No description available.

A series of closely related lithium aryl thiolates with pyridine as a donor ligand have been prepared. X-ray structure determination (Dr. W. Clegg) has shown that [PKSLi.(NC(_5)H(_5))] crystallises as an infinite chain polymer. Insertion of a methylene group between the phenyl ring and sulphur as in (PhCH(_2)SLi .NC(_5)H(_5). ] (_oo) produced an infinitely folded ladder polymer with Li-S rungs, while introduction of an 0-methyl group produces the monomeric complex [o-MeC(_6)H(_4)SLi .(NC(_5)H(_5))(_3)].The unusual symmetrical complex [Li(_14) (SCH(_2)Ph)(_12) S(TMEDA.)(_6)] has been prepared, in which a central sulphur atom is surrounded by a distorted cube of lithium atoms, each edge of which is bridged by a benzyl thiolate group such that the twelve S atoms form a cubo- octahedron: a further six Li atoms form a larger outer octahedron. When TMEDA is present in excess it appears that both PhSLi and PhCH(_2)SLi form dimeric compounds with a central Li(_2)S(_2) ring but structure determination of these complexes is incomplete.[PhOOSLi.TMEDA](_2)has been prepared and crystallises as a centrosymmetric dimer containing a chair shaped central eight membered (OOSLi)(_2) ring with the Li atoms out of the (COS)(-2), molecular plane. Lithiation of the related acids PhOOOH and PhCSSH has been carried out in the presence of TMEDA but crystal growth has so far been unsuccessful. Ab initio m.o. calculations on related model compounds are included. A preliminary study has been carried out on the lithiation of the thio-oxime (Ph(_2) C-NSH). Results were encouraging but detailed investigation is needed. The reaction of S(_4) N(_4) with BI(_3) produces, not the expected adduct, S(_4)N(_4) .BI(_3) , but an intractable polymer, empirical formula, S(_3)N(_3)BI. Other adducts of S(_4).N(_4) and (PhCN_2) S(_2))(_2), were prepared but were unsuitable for further reactions. The reaction of lithium borohydride and sulphur in THF to produce sulphurated lithium borohydride has been modified to give a controllable reaction. Further reaction with TMEDA gives clear orange crystals of a complex the composition of which is still unknown.

Thesis (Ph. D.)--University of Missouri--Columbia, 2000. / "August 2000." Typescript. Vita. Includes bibliographical references (leaves 113-122). Also available on the Internet.

Thesis (Ph. D.)--University of Washington, 2005. / Vita. Includes bibliographical references (leaves 170-186).

No description available.

This master thesis deals with the preparation of β-cyclodextrin derivatives which can be attached on gold surface via methylsulfanyl groups. The thesis particularly deals with the preparation and characterization of mono-aryl-per-6-(methylsulfanyl) derivatives of β-cyclodextrin prepared from corresponding monopropragyl derivative. This work also deals with the attachment of per-6-deoxy-per-6-methylsulfanyl-β- cyclodextrin to gold surface of quartz crystal microbalances. Keywords: β-cyclodextrin, methylsulfanyl derivatives, propargyl derivatives, cyclodextrin derivatization, click reaction

The general biosynthetic pathway for tryptophan is known. However, little information has been gathered on how substrates and enzymes interact when phosphoribosylanthranilate isomerase (PRAI) and indole-3-glycerolphosphate synthase (IPGS) convert a substituted phenyl ring, PRA, into an indole moiety, IGP, via 1-(O-carboxyphenylamino)-1-deoxyribulose-5-phosphate (CdRP). There has been no serious synthetic approach to develop methodology to produce a plethora of substrate and product analogues of CdRP. The studies described in this thesis cover methodology focusing on secondary aryl amine formation, using reductive amination, nucleophilic substitution and epoxide ring opening, leading to CdRP analogues. Reductive aminations with D-ribose failed to produce any aryl glycosylamine precursor, possibly due to the low nucleophilicity of aryl amines such as aniline. Removing the aromaticity and using cyclohexylamine produced secondary amines in moderate yield in the presence of benzylpentanal, and NaBH3CN, at a pH of 5.5. This led to a successful reductive amination using anthranilate methyl ester. Secondary aryl amine synthesis via epoxide ring opening proved consistently reproducible. Using LiNTf2 and high equivalents of cyclohexylamine or aniline in neat conditions opened protected epoxides. This has led to the formation of advanced secondary aryl amine synthons and the development of methodology leading to target compounds with functionality at the 1,2 and 5 positions. Nucleophilic substitution using caesium base, high equivalents aniline at room temperature, gave a moderate yield of secondary aryl amines from sulfonyl and bromide good leaving groups. Raising the reaction temperature improved yields using low equivalents of aniline, with the optimal temperature being 50 °C. Ultimately using both the high equivalents of aniline or anthranilate methyl ester and warming the reaction in DMF gave the highest yields of secondary aryl amines. No overalkylated tertiary amine was isolated when a caesium base was used. Boc N-protection of 1-phenylamino-4-pentene and asymmetric dihydroxylation gave the corresponding diol, which was phosphorylated giving the protected target 1,4,5 compound. The methodology leading to the protected target 1,4,5 compound synthesis provides a means to the synthesis additional of CdRP analogues.

No description available.

This thesis describes studies of a "kinetic template effect" which assists the formation of arylphosphonium salts from aryl halides and tertiary phosphines in the presence of a transition metal halide catalyst in refluxing ethanol. The "kinetic template effect" arises from the presence in the aryl halide of a limited range of orthosubstituents capable of intramolecular coordination with the metal at a critical stage of the reaction. In Chapter One, the "kinetic template effect" is compared with the better known "thermodynamic template effect". Earlier work on related "kinetic template effects" in the formation of aryl-phosphorus bonds is reviewed. The evidence for the possible involvement of aryl-metal intermediates in such reactions is also discussed. Chapter Two is concerned with the design and synthesis of potential template molecules. A model is proposed for the features necessary in the template substituent in terms of the nature and position of the donor atom or group essential for the replacement of the ortho-halogen under mild conditions. Chapter Three describes a kinetic study of the nickel (II) catalysed reactions of ortho-haloaryl Schiff's base and ortho-haloarylazo-dyestuff templates with tertiary phosphines. A rate law is deduced which indicates a first order dependence in each reactant, i.e. rate a [template] [phosphine] [catalyst], an overall third order expression. Rate studies also indicate that the nature of the orthohalogen is important, the order of replacement being I > Br > Cl. The effects of substituents remote from the ortho-haloaryl template are also considered. A mechanistic scheme consistent with the rate data is proposed. The X-ray crystal structures of two arylphosphonium salts derived from template aryl halides are discussed in Chapter Four, providing unequivocal proof that the position of replacement of halogen in substrates bearing more than one replaceable halogen, in different positions, is ortho with respect to the template donor group.

It is generally acknowledged that polyfluoroarenes are important fluorinated structural units for various organic molecules, such as pharmaceuticals, agrochemicals, and organic materials. Polyfluorinated aryl alkynes and alcohols are also powerful building blocks in chemical synthesis because of their versatility to be transformed into various useful molecules and also their ubiquity in natural product synthesis. Efficient methods for the synthesis of polyfluorinated aryl alkynes and alcohols are presented in Chapter 2 and Chapter 3. In addition, 3-amino-indoles have found a broad applications in medicinal chemistry as effective anticancer agents, compounds with analgesic properties and can function as potent inhibitors of tubulin polymerization, and agents for the prevention of type II diabetes. A simple method for the synthesis of 3-amino-indoles via the annulation reaction of polyfluorophenylboronates with DMF is reported in Chapter 4. Chapter 2 In Chapter 2, a mild process for the copper-catalyzed oxidative cross-coupling of electron-deficient polyfluorophenylboronate esters with terminal alkynes (Scheme S-1) is reported. This method displays good functional group tolerance and broad substrate scope, generating cross-coupled alkynyl(fluoro)arene products in moderate to excellent yields. This copper-catalyzed reaction was conducted on a gram scale to generate the corresponding product in good yield (72%). Scheme S-1. Copper-catalyzed oxidative cross-coupling of terminal alkynes with polyfluorophenylboronate esters. Based on previous reports and the aforementioned observations, a plausible catalytic cycle for this oxidative cross-coupling reaction is shown in Scheme S-2. The first step involves the addition of an alkynyl anion to Cu leading to the formation of alkynylcopper(II) species B. Subsequent transmetalation between ArFBpin and intermediate B occurs to form intermediate C. The desired product 3a is generated by eductive elimination. Finally, the oxidation of Cu(0) to Cu(II) with DDQ and Ag2O regenerates A to complete the catalytic cycle. Scheme S-2. Proposed mechanism of copper(II)-catalyzed oxidative cross-coupling between terminal alkynes and polyfluorophenylboronate esters. Chapter 3 In Chapter 3, A convenient and efficient protocol for the transition metal-free 1,2-addition of polyfluoroaryl boronate esters to aldehydes and ketones is reported, which provides secondary alcohols, tertiary alcohols, and ketones (Scheme S-3). The distinguishing features of this procedure include the employment of commercially available starting materials and the broad scope of the reaction with a wide variety of carbonyl compounds giving moderate to excellent yields. Scheme S-3. Base-promoted 1,2-addition of polyfluorophenylboronates to aldehydes and ketones. Control experiments were carried out to gain insight into the reaction mechanism. The reaction of 2a with pentafluorobenzene 5 under standard conditions was examined, yet 3a was not formed in any detectable amounts (Scheme S-4a), indicating that the C-Bpin moiety is essential and deprotonation of the fluoroarene or nucleophilic attack at the fluoroarene by the base is not a plausible pathway. Interestingly, for the standard reaction between 1a and 2a, the yield dropped dramatically if 18-crown-6 ether and K2CO3 were added (Scheme S-4b). This experimental result indicates that the presence of the potassium ion plays a crucial role for the outcome of the reaction. Furthermore, if the reaction of 1a and 2a was performed in the presence of only a catalytic amount of K2CO3 (20 mol%) (Scheme S-4c), reaction rates were reduced, and a week was required to produce 3a in good yield. This finding again indicates that the potassium ion (or the base) plays an important role in the reaction. Substituting ortho-fluorines by ortho-chlorines, using either C6Cl5Bpin 2,6-dichlorophenyl-1-Bpin as substrates, did not yield any product as shown by in situ GCMS studies. Scheme S-4. Control experiments. Based on DFT calculations, a mechanism for the 1,2-addition of polyfluorophenylboronates to aryl aldehydes in the presence of K2CO3 as base is proposed, as shown in Scheme S-5. K2CO3 interacts with the Lewis-acidic Bpin moiety of substrate 1 to generate base adduct A, which weakens the carbon-boron bond and ultimately cleaves the BC bond along with attachment of a potassium cation to the aryl group. The resulting ArF- anion adduct B undergoes nucleophilic attack at the aldehyde carbon atom of substrate 2 to generate methanolate C. The methanolate oxygen atom then attacks the electrophilic Bpin group to obtain compound D. Transfer of K2CO3 from intermediate D to the boron atom of the more Lewis-acidic polyfluorophenyl-Bpin 1 finally closes the cycle and regenerates complex A. Thus, the primary reaction product is the O-borylated addition product E, which was detected by HRMS and NMR spectroscopy for the perfluorinated derivative. Scheme S-5. Proposed mechanism of the 1,2-addition of polyfluorophenylboronates to aldehydes and ketones. Chapter 4 Chapter 4 presents a novel protocol for the transition metal-free addition and annulation of polyfluoroarylboronate esters to DMF, which provides 3-aminoindoles and tertiary amines in moderate to excellent yields (Scheme S-6). Scheme S-6. Annulation and addition reactions of polyfluorophenylboronates with DMF. While exploring the application of this strategy in synthesis, perfluorophenylBpin reacted smoothly with ethynylarenes and DMF to afford propargylamines with moderate to excellent yields (Scheme S-7). Scheme S-7. Three-component cross-coupling reaction for the synthesis of propargylamines. / Polyfluorarene sind wichtige fluorierte Schlüsselstruktureinheiten für verschiedene organische Moleküle, wie z. B. Pharmazeutika, Agrochemikalien und organische Materialien. Auch polyfluorierte Arylalkine und -alkohole sind aufgrund ihrer vielseitigen Möglichkeiten, in verschiedene nützliche Moleküle umgewandelt zu werden als auch wegen ihrer Allgegenwart in der Naturstoffsynthese, leistungsfähige Bausteine. Effiziente Methoden zur Synthese polyfluorierter Arylalkine und -alkohole werden in Kapitel 2 und Kapitel 3 vorgestellt. Darüber hinaus haben 3-Amino-Indole eine breite Anwendung in der medizinischen Chemie als wirksame Antikrebsmittel, Verbindungen mit analgetischen Eigenschaften und als potente Inhibitoren der Tubulinpolymerisation sowie als Mittel zur Prävention von Typ-II-Diabetes gefunden. Eine einfache Methode zur Synthese von 3-Amino-Indolen über die Annulierungssreaktion von Polyfluorphenylboronaten mit DMF wird in Kapitel 4 berichtet. Kapitel 2 In Kapitel 2 wird über ein mildes Verfahren zur kupferkatalysierten oxidativen Kreuzkupplung von elektronenarmen Polyfluorphenylboronatestern mit terminalen Alkinen (Schema S-1) berichtet. Diese Methode zeichnet sich durch eine gute Toleranz gegenüber funktionellen Gruppen und eine große Bandbreite an Substraten aus und erzeugt kreuzgekoppelte Alkinyl(fluor)aren-Produkte in moderaten bis exzellenten Ausbeuten. Diese kupferkatalysierte Reaktion wurde im Gramm-Maßstab durchgeführt, und erzeugt das entsprechende Produkt in guter Ausbeute (72 %). Schema S-1. Kupfer-katalysierte oxidative Kreuzkupplung terminaler Alkine mit Polyfluorphenylboronatestern. Basierend auf früheren Arbeiten und den oben erwähnten Beobachtungen ist ein plausibler katalytischer Zyklus für diese oxidative Kreuzkupplungsreaktion in Schema S-2 dargestellt. Der erste Schritt beinhaltet die Addition eines Alkinylanions, was zur Bildung des Alkinylkupfer(II)-Komplexes B führen sollte. Anschließend erfolgt eine Transmetallierung zwischen ArFBpin und dem Zwischenprodukt B zur Bildung des Zwischenproduktes C. Das gewünschte Produkt 3a wirde dann daraus durch reduktive Eliminierung erzeugt. Durch eine Oxidation des dabei entstehenden Cu(0)-Komplexes mit DDQ und Ag2O wird Komplex A regeneriert und der katalytische Zyklus schließt sich. Schema S-2. Vorgeschlagener Mechanismus der Kupfer(II)-katalysierten oxidativen Kreuzkupplung terminaler Alkine und Polyfluorphenylboronatestern. Kapitel 3 In Kapitel 3 wird ein praktisches und effizientes Protokoll für die übergangsmetallfreie 1,2-Addition von Polyfluorarylboronatestern an Aldehyde und Ketone vorgestellt, welches sekundäre Alkohole, tertiäre Alkohole und Ketone liefert (Schema S-3). Die besonderen Merkmale dieses Verfahrens sind die Verwendung kommerziell erhältlicher Ausgangsmaterialien und die große Bandbreite der Reaktion mit einer Vielzahl von Carbonylverbindungen, die mäßige bis exzellente Ausbeuten erbringen. Schema S-3. Basen-unterstützte 1,2-Addition von Polyfluorphenylboronaten an Aldehyde und Ketone. Um einen Einblick in den Reaktionsmechanismus zu erhalten, wurden Kontrollexperimente durchgeführt. Die Reaktion von 2a mit Pentafluorbenzol 5 unter Standardbedingungen wurde untersucht, jedoch wurde 3a nicht in nachweisbaren Mengen gebildet (Schema S-4a). Dies deudet darauf hin, dass der C-Bpin Anteil essenziell ist und eine Deprotonierung des Fluorarens oder ein nukleophiler Angriff am Fluoraren durch die Base kein plausibler Weg ist. Interessanterweise sank bei der Standardreaktion zwischen 1a und 2a die Ausbeute dramatisch, wenn 18-Kronen-6-Ether und K2CO3 zugesetzt wurden (Schema S-4b). Dieses experimentelle Ergebnis belegt, dass die Anwesenheit des Kalium-Ions eine entscheidende Rolle für den Ausgang der Reaktion spielt. Wenn die Reaktion von 1a und 2a in Gegenwart von nur einer katalytischen Menge K2CO3 (20 mol%) durchgeführt wurde (Schema S-4c), waren die Reaktionsgeschwindigkeiten geringer und es war eine Woche erforderlich, um 3a in guter Ausbeute zu erlangen. Dieser Befund weist erneut darauf hin, dass das Kalium-Ion (oder die Base) eine wichtige Rolle bei der Reaktion spielt. Die Substitution von ortho-Fluorsubstituenten durch ortho-Chlorsubstituenten, wobei entweder C6Cl5Bpin oder 2,6-Dichlorphenyl-Bpin als Substrate verwendet wurden, lieferte kein Produkt, wie in situ GCMS-Studien zeigten. Schema S-4. Kontrollexperimente. Ein Vorschlag zum Mechanismus der 1,2-Addition von Polyfluorphenylboronaten an Arylaldehyde in Gegenwart von K2CO3 als Base wird in Schema S-5 vorgeschlagen. Dabei wechselwirkt die Base K2CO3 mit der Lewis-sauren Bpin-Einheit des Substrats 1 unter Ausbildung des Basenadduktes A, in welchem die Kohlenstoff-Bor-Bindung geschwächt ist und schließlich die B-C Bindung gespalteen wird, wobei sich ein Kaliumkation an die Arylgruppe anlagert. Das resultierende ArF- Anion im Addukt B greift nukleophil am Aldehyd-Kohlenstoffatom von Substrat 2 an, um Methanolat C zu erzeugen. Das Methanolat-Sauerstoffatom reagiert dann mit der elektrophilen Bpin-Gruppe, um Verbindung D zu erhalten. Die Übertragung von K2CO3 vom Zwischenprodukt D auf das Boratom des Lewis-acideren Polyfluorphenyl-Bpin 1 schließt schließlich den Zyklus und regeneriert den Komplex A. Das primäre Reaktionsprodukt ist also das O-borylierte Additionsprodukt E, das mittels HRMS und NMR-Spektroskopie für das perfluorierte Derivat nachgewiesen wurde. Schema S-5. Vorgeschlagener Mechanismus der 1,2-Addition von Polyfluorphenylboronaten an Aldehyden und Ketonen. Kapitel 4 In Kapitel 4 wird ein neuartiges Protokoll für die übergangsmetallfreie Addition und Annulierungsreaktion von Polyfluorarylboronatestern an DMF vorgestellt, das 3-Aminoindole und tertiäre Amine in mäßigen bis ausgezeichneten Ausbeuten liefert(Schema S-6). Schema S-6. Annulierungs- und Additionsreaktion von Polyfluorphenylboronaten mit DMF. Bei der Erkundung der Anwendung dieser Strategie in der Synthese konnten Propargylamine mit mäßigen bis ausgezeichneten Ausbeuten hergestellt werden (Schema S-7). Schema S-7. Kreuzkupplungsreaktion für die Synthese von Propargylaminen.