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Synlett 2010(12): 1775-1778  
DOI: 10.1055/s-0030-1258110
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Expeditious Method for the First Asymmetric Synthesis of Dexoxadrol from the Chiral Pool

Pablo Etayo, Ramón Badorrey, María D. Díaz-de-Villegas*, José A. Gálvez*, Pilar López-Ram-de-Víu
Departamento de Química Orgánica, Instituto de Ciencia de Materiales de Aragón, Instituto Universitario de Catálisis Homogénea, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain
Fax: +34(976)761202; e-Mail: loladiaz@unizar.es; e-Mail: jagl@unizar.es;
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Publication History

Received 19 April 2010
Publication Date:
30 June 2010 (online)

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Abstract

A new, straightforward and high-yielding methodology for the asymmetric synthesis of 2-(1,3-dioxolan-4-yl)piperidines is described. This approach involves a highly stereoselective addition of vinylmagnesium bromide to N-(3-butenyl)imines derived from d-glyceraldehyde diphenyl ketal and a ring-closing metathesis reaction as key steps. This procedure was used for the first asymmetric synthesis of (S)-2-[(S)-2,2-diphenyl-1,3-dioxolan-4-yl]piperidine (dexoxadrol) starting from conveniently protected d-mannitol in six steps in 43% overall yield.

Key words

imines - piperidines - metathesis - ring-closure - stereo­selective synthesis

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1

Present address: Institute of Chemical Research of Catalonia (ICIQ), Avgda. Països Catalans 16, 43007 Tarragona, Spain

12

CCDC 773631 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:+44 (1223)336033