Peter W. Sheldrake

An efficient method for the synthesis of substituted TosMIC precursors

Abstract Substituted tosylmethyl isocyanides (TosMICs) are useful reagents for which no general method of preparation is available. We describe here a high-yielding method for the synthesis of substituted tosylmethyl formamides, which are readily converted to the corresponding isocyanides.

Synthesis of 2-substituted 1-benzyl-2,3,4,5-tetrahydro-1-benzazepines by palladium catalysis. Observation of a competitive β-hydride elimination pathway

A synthetic route to 1-benzyl-tetrahydro-1-benzazepine is reported, which also permits access to analogous structures with alkyl and aryl substituents at position-2 of the aliphatic ring. Palladium catalysis is utilized in two of the three steps, constructing the seven-membered rings effectively from 2-bromoiodobenzene. Competitive β-hydride elimination was observed in the attempted carbonue5f8nitrogen bond formation with a sterically bulky substrate (when R=tert-butyl).

Use of iron (III) chloride in the efficient preparation of the alkaloid kreysigine by oxidative coupling

Abstract Reaction of the isoquinoline (1) with iron (III) chloride in dichloromethane followed by reductive treatment with methanol gives kreysigine (4) in 71% yield; (2) gives (4) in lower yield as does treatment with water instead of methanol; (8) is the product of a thallium (III) oxidation.

Studies of enzyme-mediated reactions. Part VII. Stereospecific syntheses of tritium-labelled (2R)- and (2S)-dopamines: stereochemical course of hydroxylation of dopamine by dopamine β-hydroxylase (E.C. 1.14.17.1)

An efficient synthesis has been developed for the preparation in high configurational purity of dopamines (3,4-di-hydroxyphenethylamines) stereospecifically labelled at C-2 with isotopes of hydrogen. By incubating (2R)-, and (2S)-[2-2H1]dopamines with dopamine β-hydroxylase (E.C. 1.14.17.1) it has been shown that the pro-R-hydrogen atom is lost in the formation of noradrenaline; thus the hydroxylation of the benzylic methylene group occurs with retention of configuration.

Stereospecificity in the biosynthesis of papaverine

Abstract The stereochemistry of hydrogen removal from C-3 and C-4 in the aromatization of the heterocyclic ring of papaverine has been determined by incorporation experiments with stereospecifically tritiated norreticulines.

Novel cage compounds from inter- and intra-molecular Diels–Alder reactions of heteroaromatic azadienes and methyl coumalate with cyclo-octa-1,5-diene

1,2,4-Triazines, pyridazines, and α-pyrones activated with electron-withdrawing groups were found to react with cyclo-octa-1,5-diene by intermolecular Diels–Alder addition followed by extrusion of nitrogen or carbon dioxide; the resulting 2-aza-1,3-dienes or 1,3-dienes then undergo intramolecular ring-closure reactions to produce novel cage compounds.

Use of dissolving metals in the partial reduction of pyridines: formation of 2-alkyl-1,2-dihydropyridines

The partial reduction of a series of electron deficient pyridines to give both 1,2- and 2,5-dihydropyridines is described. The factors that lead to formation of such dihydropyridines are discussed and it was found that, generally, the presence of two activating groups on the pyridine nucleus is optimal. A series of 2-alkyl-1,2-dihydropyridines was prepared using either Birch or sodium naphthalenide reducing conditions and some preliminary derivatisation chemistry has been examined. The identity of three relevant nitrogen containing heterocycles was proven by X-ray crystallography.

Unexpected synthesis of a 1H-pyrrolo[2,3-e]-1,2,4-triazine

3,6-Dichloro-5-(2-pyrrolidin-1-ylcyclohept-l-enyl)-1,2,4-triazine was found to undergo a facile thermal intramolecular rearrangement; an X-ray crystal structure determination showed the product to be derived from a novel heterocyclic system, 1H-pyrrolo[2,3-e]-1,2,4-triazine.