Jerome F. Hayes

[2,3]-Sigmatropic rearrangements of didehydropiperidinium ylids

The [2,3]-sigmatropic rearrangements of ammonium ylids derived from 1,2,5,6-tetrahydropyridine have been studied: both rearrangement and elimination processes are observed, with rearrangement favoured when aprotic solvents are used in the reaction. The presence of anion-stabilizing substituents on the nucleophilic carbon atom of the intermediate ylid species involved in the tranformation also engenders rearrangement; when certain aryl substituents or two anion-stabilizing groups are present, elimination is not observed, and electron-donating ylid substituents retard rearrangement whilst enhancing elimination.

A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A

A new synthesis of lotrafiban SB-214857-A is reported. The key steps are the preparation of racemic (4-methyl-3-oxo-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-2-yl)-acetic acid methyl ester from 2-nitrobenzyl alcohol, a resolution using an immobilised lipase enzyme and a palladium-catalysed aminocarbonylation reaction.

A novel synthesis of 2,4,5-triarylimidazoles

Aryl cyanides were reacted with α, α-dilithioarylnitromethanes to form 2,4,5-triarylimidazoles in good yield. An unusual cyclisation - elimination mechanism is proposed for this reaction

Aziridinyl anions from a chiral, nonracemic 2-isopropylidineaziridine: surprisingly diastereoselective alkylation reactions

Lithiation and alkylation of a 2-isopropylidineaziridine bearing an (S)-alpha-methylbenzyl group on nitrogen proceeds with high levels of diastereocontrol (80-90% de).

Factors affecting the [3,2]-sigmatropic rearrangements of didehydropiperidinium ylids

The [3,2] sigmatropic rearrangements of cyclic ammonium ylides have been studied with a view to optimizing rearrangement at the expense of elimination

A novel and efficient synthesis of a tetra-substituted imidazole

Abstract A novel synthesis of a tetra-substituted imidazole is described. A key feature of the synthesis is the regioselective deprotonation of picolylpyrrolidinone 3 and the efficient reaction of this anion with an aryl nitrile to give the pyrrolidinoimidazole nucleus in a single step.

A Fluorous-Tagged “Safety Catch” Linker for Preparing Heterocycles by Ring-Closing Metathesis

A fluorous-tagged “safety catch” linker is described for the synthesis of heterocycles with use of ring-closing metathesis. The linker facilitiates the purification of metathesis substrates, the removal of the catalyst, the functionalization of the products, and the release of only metathesis products. The synthesis of a range of heterocycles is described.

Asymmetric synthesis of 2-substituted piperidines using a multi-component coupling reaction: rapid assembly of (S)-coniine from (S)-1-(1-phenylethyl)-2-methyleneaziridine

(S)-Coniine is made using a reaction which assembles the piperidine ring by the sequential formation of four new chemical bonds and installs the C-2 stereogenic centre with high levels of diastereocontrol (90% de).

Generation of metalloenamines by carbon–carbon bond formation: ring opening reactions of 2-methyleneaziridines with organometallic reagents

Ring opening of 2-methyleneaziridines with Grignard reagents in the presence of CuI yields metalloenamines in a regiospecific fashion which can be further reacted with electrophiles to produce functionalised ketones via a one-pot process.

A NOVEL SYNTHESIS OF A 1,3-DISUBSTITUTED 1,3-DIHYDRO-2H-IMIDAZO[4,5-b]PYRIDIN-2-ONE. APPLICATION TO GW808990 A CRF1 RECEPTOR ANTAGONIST

A novel synthesis of a 1,3-disubstituted 1,3-dihydro-2H-imidazo-[4,5-b]pyridin-2-one has been achieved by condensation of iminohydantoin 3 with t-butyl acetoacetate in diglyme at 160 °C. Hydrogenation of the product in the presence of 4-heptanone followed by a Buchwald-Hartwig amination afforded GW808990, a CRF 1 receptor antagonist.