Basil J. Wakefield

Reactions of β-(lithiomethyl)azines with nitriles as a route to pyrrolo-pyridines, -quinolines, -pyrazines, -quinoxalines and -pyrimidines

Abstract Deprotonation of 3-methylazines, followed by reaction with benzonitile, gives an intermediate which, on treatment with additional strong base, cyclises to give 2-phenyl[1H]-pyrrolo[2,3-b]pyridine. The application of this type of reaction to a variety of nitriles and β-methylazines (pyridines, quinolines, pyridines, quinoxalines and pyrimidines) is described.

X-ray crystallographic studies and comparative reactivity studies of a sodium diisopropylamide (NDA) complex and related hindered amides

Two related sodium amide complexes derived from secondary amines with bulky organic substituents have been synthesised and crystallographically characterised. Both [(Pr-i)(2)NNa(TMEDA)](2) and [Cy(Pr-i)NNa(TMEDA)](2) adopt dimeric crystal structures with a central, planar (nitrogen-metal)(2) azametallocycle, a now familiar feature in both lithium amide and sodium amide chemistry. TMEDA ligands chelate in their usual bidentate manner making the Na+ cations four-coordinate with a distorted tetrahedral geometry. In the latter complex, the amido substituents are disposed in a trans conformation with respect to the (NNa)(2) ring plane. The deprotonating ability of the former complex has been tested against that of the parent amide [(Pr-i)(2)NNa](infinity) and the lithium congener [(Pr-i)(2)NLi](infinity) (LDA) in a series of simple organic reactions: selective enolate formation from 2-octanone and 2-methylcyclohexanone; synthesis of diphenylacetic acid via diphenylmethane. In general, the performance of the sodium reagents compares favourably with that of the lithium reagent.

Do the compounds PhCH2Y give geminal dianions on addition of two equivalents of strong base

Abstract Examples of the title reaction are shown not to yield geminal dianions as believed but rather monoanions complexed with a second molecule of the base.

Reduction of bicyclo[3.2.0] hept-2-en-6-one and 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one using dehydrogenase enzymes and the fungus mortierella ramanniana

Bicyclo[3.2.0]hept-2-en-6-one (1) was reduced with an alcohol dehydrogenase from Thermoanaerobium brockii and a whole cell system (M. ramanniana) with excellent substrate enantioselectivity: 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one (2) was similarly reduced using the 3α,20β-hydroxysteroid dehydrogenase from Streptomyces hydrogenans while M. ramanniana furnished both 6S-alcohols (4a), (6b) with high optical purity.

Polychloroaromatic compounds II. Tetrachloropyridyl derivatives of lithium, magnesium and mercury☆☆☆

Abstract Solutions of tetrachloroyridyllithium compounds have been made by the reaction of n-butyllithium with pentachloropyridine; in hydrocarbon solvents, 3,4,5,6-tetrachloro-2-pyridyllithium was the predominant isomer, whereas in diethyl ether,2,3,5,6-tetrachloro-4-pyridyllithium was the major product, 2,3,5,6-Tetrachloro-4-pyridylmagnesium chloride was prepared from pentachloropyridine and magnesium. Bis(2,3,5,6-tetrachloro-4-pyridyl)mercury and 2,3,5,6-tetrachloro-4-pyridylmercuric chloride were made by the reaction of the 4-pyridyllithium compound with mercuric chloride. The 2,3,5,6-tetrachloro-4-pyridylmercuric chloride was isolated as a complex with 2,2′-bipyridine.

Abnormal Nucleophilic Substitution in 3-Trichloromethylpyridine, its N-Oxide and 3,5-Bis(trichloromethyl)pyridine

Abstract The scope of abnormal reactions of nucleophiles with β-trichloromethylazines is further explored: reactions of 3-trichloromethylpyridine with nucleophiles other than methoxide, and reactions of 3-trichloromethylpyridine N-oxide and 3,5-bis(trichloromethyl)pyridine with methoxide. Attack at a ring carbon, followed by hydrogen migration to the side-chain, occurred in most cases, though attack at the trichloromethyl carbon was also sometimes observed. We now report further studies on this type of interesting, and potentially useful, reaction. These involved reactions of 3-trichloromethylpyridine (1) with nucleophiles other than methoxide, comparative reactios of 3-trichloromethylpyridine-N-oxide (4), and reactions of 3,5-bis(trichloromethyl)pyridine (5) with methoxide.

Polyhalogenoaromatic compounds : XXIX. Hexachloro-5,5′-dilithio-4,4′-bipyridine as an intermediate for organometallic and organic syntheses☆

Abstract Metal—halogen exchange between octachloro-4,4′-bipyridine and two molar equivalents of n-butyllithium gives hexachloro-5,5′-dilithio-4,4′-bipyridine. On reaction with dichlorodiphenylsilane or di-π-cyclopentadienyltitanium dichloride, the dilithio compound gives products lacking a metallocyclic ring. With sulphur dichloride the expected thienodipyridine is obtained. The stereochemical features of the reactions and of the products are discussed. Thermolysis of the dilithio compound failed to yield a cyclobutadipyridine. 2,3,6-Trichloropyridine is metallated by n-butyllithium in the 4-position.

Resolution of 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one using Mortierella ramanniana and 3α,20β-hydroxy-steroid dehydrogenase, photochemistry of 3-hydroxy-7,7-dimethylbicyclo[3.2.0]heptan-6-ones, and the synthesis of (+)-eldanolide

The fungus Mortierella ramanniana reduced 7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one (1) to give the (6S)-endo-alcohol (9) and the (6S)-exo-alcohol (10). In contrast the enzyme 3α,20β-hydroxy-steroid dehydrogenase was found to give the (6S)-endo-alcohol (9) and recovered optically active ketone. Both processes produced the alcohol (9) in high optical purity. The (6S)-endo-alcohol (9) was converted into the lactone (+)-(4) a late stage synthon for the pheromone eldanolide (+)-(11).

Organometallic derivatives : VII. The lithiation of (ferrocenylmethyl)diphenylphosphine oxide and sulphide☆

Abstract (Ferrocenylmethyl)diphenylphosphine oxide and sulphide have been lithiated with n-butyllithium under mild conditions. Metallation occurred on the α-carbon atom with both the oxide and the sulphide, and condensation of the lithiated intermediates with electrophiles gave a series of α-substituted ferrocenylmethylphosphines.

Tele Nucleophilic Aromatic Substitutions in 1-Nitro-3- and 1,3-Dinitro-5-trichloromethylbenzene, and 3-Trichloromethylbenzonitrile. A New Synthesis of the 1,4-Benzothiazine-3(4H)-one Ring System from 3-Nitrobenzoic Acid

Abstract 3-Trichloromethylnitrobenzene 2 , 1,3-dinitro-5-trichloromethylbenzene 13 and 3-trichloromethylbenzonitrile 18 react with sodium methoxide to give 4-methoxy-3-nitrobenzaldehyde 6 , 4-methoxy-3,5-dinitrobenzaldehyde 15 and 5-dimethoxymethyl-2-methoxybenzonitrile 19 , respectively. Compounds 2 and 13 react with methyl thioglycolate to afford dichloromethylacetates 7 and 16 , respectively. These products are the result of tele nucleophilic aromatic substitution. Compound 18 reacted with methyl thioglycolate to give acetate 20 resulting from nucleophilic displacement of cyanide. Reductive cyclisation of 7 afforded benzothiazine 11 .