A simple protocol for the synthesis of a piperidine-2,6-dione framework from Baylis-Hillman adducts

Abstract

3-Hydroxy-2-methylenealkanenitriles, the Baylis-Hillman alcohols, derived from various aldehydes and acrylonitrile, have been conveniently transformed into 3-arylidene(or alkylidene)piperidine-2,6-diones in an operationally simple one-pot multi-step process involving Johnson-Claisen (J-C) rearrangement, partial hydrolysis, and cyclization. Rearranged Baylis-Hillman alcohols, (E)-2-hydroxymethyl-3-arylprop-2-enenitriles, have been converted into 4-aryl-3-methylidenepiperidine-2,6-diones in a similar reaction sequence. 4-Aryl-3,5-dimethylidenepiperidine-2,6-dione derivatives have been synthesized from Baylis-Hillman compounds, 3-aryl-4-cyano-2-methoxycarbonylpenta-1,4-dienes, obtained via the Baylis-Hillman reaction of methyl (2Z)-2-(bromomethyl)-3-arylprop-2-enoates with acrylonitrile, in a one-pot process. © 2009 Elsevier Ltd. All rights reserved.