Catalytic Reactions of Titanium Alkoxides with Grignard Reagents and Imines:A Mechanistic Study

The reactivity of Grignard reagents towards imines in the presence of catalytic and stoichiometric amounts of titanium alkoxides is reported.Alkylation, reduction, and coupling of imines take place. Whereas reductive coupling is the major reaction in stoichiometric reactions, alkylation is favored in catalytic reactions. Mechanistic studies clearly indicate that intermediates involved in the two reactions are different. Catalytic reactions involve a metal alkyl complex. This has been confirmed by reactions of deuterium-labeled substrates and different alkylating agents. Under the stoichiometric conditions, however, titanium olefin complexes are formed through reductive elimination, probably through a multinuclear intermediate.

Acylation of Grignard reagents mediated by N-methylpyrrolidone: A remarkable selectivity for the synthesis of ketones

An efficient user-friendly method of acylation of Grignard reagents to selectively synthesize ketones is presented, which is assisted by simple amides such as NMP, or DMF. The present chemoselective method tolerates a variety of functional groups such as ketone, ester, nitrile and other functional groups.

The chemistry of alpha-oxo ketene cyclic dithioacetal .36. Studies on silica G catalyzed decomposition of adducts of beta,beta-1,3-propylenedithio-alpha,beta-unsaturated arylketones with grignard reagents

beta, beta-1, 3-Piopylenedithio-alpha, beta-unsaturated arylketones 2 via chemoselective 1,2-addition with allyl or benzyl Grignard reagents afforded the corresponding carbinols 3 and 4. Catalysed by silica gel, the carbinols 3 and 4 were converted to the beta,gamma-unsaturated arylketones 5, 6. The mechanism and reaction condition were discussed.

Novel cross-coupling reactions between organotellurides and Grignard reagents employing a MnCl2/CuI catalytic system

We present a general protocol for the cross-coupling reaction of Grignard reagents and organic tellurides. Aryl Grignard reagents react stereospecifically with vinyl tellurides in the presence of a catalytic amount of manganese (II) chloride and copper (I) iodide to produce good yields of the corresponding cross-coupling products. (C) 2012 Published by Elsevier Ltd.

A G. C./M. S. study of the reaction and decomposition products of pentafluorophenyl-grignard and lithium reagents

Decomposition and side reactions of, and the synthetic use of, pentafluorophenylmagnesium bromide and pentafluorophenyllithium have been investigated using G,C9/M.S, techniques• Their reactions with reagents such as CgF^X (X - H, F, CI, Br, 1), C6F4X2 (X - H, CI)f C6F3C13, C6H6. (CgX5)3P (X = H, F), (C6X5)3P=0 (X = H, F), (CgX5)Si (CH3)3 (X = H, F) and (CH0K SiCl , n = 1,2, in ether or ether/n-hexane were studied• In addition to the principal reaction of synthetic use, namely the replacement of a halogen by a pentafluorophenyl group, two types of side reactions were observed* These were (i) intermolecular loss of LiF via a nucleophilic substitution, and (ii) intramolecular loss of LiF, followed by the addition of either inorganic salts such as lithium or magnesium halides, or organometal compounds such as organolithium or organo-Grigaard* G.C«/M.S. techniques were routinely employed to study complicated reaction mixtures. Although mass spectrometry alone has disadvantages for the identification of isomers, deduction of the most probable pathway often helps overcome this problem.

I. The effect of N,N,N',N' -tetramethylethylenediamine on the Schlenk Equilibrium. II. The nature of the Di-Grignard reagent

I. The influence of N,N,N’,N’-tetramethylethylenediamine on the Schlenk equilibrium

The equilibrium between ethylmagnesium bromide, diethylmagnesium, and magnesium bromide has been studied by nuclear magnetic resonance spectroscopy. The interconversion of the species is very fast on the nmr time scale, and only an averaged spectrum is observed for the ethyl species. When N,N,N’,N’-tetramethylethylenediamine is added to solutions of these reagents in tetrahydrofuran, the rate of interconversion is reduced. At temperatures near -50°, two ethylmagnesium species have been observed. These are attributed to the different ethyl groups in ethylmagnesium bromide and diethylmagnesium, two of the species involved in the Schlenk equilibrium of Grignard reagents.

II. The nature of di-Grignard reagents</p>

Di-Grignard reagents have been examined by nuclear magnetic resonance spectroscopy in an attempt to prove that dialkylmagnesium reagents are in equilibrium with alkylmagnesium halides. The di-Grignard reagents of compounds such as 1,4-dibromobutane have been investigated. The dialkylmagnesium form of this di-Grignard reagent can exist as an intramolecular cyclic species, tetramethylene-magnesium. This cyclic form would give an nmr spectrum different from that of the classical alkylmagnesium halide di-Grignard reagent. In dimethyl ether-tetrahydrofuran solutions of di-Grignard reagents containing N N,N,N’,N’-Tetramethylethylenediamine, evidence has been found for the existence of an intramolecular dialkylmagnesium species. This species is rapidly equilibrating with other forms, but at low temperatures, the rates of interconversion are reduced. Two species can be seen in the nmr spectrum at -50°. One is the cyclic species; the other is an open form.

Inversion of the carbon at the carbon-magnesium bond in di-Grignard reagents has also been studied. This process is much faster than in corresponding monofunctional Grignard reagents.

Diastereoselective Addition of Arylzinc Reagents to Sugar Aldehydes

The diastereoselective arylation of sugar-derived aldehydes is described. The arylating reagents are generated in situ by a boron-to-zinc exchange reaction of arylboronic acids with Et2Zn to generate arylethylzinc reagents. The exquisite reactivity of the arylzinc reagents allowed for an efficient and mild arylation, delivering the corresponding products in diastereolsomeric ratios of up to >20:1. The utility of the methodology is highlighted with an efficient formal synthesis of (+)-7-epl-goniofufurone, a member of the styryllactone family of natural products.

Synthesis and characterization of phenylene-thiophene all-conjugated diblock copolymers

Grignard metathesis (GRIM) polymerization for all-conjugated diblock copolymers comprising poly (2,5-dihexyloxy-1,4-phenylene) (PPP) and poly(3-hexylthiophene) (P3HT) blocks were systematically studied with LiCl as additive and 1,2-bis (diphenylphosphino) ethane nickel dichloride (Ni(dppe)Cl-2) or 1,3-bis(diphenylphosphino) propane nickel dichloride (Ni(dppp)Cl-2) as catalyst. It was found that the addition order of the monomers was crucial for the success of copolymerization. With the monomer addition in the order of phenyl and then thienyl Grignard reagents, all-conjugated PPP-b-P3HT diblock copolymers with different block ratios were successfully synthesized. In contrast, the inverted addition order only afforded a mixture containing both block copolymers and deactivated or end-capped homopolymers.

Design, synthesis and evaluation of novel ellipticine derivatives and analogues as anti-cancer agents

This thesis describes work carried out on the synthesis of novel 5- and 11-substituted ellipticines and derivatives of the ellipticine analogues, isoellipticine and deazaellipticine, followed by investigation of their potential as anti-cancer agents. Preparation of the key 5- and 11-substituted ellipticine targets involved the development of regiospecific, sequential alkylation reactions with alkenyllithium and Grignard reagents. Investigation of these novel reactions resulted in a new route towards 5-substituted ellipticines via Grignard reaction with vinylmagnesium bromide. These novel 5-vinylellipticine derivatives were further functionalised in an ozonolysis reaction, followed by oxidation to give a range of novel 5-substituted ellipticines. Less success was encountered in the 11-substituted ellipticine series, however preparation of these derivatives using a previously published route was accomplished, and the resulting 11-formylellipticine was further derivatised to give a panel of novel 9- and 11-substituted ellipticines, incorporating amide, carboxylate, imine and amine functionality. The successful route towards 5-substituted ellipticines was applied to the preparation of a range of novel 11-substituted isoellipticines and 6-substituted deazaellipticines, the first time substantial synthesis has been undertaken with these analogues. In addition to this, the first preparation of isoellipticinium salts is described, and a panel of novel isoellipticinium, 7 formylisoellipticinium and 7-hydroxyisoellipticinium salts were synthesised in good yields. Biological evaluation of a panel of 43 novel ellipticine, isoellipticine and deazaellipticine derivatives was accomplished with a topoisomerase II decatenation assay and submission to the NCI 60-cell line screen. Four novel isoellipticine topoisomerase II inhibitors were identified from the decatenation assay, with strong activity at 10 μM. In addition to this, NCI screening identified five highly cytotoxic ellipticine and isoellipticine compounds with remarkable selectivity profiles for different cancer types. These novel lead compounds represent new templates for further research and synthesis.

Precursor chemistry for oxide related materials

This thesis describes modelling, synthesis, spectroscopic and physical characterisation, as well as application of Magnesium, Calcium and Copper β-diketonate, β-ketoiminate, β-diiminate, Schiff base, amide and fluorenyl compounds. The selected compounds could potentially find application in materials deposition using Atomic Layer Deposition (ALD), MOCVD, CVD and Sol-Gel techniques. Quantum chemical modelling was used as a tool to perform the comprehensive and rapid study of magnesium and calcium precursor molecules in order to predict which of them would be more successful in ALD of metal oxides. Precursor chemistry plays a key role in ALD, since precursors must be volatile, thermally stable, chemisorb on the surface and react rapidly with existing surface groups. This Thesis describes one aspect of this, surface reactivity between ligands and hydroxyl groups, via a gas-phase model with energetics computed at the level of Density Functional Theory (DFT). A number of different synthetic strategies, both aerobic and anaerobic, were investigated for the synthesis of the described metal complexes. These included the use of different metal starting reagents such as, anhydrous and hydrated inorganic metal salts, metal alkyls and Grignard reagents. Some of previously unreported metal complexes of homoleptic and heteroleptic magnesium, calcium and copper β-diketonates, β-ketoiminates, β-diiminates, amides and Schiff base type were synthesised and characterised: [Mg(hfpd)2(DipPa)], [Mg(hfpd)2(MapH)2], [Mg(hf-ebp)(THF)2], [Mg(tf-Pap)Cl(THF)2], [Ca(PhNacnac)2], [Cu(tf-Pap)2], [Cu(PhNacnac)2], [Cu(hf-ebp)], [Cu(DipPa)] and [Cu(DipPa)2(4,4’-bypy)]. A comprehensive study on the thermal properties of magnesium, calcium and copper β-diketonates, β-ketoiminates, β-diiminates, Schiff base, amide and fluorenyl complexes was performed using TGA and sublimation of selected compounds. Atomic Layer Deposition of MgO using magnesium β-ketoiminate – [bis{(4-N-phenyl)-2-pentonato} magnesium] and β-diketonate - [bis(1,1,1,5,5,5-hexafluoropentane-2,4-dionato)(THF)magnesium hydrate] was performed on Si(100) substrates at 180°C and 0.2 Torr using O2 plasma.

Synthèse stéréosélective de dérivés pipéridines polysubstitués par fragmentation de Grob

Dans ce mémoire, il sera question de la formation de dérivés pipéridines en utilisant la fragmentation de Grob. Tout d’abord, une introduction sur les alcaloïdes ainsi que sur l’expertise du groupe Charette associée à leur formation démontrera l’importance de ces composés dans le domaine de la chimie organique. Cela sera suivi par un résumé de la fragmentation de Grob incluant les conditions de réactions utilisées, l’importance de la structure de la molécule initiale, les prérequis stéréoélectroniques ainsi que les modifications qui y ont été apportées. Le chapitre 2 sera dédié au développement de la méthodologie c’est-à-dire, à l’optimisation de tous les paramètres jouant un rôle dans la fragmentation de Grob. Par la suite, l’étendue de la réaction ainsi que des explications sur la régiosélectivité et la diastéréosélectivité de la réaction seront fournies. La méthodologie peut être exploitée dans un contexte de synthèse qui sera démontré dans le chapitre 3. De plus, elle servira pour une étude mécanistique qui est encore d’actualité à partir du concept d’effet frangomérique. Finalement, quelques projets futurs, notamment des améliorations possibles de la méthodologie, seront présentés dans le dernier chapitre. Le tout sera suivi d’une conclusion résumant l’ensemble des travaux effectués.

Synthèse et analyse conformationelle de dipeptides contenant l’isostère hydroxyéthylène

Dans ce mémoire, je présente mes études sur une stratégie efficace développée pour la synthèse de cétones homoallyliques substituées à partir de l’addition en cascade de réactifs de Grignard vinyliques substitués sur des α-amino esters catalysée par des sels de cuivre. L’utilisation de ces cétones homoallyliques a permis d’obtenir des mimes peptidiques comprenant un isostère de type hydroxyéthylène du lien amide. L’étape clé de cette stratégie repose sur la synthèse de cétones homoallyliques substituées intermédiaires à partir de la réaction d’additions en cascade catalysée au cuivre, de bromure de β,β-diméthylevinyle magnésium sur des analogues d’esters de la phénylalanine et de la sérine. Les cétones homoallyliques résultantes sont réduites sélectivement en alcool, la liaison double est clivée oxydativement et l’acide carboxylique résultant est couplé à un acide aminé. Afin d’évaluer l’effet qu’ont le remplacement du lien amide central dans un coude β par un hydroxyéthylène et de la présence d’un gem diméthyle sur la chaîne carbonée sur la conformation tridimensionnelle adoptée par les tripeptides générés, des analyses à l’état solide par diffraction aux rayons X, des analyses en solution par la spectroscopie RMN et des expériences de type NOESY ont été réalisées. Ces études ont permis de définir un nouveau type de coude β. La présence de pont hydrogène intramoléculaire et l’effet de restriction de conformation induit par le gem diméthyle, généralement appelé effet Thorpe-Ingold, favorisent la formation d’un coude β.

Preparation and ring-opening reactions of N,O-bis(diphenylphosphinyl) hydroxymethylaziridine ('Di-Dpp')

N,O-bis(diphenylphosphinyl)-2-(hydroxymethyl)aziridine ('DiDpp', 1) is efficiently prepared from 2-aminoethane-1,3-diol: this activated aziridine undergoes two sequential reactions with copper(I)-modified Grignard reagents, yielding alpha-branched N-Dpp amines in good yield. (C) 2003 Elsevier Science Ltd. All rights reserved.