Synlett
DOI: 10.1055/s-0039-1690990
cluster
© Georg Thieme Verlag Stuttgart · New York

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

Mateo M. Salgado
,
,
Carlos T. Nieto
,
David Díez
,
Narciso M. Garrido
We are indebted to European Regional Development Fund (FEDER), Spanish Ministerio de Economía y Competitividad (MINECO) for its support (CTQ 2015-68175-R), Junta de Castilla y León (UIC 21), and the Universidad de Salamanca. A.M.C. thanks European Social Fund (FSE) and USAL for his grant.
Further Information

Publication History

Received: 31 July 2019

Accepted after revision: 05 September 2019

Publication Date:
24 September 2019 (online)


Published as part of the ISySyCat2019 Special Issue

Abstract

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.

Supporting Information

 
  • References and Notes

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