The purpose of this research was to form (2S, 3R)-2,3bis(3,4-dimethoxybenzyl) butyrolactone. A brief review of the main classes of lignans, their biosynthesis, biological activity and clinical utility is given in the first chapter. The main chemical synthesis routes to such compounds are also provided covering the six most commonly used routes including the Stobbe condensation. An overview of the use of <I>meso</I> compounds for the production of chiral synthons and use of the '<I>meso</I> <I>trick</I>' to enhance yields during chiral induction to <I>meso</I> substrates are discussed in chapter two. Construction of the basic C<SUB>18</SUB> lignan skeleton in chapter three is achieved <I>via</I> a double Stobbe condensation with preferential formation of the E-isomer at each stage. In the first step the Stobbe product is reduced to give the maleic anhydride. This resisted further reduction but reduction of the dimethyl maleate successfully gave the <I>meso</I> succinic anhydride with no <I>d/l</I> isomer formation. The formation of the target compound is described in chapter four. Reaction of the <I>meso</I> substrate with (+)-α-methylbenzylamine proceeded with chiral induction in 81% d.e. The use of chiral alcohols including 1-methol, 1-α phenyl ethylalcohol and S-(+)-methyl mandelate has also been examined showing widely varying diastereoselectivities. Conversion of (2S, 3R, αR)-N-(α-phenylethyl)- 2,3-bis(3,4-dimethoxybenzyl)butanedioic acid monoamide to the target dibenzyl butyrolactone has been readily achieved by reduction to the corresponding alcohol prior to lactonisation. Racemisation of (2S, 3R)-2,3-bis(3,4-dimethoxybenzyl) butyrolactone under basic conditions and comparison of the optical rotation values obtained with those in the literature allowed the absolute stereochemistry to be assigned. The attempted formation of picrostegane type lignans by non phenolic oxidative coupling is also described.

Chapter 1 reviews the field of asymmetric synthesis with special emphasis on stereoselective enolate formation and reaction. The physical and chemical characteristics of [2.2]paracyclophane derivatives and other planar chiral compounds are examined and their role in asymmetric synthesis mentioned. Chapter 2 investigates the role of [2.2]paracyclophanes as planar chiral auxiliaries. The stereoselective production and α-substitution of [2.2]paracyclophane ester enolates is investigated. Chapter 3 introduces the field of boron stabilised carbanion chemistry and investigates the diastereoselective synthesis of <I>erythro</I>-1,2-diols by condensation/oxidation of boron stabilised carbanions with aromatic aldehydes. Phenylboronates are generated from the 1,2-diols in an attempt to determine stereochemistry.

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Polysubstituted tetrahydrofurans appear in a large variety of bioactive structures of both natural and unnatural origin. The stereochemistry of the substituents has a profound effect on function; therefore, the development of new methodology for the stereoselective construction of tetrahydrofuran rings is very attractive. A tandem methodology for the stereoselective synthesis of 2,3,5-trisubstitutedtetrahydrofurans is reported here. This involves a catalytic C-H insertion of diazocarbonyl acetal templates followed by the stereoselective reductive cleavage of the resultant bicyclic acetals. A key area of this project is the formation and reaction of diazoketones. The diazoketones were prepared in good yields (70-85%) by acylation of diazomethane with a mixed anhydride, which involves the initial activation of the acid group of the corresponding acid acetal precursors. Alternatives to the use of diazomethane have been examined but proved to be less efficient. Two routes towards the synthesis of the acid acetals have been examined. A one-pot process involving the treatment of 1,3- and 2,2-disubstitutedpropane- 1,3-diols with pyruvic acid gave poor yields (30-38%). A two-step procedure involving the initial synthesis of pyruvate ester acetals, by ketalisation of 2-substitutedpropane- 1,3-diols followed by their hydrolysis, led to the formation of acid acetals in good yield (~ 75% after 2 steps). Rhodium (II) acetate is an efficient catalyst for the decomposition of diazoketones leading to transition metal-carbenoids (or metallocarbenes), reactive intermediates susceptible to insertion into a C-H bond. Determination of the optimum conditions for the C-H insertion process has been achieved and electronic effects of the substituents on the C-H insertion process have been examined. The reaction was regioselective, occurring at the C-H bond a to the oxygen, and a variety of bicyclic ketones were prepared in moderate but reproducible yields. The bicyclic core intermediate, present in naturally occurring bioactive molecules, is also a target for synthesis. An attempt to synthesize sordidin, an aggregation pheromone released by male banana weevils, is reported. Finally, the reductive cleavage of these bicyclic ketones, upon Et3SiH/Lewis Acid treatment, has been examined. In all cases, the reactions were stereoselective leading to 2,3-anti-3,5-cis-trisubstituted tetrahydrofurans. The stereoselectivity increased with the size of the OR group at C-3.

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A number of complexes of substituted phenolate ions with divalent metals have been prepared. These are of the form M(OR)2(L)2, where M = Co(Il), Ni(II) or Cu(ll); OR = 4-formyl-2-methoxyphenolate, 2-ethxy-4-formylphenolate, 2-methoxy-4-nitrophenolate, 2-methyl-4-nitrophenolate, 2,4,6-trichIorophenolate or pentachlorophenolate; L = water, pyridine, ammonia or -1/2 N,N,N,N-tetramethylethylenediamine. Some compounds possess additional molecules of water. An attempt has been made to establish the stereochemistry of the copper(II) complexes using their solid state electronic spectra, most of which fall into one of three categories, by comparison to compounds of known structure. The crystal and molecular structure of two copper complexes, namely bis(2-methoxy-4-nitrophenolato)bis(pyridine)copper(II) and Bis(4-formyl-2-methoxyphenoleto)bis(pyridine)copper(II) monohydrate, have been determined by single crystal X-ray methods. The copper(II) ion has a distorted six co-ordinate environment in both complexes, which are monomeric with the phenolate ions bidentate and chelating through the phenolic- and methoxy-oxygens. The solid state electronic spectra of the cobalt(II) and nickel(II) complexes are consistent with six co-ordination about the metal . ion. However, whereas those of the nickel(II) complexes are-typical of regular octahedral species, the cobalt(II) spectra suggest that considerable distortion from regular octahedral stereochemistry is present. Probable structures are proposed for all the complexes, although in some cases there are several possibilities. These arise either because some compounds contain additional molecules of water, the bonding role of which is uncertain, or, in the case of copper(II), the metal ion stereochemistry is in doubt. The behaviour of the three divalent metal ions with these ligands is compared and contrasted where appropriate.