns the preparation and use of diaryliodonium salts. In Project I various unsymmetrical diaryliodonium salts were reacted with three different nucleophiles in order to study the chemoselectivity of the reactions of the salts. The main focus of this project was to gain a deeper understanding of the underlying factors that affect the chemoselectivity in transition metal-free arylation reactions. They were found to be very nucleophile-dependent. Some nucleophiles were very sensitive to electronic effects, whereas others were sensitive to steric factors. Ultimately, some arenes are never transferred. A very interesting scrambling reaction was also observed under the reaction conditions, where unsymmetrical diaryliodonium salts form symmetrical salts in situ.Project II details the preparation of N-heteroaryliodonium salts via a one-pot procedure. The salts were designed so that the N-heteroaryl moiety was selectively transferred in applications both with and without transition metals. The chemoselectivity was demonstrated by selective transfer of the pyridyl group onto two different nucleophiles.The third project in the thesis discusses the synthesis of alkynyl(aryl)iodonium salts and alkynylbenziodoxolones from arylsilanes. This protocol could potentially be a very useful complement to the existing procedures, in which boronic acids are used.The last part of the thesis (Project IV) describes a C-2 selective arylation of indoles where diaryliodonium salts were used in combination with hetero-geneous palladium catalysis. This transformation was performed in water at ambient temperature to 50 °C, and tolerated variations of both the indole and the diaryliodonium salt. Importantly, several N-H indoles could be arylated. The MCF-supported Pd-catalyst showed very little leaching and it was demonstrated that the main part of the reaction occurred via heterogeneous catalysis.
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| 9. |
- Olofsson, Berit, 1972-
(författare)
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A Regio- and Stereodivergent Route to All Isomers of vic-Amino Alcohols
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The first part of this thesis describes a synthetic strategythat provides all eight possible isomers of a given vic-aminoalcohol starting from vinylepoxides. The value of a generalroute is evident, as several isomers are needed ininvestigations of structure-activity relationships forpharmacologically active derivatives, and for optimizing theperformance of chiral ligands containing the amino alcoholmoiety.Vinylepoxides, obtained in high enantiomeric excess, werering-opened both with inversion and retention ofstereochemistry, delivering two diastereomeric amino alcoholswith high regio- and stereoselectivity. Via ring-closure toaziridines and subsequent regioselective ring-opening withsuitable oxygen nucleophiles, the two remaining amino alcoholswere selectively achieved.Within this study, two efficient protocols for theregioselective and stereospecific aminolysis of vinylepoxideshave been presented. Comparedto previous methods, theseprocedures use milder reaction conditions, shorter reactiontimes, generally give higher yields and are applicable to alarger set of substrates. Furthermore, the ring-closure ofvic-amino alcohols to the corresponding N-H vinylaziridines hasbeen investigated. Three routes have been found useful, whichone is preferred depends on substrate and scale.In the second part of the thesis, the synthetic strategy isapplied on the synthesis of Sphingosine and its regio- andstereoisomers. Moreover, a rapid way of determining relativeconfiguration of vic-amino alcohols is described, which shouldbe of substantial use when amino alcohols are formed bydiastereoselective reactions.amino alcohols, vinylepoxides, vinylaziridines, oxazolines,oxazolidinones, ring-opening, regioselective,diastereoselective, sphingosine, configuration, NMRspectroscopy.
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| 10. |
- Reitti, Marcus, 1986-
(författare)
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Diaryliodonium Salts : Synthesis, Applications and Computational Investigations
- 2019
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organic chemists have the ability to create complex organic molecules by connecting molecular building blocks in different ways. To name a few, these molecules are used as medicines, pesticides or in our household electronics, and are therefore crucial to life as we know it. While many excellent methods for the connection of these fragments are known, serious issues regarding efficiency and sustainability remain. Our research concerns the use of diaryliodonium salts as a way of improving on these issues. Diaryliodonium salts are hypervalent iodine reagents used to transfer aryl groups to suitable nucleophiles. This thesis concerns the synthesis of these reagents and their use in the formation of carbon-nitrogen and carbon-oxygen bonds.The first project investigates the possibility to synthesize unsymmetrical diaryliodonium salts starting from elemental iodine and arenes, as such a method could be more cost efficient and sustainable compared to existing methods starting from iodoarenes. It was found that highly sterically congested diaryliodonium salts could be synthesized in high yields.Next, we applied diaryliodonium salts in the arylation of nitrite to form aromatic nitro compounds. The methodology offered a broad scope with good to excellent yields. Furthermore, we presented the in situ functionalization of diaryliodonium salts that had been formed from iodoarenes and arenes. This conceptually novel approach could be a step towards a catalytic reaction using diaryliodonium salts.In the third project we investigated the mechanisms of O-arylations with diaryliodonium salts to provide a deeper understanding of the reaction pathways involved in product and byproduct formation. Reactions between electron-rich diaryliodonium salts, hydroxides or secondary alcohols were studied. When using hydroxide as the nucleophile, the side products could be suppressed by the addition of aryne traps, suggesting such an intermediate in the reaction. A novel mechanism for the formation of the aryne was proposed based on DFT calculations. When alcohols were used we detected the oxidation of the alcohol rather than aryne products. The oxidized product was shown to not originate from arynes or a radical process but was formed via an intramolecular deprotonation from a 4-coordinated intermediate as suggested by DFT-calculations and experiments.In the final project we developed two complementary methods for the synthesis of phenols using hydroxide surrogates as nucleophiles. These compounds have previously been difficult to make using diaryliodonium salts due to aryne formation or overarylation to form diaryl ethers. The first method used hydrogen peroxide as the surrogate and allowed formation of electron-deficient and moderately electron-rich phenols. The synthesis of ortho-alkyl substituted phenols could be accomplished by using silanols as the surrogate. This allowed us to synthesize several highly congested phenols in good yields. Highly electron-rich diaryliodonium salts were, however, not compatible with either of the two methods.
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