Aliphatic ketones containing a chloride and alkene were heated with hydroxylamine to promote cascade, tandem condensation to oximes, cyclization to nitrones, and 1,3-dipolar cycloaddition to tricyclic isoxazolidines as single stereoisomers. Single regioisomers were obtained when three atoms linked the ketone and dipolarophile to give five-membered rings but mixtures resulted with four atoms in the tether unless a terminal ester was located on the alkene. The N-O bond in the products could be reduced to give spirocyclic amines and diamines.

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Simple haloaldehydes, including enolisable aldehydes, were found to be suitable for the formation of cyclic products by cascade (domino) condensation, cyclisation, dipolar cycloaddition chemistry. This multi-component reaction approach to heterocyclic compounds was explored by using hydroxylamine, a selection of aldehydes, and a selection of activated dipolarophiles. Initial condensation gives intermediate oximes that undergo cyclisation with displacement of halide to give intermediate nitrones; these nitrones undergo in situ intermolecular dipolar cycloaddition reactions to give isoxazolidines. The cycloadducts from using dimethyl fumarate were treated with zinc/acetic acid to give lactam products and this provides an easy way to prepare pyrrolizinones, indolizinones, and pyrrolo[2,1-a]isoquinolinones. The chemistry is illustrated with a very short synthesis of the pyrrolizidine alkaloid macronecine and a formal synthesis of petasinecine. Scheme 1 Previous studies with related aldehydes. 4,6 † Electronic supplementary information (ESI) available. CCDC 1006037-1006042,

A direct C–H functionalization approach to access C3-alkylated 2-pyridone derivatives is reported. This study utilizes N-hydroxyphthalimide (NHPI) esters of various carboxylic acids as sources for alkyl radicals by reductive cleavage...

An efficient synthetic approach to the core structure of the manzamine alkaloids is reported, particularly in relation to incorporating a one-carbon unit in ring B from which the aldehyde in ircinal A or the betacarboline unit in manzamine A could potentially be generated. The key steps involve a JohnsonÐClaisen rearrangement, enolate alkylation, dithiane alkylation and a stereoselective intramolecular dipolar cycloaddition of an azomethine ylide, which provided the desired tricyclic ABC core structure.