Kenneth E. Walsh

Homoallyl-substituted vinylcyclopropanes from alpha,beta-unsaturated ketones and allylindium derivatives

Simply reversing the order of addition of aqueous acid and Et2 O to the Barbier intermediate 1 of the known indium-mediated allylation leads to unprecedented deoxygenative rearrangements [Eq. (a)].

Regioselectivity and diastereoselectivity in the indium-mediated homoallyl-cyclopropanation of dibenzylidene acetone (dba)

Abstract Indium mediated reaction of dibenzylidene acetone (dba) with [ 2 H 2 ]-allyl bromide affords 1,1-distyryl-2-(but-3-enyl) cyclopropane 7 (a triene) as a mixture of four isotopomers. Whilst this reaction is not regiospecific, the analogous reaction employing crotyl bromide in place of allyl bromide is highly regioselective and somewhat selective for the cis cyclopropane isomer. When the reaction is performed with dimethylallyl bromide, cyclopropanation fails and tetraene products are obtained instead.

Highly Substituted Homoallylvinylcyclopropanes by Indium‐Mediated Reaction of α,β‐Unsaturated Ketones and Aldehydes with Allylic Halides

Allylindium reagents, prepared from excess allylic halide (Br or I) and indium metal, react with α,β-unsaturated ketones and aldehydes to give, after aerobic acidic workup, homoallyl-substituted vinylcyclopropanes. This process was explored and developed after a chance discovery arising from a side reaction in an attempted Pd-catalysed process. The structure of the cyclopropane arising from the reaction of bis(p-chlorobenzylidine)acetone was confirmed by X-ray crystallography. Whilst bis-α,β−unsaturated ketones give rise to a single homoallylcyclopropane species, α,β-unsaturated ketones and aldehydes give diastereomeric mixtures whose relative stereochemistry were assigned by NOE experiments. Crotylindium reagents react with good to perfect regioselectivity to afford tetrasubstituted cyclopropanes but prenylindium reagents fail to generate the analogous pentasubstituted rings.

The azomethine ylide strategy for β-lactam synthesis. A comprehensive mechanistic evaluation

The release of azomethine ylide reactivity from oxazolidinones such as 4a/4b and 7 is proposed to involve a stepwise fragmentation via12 and 13 followed by cycloaddition (to an alkene) leading to adduct 14, which then undergoes decarboxylation under the reaction conditions to give the observed product 15. In the case of CC-based dipolarophiles, the cycloaddition is concerted and stereospecific, and the cycloaddition step is rate determining. Extensive experimental, together with computational data, including racemisation and kinetic studies, as well as the changes in reactivity associated with varying key structural features associated with the β-lactam based oxazolidinones is presented in support of the favoured mechanistic postulate. The fragmentation–cycloaddition–decarboxylation sequence is an alternative pathway for the release of an azomethine ylide from an oxazolidinone to that process already well established for N-alkyl oxazolidinones (concerted decarboxylation before cycloaddition). The N-acyl component associated with 4 may influence this change in mechanism, but specific structural features associated with the β-lactam system (ring strain and the presence of a malonyl moiety) are most likely responsible for the mechanistic divergence that is observed.

Aldehydes and ketones as dipolarophiles: application to the synthesis of oxapenams

2-Substituted (6a–e) and 2, 2-disubstituted oxapenams (6f–g) are obtained in one step by thermolysis of the β-lactam-based oxazolidinone 4 in the presence of aldehydes and reactive ketones respectively; the C(6)-substituted oxazolidinone variant 7 reacts with hexafluoroacetone to give the enantiomerically pure oxapenam 8.