David I. Davies

Alkanes and Alkenes

In 1849 [1] Kolbe attempted to isolate the methyl radical via the electrolysis of an aqueous solution of potassium acetate. The hydrocarbon he obtained is now known to be ethane, but further investigations into the electrolysis of the alkali metal salts of aliphatic carboxylic acids have shown the reaction to have considerable utility for the synthesis of dimeric hydrocarbon products.

Synthesis from arachidonic acid of potential prostaglandin precursors

Arachidonic acid has been converted by aerobic oxidation with lipoxygenase (ex soybean) as catalyst and in the presence of sodium borohydride in a one-pot procedure (1 g scale) into (5Z,8Z,11Z,13E)(15S)-15-hydroxyeicosa-5,8,11,13-tetraenoic acid. The methyl (15S)-15-hydroxyeicosatetraenoate or its p-nitrobenzoate derivative may be epoxidised with m-chloroperbenzoic acid to afford mixtures of the 5,6-, 8,9-, 11,12-, and 13,14-monoepoxides together with a mixture of bisepoxides. The methyl (15S)-15-(p-nitrobenzoyloxy)eicosatetraenoate epoxides can be separated by preparative t.l.c. The methyl (15S)-15-(mercaptoacetoxy)eicosatetraenoate has been prepared from the chloroacetate derivative of the methyl (15S)-15-hydroxyeicosatetraenoate by reaction with potassium thioacetate followed by selective hydrolysis of the thioester function.

The structure of glutaconic anhydride and the synthetic utility of its Diels–Alder adduct with cyclopentadiene

In non-polar solvents glutaconic anhydride exists predominantly as its dioxo-tautomer (1). Diels–Alder reaction with cyclopentadiene affords 3-endo-carboxynorborn-5-en-2-endo-ylacetic acid anhydride (5) having considerable synthetic potential, and which on hydrolysis gives the corresponding bis-endo-dicarboxylic acid (6a). The dimethyl ester of (6a) may be epimerised and hydrolysed to the trans-dicarboxylic acid, 3-exo-carboxynorborn-5-en-2-endo-ylacetic acid (9a). The acids (6a) and (9a) have been characterised as a γ-iodolactone (7a) and a δ-iodolactone (13), respectively.

Carboxylic Acids and Their Derivatives

Radical additions to unsaturated compounds are attractive methods for preparing carboxylic acids and their derivatives (ester, halide, lactone, amide, anhydride). The carboxylic acid function may be in the unsaturated compound, for example cyclopentanone adds to undecylenic acid affording a 70% yield of product [1].

Free Radical Reactions

In recent years many different reactions have been found to involve the intermediacy of free radicals. Such reactions, although diverse in nature, do have a number of common features. In a first stage radicals are usually produced by the thermal or photochemical fission of a covalent bond, or in a redox reaction. Less usual is radical formation by molecule-molecule interaction. In a second stage radicals may combine or disproportionate to give products, substitute for an atom or group in a neutral molecule, add to multiple bonds, fragment or rearrange. When, in successive stages a radical reacts with a substrate to produce a new radical, and this new radical reacts with the original radical source to afford a product, so regenerating the original radical, a chain reaction is set up. This continues until the chain is terminated by radicals being removed from the system. As an alternative to reaction with a substrate, free radicals can also afford products in oxidative processes. Because of the diversity of reaction that a radical may undergo, a number of different products usually results from a reaction involving free radicals. Due to the increase in knowledge of radical reactions (Organic Reaction Mechanisms covering the year 1975 surveys 1,100 papers on radical reactions [1]), and of how they are affected by change in reaction conditions, certain reactions have been developed to give one readily isolated product. Such reactions can often be useful in affording products that are not readily available by other means.

Reactions of cyclo-octatetraene and its derivatives. Part V. Addition of bromotrichloromethane, carbon tetrachloride, and thiophenol to tricyclo[4.2.2.02,5]deca-3,7-diene-9,10-dicarboxylic anhydride

The free radical addition of bromotrichloromethane and carbon tetrachloride to tricyclo[4.2.2.02,5]deca-3,7-diene-9,10-dicarboxylic anhydride (I) results in trans-addition to the cyclobutene double bond. The structures (VIa) and (VIb) proposed for the products are based on n.m.r. studies of the adducts and various related compounds; by analogy structure (VIc) is suggested for the thiophenol adduct.

Acid-catalysed lactonisation and iodolactonisation of norbornene-carboxylic acids

The acid-catalysed lactonisation of 3-(norborn-5-en-2-yl)propionic acid and 4-(norborn-5-en-2-yl)butyric acid affords 3-(2-exo-hydroxynorborn-2-endo-yl)propionic acid spiro-γ-lactone and 4-(2-exo-hydroxynorborn-2-endo-yl)butyric acid spiro-δ-lactone, respectively. The corresponding spiro-iodo-δ-lactone is obtained on iodolactonisation of 4-(norborn-5-en-2-yl)butyric acid. These results, coupled with known results on lactonisation of other carboxylic acid derivatives of norbornene, point to common reaction pathways with a series of equilibrating norbornyl-type cations involved in product formation. Results with 3-exo-carboxy- and 3-exo-methylnorborn-5-en-2-endo-yl-carboxylic acids indicate that the relative importance of various intermediates in determining product formation is affected by the presence of substituents.

An approach to the synthesis of cyclopentane analogues of the lyxosyl C-nucleosides

The Diels–Alder adduct of cyclopentadiene and maleic anhydride has been converted into 5-endo,6-endo-O-isopropylidene-3-methoxycarbonylnorborn-2-ene. Cleavage of the double bond in this unsaturated ester affords methyl 2-(2′β,3′β-O-isopropylidene-4′β-methoxycarbonylcyclopent-1′β-yl)glyoxalate in which all the substituents are on the same side of the cyclopentane ring. This cyclopentane derivative is a potential synthon for cyclopentane analogues of the lyxosyl C-nucleosides, and its transformation into 5-(4′β-hydroxymethyl-2′β,3′β-dihydroxycyclopent-1′β-yl)-6-azauracil has been examined.

The synthesis of the 9,11-hydroxyethano-prostaglandin endoperoxide H2 analogue

The 9,11-hydroxyethano-prostaglandin endoperoxide H2 analogue (4a) and its methyl ester (4b) have been prepared in 4.3 and 10% yield respectively from the readily prepared 3-exo-methoxycarbonyl-6-endo-hydroxy-5-exo-iodonorborn-2-endo-ylacetic acid δ-lactone (5).

Product formation and identification in the reaction of 6-endo-hydroxy-5-exo-iodo-3-exo-phenylnorborn-2-endo-ylcarboxylic acid γ-lactone with silver toluene-p-sulphonate

The reaction of 6-endo-hydroxy-5-exo-iodonorborn-2-endo-ylcarboxylic acid γ-lactone with silver toluene-p-suiphonate affords 7-syn-hydroxy-3-exo-tosyloxynorborn-6-exo-ylcarboxylic acid γ-lactone as the sole product. A comparable reaction with 6-endo-hydroxy-5-exo-iodo-3-exo-phenylnorborn-2-endo-ylcarboxylic acid γ-lactone affords a mixture of 6-endo-hydroxy-3-exo-phenyl-5-exo-tosyloxynorborn-2-endo-ylcarboxylic acid γ-lactone, 7-syn-hydroxy-5-endo-phenyl-3-exo-tosyloxynorborn-6-exo-ylcarboxylic acid γ-lactone, and 2-exo-hydroxy-4-phenylnorborn-5-en-7-anti-ylcarboxylic acid γ-lactone. Product formation is discussed in terms of possible carbocation intermediates. The latter product is unusual in that the position of the bridgehead C-1 proton in the 1H n.m.r. spectrum is similar to that of the aromatic protons. Product structures were determined by n.m.r. spectroscopic studies, and by chemical conversions.