The N-chloroformylimidazolidinone derivative of enantiopure l-alanine was deprotonated to form an enolate and functionalized with a series of allylic halides. Treatment of the resulting carbamoyl chlorides with potassium iodide led to cyclization of the allylic substituent onto the carbonyl group in an intramolecular aliphatic Friedel–Crafts-type acylation that corresponds to an aliphatic Bischler–Napieralski reaction. The product 3,4-dihydropyridinones were amenable to further functionalization, and finally hydrolysis, to deliver a series of enantio-enriched pipecolic acid derivatives.
Bibliographical noteProvisional acceptance date added, based on publication information.
Amer, M. M., Olaizola, O., Carter, J., Abas, H., & Clayden, J. (2020). An Aliphatic Bischler–Napieralski Reaction: Dihydropyridones by Cyclocarbonylation of 3-Allylimidazolidin-4-ones. Organic Letters, 253-256. https://doi.org/10.1021/acs.orglett.9b04250