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Synlett 2010(4): 579-582  
DOI: 10.1055/s-0029-1219210
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Novel Asymmetric Azaspirocyclisation Using a Morita-Baylis-Hillman-Type Reaction

Jonathan C. Killena, John Leonardb, Varinder K. Aggarwal*a
a School of Chemistry, University of Bristol, Cantock’s Close, Bristol BS8 1TS, UK
Fax: +44(0)1179298611; e-Mail: v.aggarwal@bristol.ac.uk;
b Process R&D, AstraZeneca plc, Silk Road Business Park, Macclesfield, Cheshire SK10 2NA, UK
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Publication History

Received 3 December 2009
Publication Date:
19 January 2010 (online)

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Abstract

A Morita-Baylis-Hillman-type reaction has been applied to the asymmetric preparation of azaspirocycles in high yield and diastereoselectivity. The optimisation of the reaction is discussed and a model for the origin of diastereoselectivity is proposed.

Key Words

Morita-Baylis-Hillman-type reaction - azaspirocyclisation - spiro compounds - asymmetric synthesis - diastereoselectivity

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11

We were not able to obtain crystals of the 5,5-spirocycle for analysis by X-ray diffraction, and we were unsuccessful in finding NOE correlations to assign its stereochemistry. The spirocentre stereochemistry is therefore not known in this case.