Cascade oxime formation, cyclization to a nitrone, and intermolecular dipolar cycloaddition.
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.
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Rachel C
RC
Furnival
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Rungroj
R
Saruengkhanphasit
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Heather E
HE
Holberry
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Jonathan R
http://orcid.org/0000-0003-3076-870X
JR
Shewring
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Hélène D S
HD
Guerrand
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Harry
H
Adams
Department of Chemistry, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK. i.coldham@sheffield.ac.uk.
Iain
http://orcid.org/0000-0003-4602-6292
I
Coldham
D000475:Alkenes / Q000737:chemistry; D003500:Cyclization; D061565:Cycloaddition Reaction; D009589:Nitrogen Oxides / Q000737:chemistry*; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry*
D000475:Alkenes; D009589:Nitrogen Oxides; D010091:Oximes; C015388:nitrones