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

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.

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

References and Notes

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

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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 [e-mail], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax:[phone]

13 Hardie WR, Creek W, and Halverstad IF. inventors; PCT Int. Appl. US  3262938.  ; Chem. Abstr. 1996, 65, 12207d