The purpose of this study was to develop new catalytic methods to mediate carbon-carbon bond forming reactions with imines under mild conditions and in a general manner. We found that copper catalysts were compatible in cross-coupling of a range of mild organometallic reagents, providing simple, efficient routes to alpha-substituted amides and amines. / Chapter 2 of this thesis describes a new copper-catalyzed multicomponent synthesis of alpha-substituted amides. This reaction was developed based upon previous work in this laboratory, which showed that palladium catalysts were competent in Stille-type cross-coupling of imines, acid chlorides, and organostannanes. While providing a mild method of generating the amide products, a more general procedure able to incorporate a wider range of organostannanes was sought. This chapter details the development of a copper-catalyzed protocol, which, as well as performing the cross-coupling under mild reaction conditions, proceeds with a diverse range of aryl-, heteroaryl-, and vinyl-substituted organostannanes and employs an inexpensive and readily available catalyst. Through this system, control over regioselectivity of addition to alpha,beta-unsaturated imines is also possible. / Chapter 3 demonstrates that, in addition to organostannanes, other substrates are viable in copper-catalyzed cross-coupling with imines and acid chlorides. Herein, the coupling of terminal alkynes with imines and acid chlorides is described, leading to an efficient synthesis of tertiary propargylamides directly from simple starting materials. This synthesis incorporates a wide variety of substituted imines, acid chlorides/chloroformates, and terminal alkynes, providing a rapid synthesis of these useful building blocks (reaction completion in only 15 minutes). In addition, the process is shown to work with aza-aromatic heterocycles, such as pyridine, where the alkynylation occurs exclusively at the 2-position. / Chapter 4 describes the utility of these rapid multicomponent reactions, where the products are directly converted into oxazole heterocycles. Copper-catalyzed- and zinc-catalyzed protocols are developed for the synthesis of secondary propargylamides from silyl-imines, acid chlorides, and terminal alkynes. The secondary propargylamide products are then, in a one pot sequence, transformed into trisubstituted oxazoles. / Chapter 5 describes the development of an atom-economical, non-toxic alternative to the organotin coupling described in Chapter 2. This involves the use of tri- and tetraorgano-indium reagents, which can transfer all of their organic groups in a copper-catalyzed coupling with imines and acid chlorides. This reaction shows good functional group compatibility and further expands the scope of alpha-substituted amides and N-protected amines that can be synthesized through mild copper catalysis. / Chapter 6 explores the enantioselective alkynylation of nitrogen-containing heterocycles. As described in Chapter 3, heterocycles such as pyridine can undergo copper-catalyzed 1,2-addition with terminal alkynes upon activation by chloroformates. As this process generates a stereocenter, it is possible to introduce enantio-control into the reactions by using a chiral copper catalyst. With ligands from the PINAP series, enantioselectivities of up to 84% can be induced in the coupling of nitrogen-containing heterocycles (e.g., quinoline), chloroformates, and terminal alkynes. This provides a mild and simple synthesis of chiral 2-alkynyl-1,2-dihydroquinolines directly from simple starting materials.

No description available.

Photocopy of typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1980. / Bibliography: leaves 125-126. / Microfiche. / x, 126 leaves, bound 28 cm

Thesis (Ph. D.)--University of Hawaii at Manoa, 1995. / Includes bibliographical references (leaves 124-127). / Microfiche. / xi, 127 leaves, bound ill. 29 cm

Typescript. / Thesis (Ph. D.)--University of Hawaii at Manoa, 1976. / Bibliography: leaves [312]-320. / Microfiche. / xxx, 320 leaves ill

This thesis documents the development of novel methodologies for access to sulfur-containing compounds, including sulfones, sulfonamides and benzoisothiazoles. <b>Chapter 1</b> provides an overview of the applications and the synthesis of sulfonyl-containing compounds. A comprehensive introduction to the development of sulfur dioxide surrogates and their applications in transition metal-catalysed organic chemistry is given. <b>Chapter 2</b> describes the development of a one-step copper(I)-catalysed sulfonylative Suzuki-Miyaura cross coupling reaction. A wide range of aryl and alkenyl boronic acids are coupled with aryl and alkenyl iodides to give the corresponding sulfones. A two-step one-pot sulfination/derivatisation method was also developed, allowing access to compounds including β-hydroxy sulfones, sulfonamides and sulfonyl fluorides. <b>Chapter 3</b> illustrates a one-step copper(II)-catalysed sulfonamide synthesis using boronic acids, amines and SO2. Various aryl and alkenyl boronic acids as well as amines and anilines are compatible, including active pharmaceutical ingredients such as amoxapine and desloratadine. <b>Chapter 4</b> details an aryne-based selective formation of substituted benzoisothiazoles. Different substitution pattern of the aryne precursor and the thiadiazole are employed, with the target heterocycles being obtained in good to excellent yields. <b>Chapter 5</b> summarises the research and the future work. <b>Chapter 6</b> documents the experimental procedures and data.

Transition metal-catalysed cross coupling chemistry is a valuable tool for synthetic organic chemistry, enabling the preparation of compounds of great interest. The catalytic metal of choice is usually palladium, which generally offer better performances in term of catalytic activity and easy handling. On the other hand, the use of nickel in this class of reactions is gaining attention, as it would provide more economically and environmentally sustainable processes. Deprotonative cross couplings are a subgroup of these reactions, in which the nucleophile is generated in situ by direct deprotonation of a (relatively) acidic C–H bond, for example those of an enolizable ketone or an imine. The reaction products often represent intermediates towards more complex molecular architectures, by virtue of the well-known carbonyl chemistry. The development of a Pd-catalysed methodology for the prototypical deprotonative coupling, the a-arylation of ketones, is reported in this thesis. It requires significantly lower catalyst loadings compared to previous reports, and displays good tolerance towards functionalised substrates. A related protocol for the intramolecular a-arylation of imines towards indoles was subsequently disclosed: as it requires low catalyst loadings and displays good scalability and simple setup, this methodology is a promising hit for industrial applications. The parallel development of nickel-catalysed protocols afforded an efficient method for the a-arylation of ketones, using chloroarenes as electrophile for the first time in the literature. The method was further optimised for the synthesis of an intermediate towards a commercial medicinally active compound. Building up on these findings, the first nickel-catalysed protocol for the deprotonative arylation of benzylaminederived imines was also developed. Last, the first aqueous palladium-catalysed protocol for the a-arylation of ketones was investigated. The method proved flexible, showing excellent functional group tolerance: compounds containing base-sensitive functional groups, halogenated small-molecule drugs, and Boc-protected amino acids were all suitable substrates.

In an industrial application a GFAAS method for monitoring the Rh concentration in process streams is being used. Matrix effects are known to exist with the application of this technique; in fact, it was observed that different solvents lead to different results. Therefore, standard additions have to be employed for quantitative determinations, resulting in high costs and long analysis times. In an attempt to understand these interfering effects, fractional factorial designs were proposed to determine whether any GFAAS parameter was responsible for, or related to, the matrix effects. Seven GFAAS parameters were investigated: final temperature, ramp time and hold time of the transitions step (from the dry step); final temperature, ramp time and hold time of the ashing/pyrolysis step; ramp time of the atomisation step. The results showed that the matrix effects were not related to any specific parameter. A complete factorial design was implemented to demonstrate the fundamental role of the atomisation temperature. SEM analysis showed that the surface of the graphite tubes might be affected in different ways by different solvents. A Principal Component Analysis demonstrated that the matrix effects may be related to the viscosity and melting point of the solvents and may be independent of their molar mass. To identify the origins of these effects, an investigation on the link between the tube surface-sample matrix interactions and the physical properties of the matrices is recommended. Since GFAAS parameters cannot compensate for the matrix effects, standard additions remain the preferred mode of operation as it accounts for the effects in-situ. / Chemistry / M.Sc. (Chemistry)

Ph.D. / The first part of the research described in this thesis involves the development of a new methodology for the synthesis of N-hydroxy pyrrolidines, starting from carbohydrates as building blocks. The products were identified as possible synthons for the stereocontrolled synthesis of isosteric analogues of polyhydroxylated indolizidine alkaloids. The consecutive reduction and cyclisation of selectively protected 5-0-mesyl hexose O-(tert-butyldiphenylsilyl) oximes to afford chiral N-hydroxy pyrrolidines is discussed. The mechanism involves a cascade of neighbouring group participation steps by the O-benzoyl protecting groups. This protocol gave rise to novel chiral N-hydroxy pyrrolidines in good overall yield. The choice of leaving group as well as a labile oxime protecting group proved to be of great import in the outcome of the cyclisation reactions. The second part of the research concerns the ongoing development in our laboratories of the synthesis of analogues of biologically active compounds. In this regard, we were interested in synthesising the aza analogues of f3-C-nucleosides and f3-C-glycosides. Our strategy involves the synthesis of a D-ribose derived chiral cyclic nitrone as the key synthon. A facile route towards cyclic nitrones was developed starting from suitably protected hemiacetals of Dribofuranose. Readily available tri-O-benzyl-D-ribofuranose was allowed to react with hydroxylamine hydrochloride to afford an acyclic oxime. Selective silylation followed by iodonation at C-5 (with inversion of configuration) furnished the cyclisation precursor. Anhydrous TBAF-mediated desilylation and subsequent intramolecular nucleophilic attack afforded a cyclic nitrone in excellent yield. Following the same protocol, 2,3-isopropylidene-5- 0-trityl-D-ribofuranose was converted into the corresponding nitrone. The 1,3-dipolar cycloaddition reaction of a nitrone to an alkene is an extremely powerful synthetic method for the creation of complex heterocyclic structures. The reaction of the Dribose derived nitrones with a,(3-unsaturated carbonyl compounds furnished the corresponding cycloadducts in good diastereomeric excess. The exo-product was isolated as the major isomer in each case. The reaction of a variety of carbon nucleophiles, including a Grignard reagent, with the nitrones led to the formation of interesting p-C-glycoside analogues. One of the carbohydrate nitrones was also converted into its thymine C-nucleoside analogue. This work clearly shows that the construction of chiral cyclic nitrones from D-ribose derivatives is an extremely efficient and simple procedure. The final part of the work described in this thesis involve the construction of CD-ring analogues of the natural metabolite, streptonigrin. The use of metalation and palladium catalysed cross-coupling reactions were investigated for the synthesis of highly functionalised biaryls. The synthesis and crystal structure determination of [3-(tert-butoxycarbonylamino)-4- pyridyl]-trimethyltin(IV) is discussed. The Stille cross-coupling reaction between an electron rich arylstannane and an electron poor aryl halide proved to be the most successful. The use of co-catalytic copper(I) had a dramatic effect on the overall yield and rate of this Stille crosscoupling reaction. This methodology would , in principle, allow the construction of the natural product and appropriate structural analogues.

The phenolic resin chemistry is an old chemistry that started in the late 1800’s. A lot of research work to gain understanding of phenolic resins has been done and reported in literature. However, most of the studies are based on phenol novolac resins. It was necessary to acquire more knowledge on specifically o-cresol novolac (OCN) resins because of the interest in the production of these resins. The chemistry in question was new to Sasol and one of the major objectives of doing this work was to build in-house competency in this field. This was achieved by first investigating whether the available feed materials containing certain impurities can be used to synthesise o-cresol novolacs with set specifications of purity and physical characteristics. The suitability of the Sasol o-cresol in terms of its contamination with sulfur (which is sometimes found in relatively higher amounts due to operating conditions) was investigated. The results showed that the sulfur in o-cresol did not have a significant contribution in the sulfur of the OCN. Another contaminant, formic acid, an auto-oxidation product found in formalin solutions was also investigated. It was also observed that, at formic acid levels of up to 4000 ppm, there was no effect on the softening point of the OCN. Secondly, it was important to study and understand the effect of different reaction variables on the quality of the OCN resins. The effect of formaldehyde: o-cresol molar ratio was investigated, the softening point increased with the increase in the molar ratio. The effects of other reaction variables (catalyst, reaction time, temperature and formaldehyde feed rate) on the softening point of the OCN were also investigated using p-toluenesulfonic acid and oxalic acid as catalysts. With p-toluenesulfonic acid as a catalyst, the temperature had no effect on the softening point, while all the other variables showed an effect on this parameter. A softening point model was formulated, which predicted the softening point with 98% accuracy. With oxalic acid, only the amount of catalyst had an effect. In addition, the chemical structures of these compounds were studied using 13C-NMR spectroscopy. The focus was on the isomer distribution of the methylene linkages. / Prof. D.B.G. Williams