John M. Herbert

The scope and limitations of deuteration mediated by Crabtree's catalyst

Abstract Exchange of protons for deuterons mediated by Crabtrees catalyst, 1, is directed efficiently by a functional group containing an sp2-hybridised nitrogen or oxygen atom; more electron-rich substrates are, in general, deuterated more efficiently. The electronic effects of substituents in the arene ring are critical only where the directing group is poor, in which case exchange is generally promoted by electron donating substituents, but the exchange is impeded by bulky meta-substituents.

Conditions for deuterium exchange mediated by iridium complexes formed in situ

Abstract A series of iridium-based complexes formed in situ, containing pyridine, phosphines, triphenylarsine, triphenylstibine, and triphenylamine as ligands, has been screened for ability to mediate ortho-exchange of hydrogen in a series of model substrates. Improved incorporation into a number of substrate classes has been achieved. The electronic properties and number of ligands at the metal centre are instrumental in determining which catalysts are best suited to exchange in any given substrate.

Deuterium exchange mediated by an iridium–phosphine complex formed in situ

Bis(triorganophosphine)(cyclooctadiene)iridium(I) tetrafluoroborates, 2, are readily generated in situ and utilised for the exchange of deuterium into a variety of aromatic substrates. The efficiencies of deuterium exchange using 2 formed in this way are comparable to those observed in exchange processes where the isolated pre-catalysts were used.

Transition metal promoted acetylene isomerisation reactions in organic synthesis: A synthesis of (+)-(4S,5S) —muricatacin

Abstract An acetylene —vinylidene rearrangement has been employed as a key step in the enantiospecific synthesis of (+)-(4S,5S) —muricatacin.

Transition metal promoted acetylene isomerisation reactions in organic synthesis

Abstract A transition metal mediated acetylene-vinylidene rearrangement has been developed for the synthesis of spirocyclic lactones

Carbon-11 labeled radioligands for imaging brain cannabinoid receptors.

Two radioligands, [(11)C] SR149080 and its morpholino analog [(11)C] SR149568, were synthesized by reaction of the respective phenolic precursors with [(11)C] methyl iodide. Both radioligands had appropriate regional brain distribution for cannabinoid receptors in mice with peak target to non-target ratios of 2.2 for [(11)C] SR149080 and 1.6 for [(11)C] SR149568 at 90 and 30 minutes post-injection respectively. The uptake of both tracers was blocked with a 1 mg/kg dose of SR141716A.

Preparation of indole-2-carboxamides by palladium-catalysed carbonylation

Abstract Palladium-mediated carbonylation of a 2-iodoindole in the presence of an amine provides an efficient method for the preparation of indole-2-carboxamides. The process is clean and rapid, and appears to be general where the amine component is sufficiently non-volatile.

ortho-Metalation/chlorination of benzoic acid derivatives: preparation of [benzene-U-13C]-rac-clopidogrel ([benzene-U-13C]-rac-SR25990C)

Directed ortho-lithiation is used to form [benzene-U-13C]-2-chlorobenzaldehyde, the key building block for preparation of labelled racemic Clopidogrel ([benzene-U-13C]-rac-SR25990C). Some practical observations are reported concerning the metalation of some derivatives of benzoic acid. Copyright

Preparation and NMR spectroscopic studies of the glucuronides of Irbesartan

Abstract The preparation of N1- and N2- glucuronides of Irbesartan (SR47436) is described. The regiochemistry of the products was established from NMR spectroscopic studies, and the N2-glucuronide was identical to material obtained from natural sources.

One-Pot Reduction of Carboxylic Acids via O-Acylisoureas

Abstract A simple one-pot reduction of aliphatic carboxylic acids to primary alcohols, by treatment with dicyclohexylcarbodiimide followed by lithium borohydride, is reported. The same methodology applied to aromatic carboxylic acids is shown to give a mixture of the alcohols with N-cyclohexylcarboxamides.