Asymmetric Synthesis of 2,3,6-Trisubstituted Piperidines via Baylis –Hillman Adducts and Lithium Amide through Domino Reaction

Synlett DOI: 10.1055/s-0039-1690990 A convenient asymmetric synthesis of methyl (2S,3S,6R)-6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-piperidine-3-carboxylate is described, starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain groups allows an effective cyclization leading to biologically interesting polysubstituted piperidines in which the 2,6-aryl groups could be attached sequentially. [...] © Georg Thieme Verlag Stuttgart · New YorkArticle in Thieme eJournals: Table of contents  |  Abstract  |  Full text

Source: Synlett - September 23, 2019 Category: Chemistry Authors: Salgado, Mateo M. Manchado, Alejandro Nieto, Carlos T. D íez, David Garrido, Narciso M. Tags: cluster Source Type: research