John Kitteringham

Practical methylation of aryl halides by Suzuki–Miyaura coupling

Abstract A number of aryl halides (X=Cl, Br, I) can be converted to the corresponding toluenes in an operationally simple manner using trimethylboroxine (TMB) as a partner for palladium-catalysed Suzuki–Miyaura coupling.

Radical cyclisations of methylenecyclopropyl azetidinones—synthesis of novel tricyclic β-lactams

Addition of lithium bis(methylenecyclopropyl)cuprates to acetoxy azetidinones gives methylenecyclopropyl azetidinones, which can be converted to various radical cyclisation precursors. Attempted 4- exo cyclisation of 3 led only to reduced product, while cyclisation of 5 , using CuCl/bipy, gave a carbacephem, via a 5- exo cyclisation, but in low yield. Cyclisation of 6 and 7 , however, gave novel tricyclic β-lactams, as the result of 7- endo cyclisation, in good yield, and a cyclisation of bromide 23 led to the tricyclic β-lactam 24 , via a radical cascade sequence.

Novel syntheses of camptothecin alkaloids, part 2. concise synthesis of (S)-camptothecins

Abstract A 9-step, convergent total synthesis of ( S )-camptothecin alkaloids is described. The intramolecular [4+2] cycloaddition of an N-arylimidate with an alkyne is used to prepare the alkaloid ABC ring system. 1 The chiral center is derived utilizing Seebachs chemistry 2 for the diastereoselective Michael addition of a chiral dioxolanone enolate to a methylene malonate acceptor. The total synthesis of non-racemic topotecan is accomplished from (S)-10-hydroxycamptothecin in an additional step.

Lewis acid mediated cyclisation of methylenecyclopropyl ketones and aldehydes

Abstract The Lewis acid mediated cyclisation of various methylenecyclopropyl ketones, ketals and aldehydes has been investigated as a new route to six- and seven-membered rings. Cyclisation of aldehyde 6, ketal 9 and ketone 11 with TiCl4 gave cyclohexene products, and cyclisation of ketal 10 gave a dichlorocycloheptene, all via nucleophilic addition of the methylenecyclopropyl π bond to the activated carbonyl. Cyclisation of ketone 12, however, with SnCl4, gave a cyclopentanol 21, presumably via nucleophilic addition of a cyclopropyl σ bond to the activated carbonyl.

1,4 additions with lithium bis(methylenecyclopropyl)cuprate

Addition of lithium bis(methylenecyclopropyl) cuprate to alpha,beta -unsaturated ketones provides an efficient route to methylenecyclopropyl ketones which on treatment with TiCl4 give a range of cyclised products.

Lewis acid mediated cascade reactions of silyl-substituted methylenecyclopropyl ketones

Abstract The Lewis acid mediated cyclisation of various silyl-substituted methylenecyclopropyl ketones has been investigated. The presence of the silyl-substituent enhances the reactivity of the methylene cyclopropane in comparison to our earlier study on non-silyl-substituted methylenecyclopropyl ketones, allowing milder Lewis acids (BF 3 ·Et 2 O or BF 3 ·2AcOH) to be used for the cyclisation reaction. The mild conditions used allow the allyl cation, formed as an intermediate in the cyclisation, to be trapped in further carbon–carbon bond-forming reactions.

USE OF METHYLLITHIUM IN METAL/HALOGEN EXCHANGE; A MILD AND EFFICIENT METHOD FOR THE SYNTHESIS OF ORTHO SUBSTITUTED TOLUENES

Methyllithium, in the presence of excess methyl iodide, can be used to convert suitably substituted aromatic bromides to the corresponding toluenes under mild conditions and in high yield.