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Synlett 2004(4): 679-683  
DOI: 10.1055/s-2004-815438
LETTER
© Georg Thieme Verlag Stuttgart · New York

HIV Protease Inhibitor Part 1: Use of Evans’ Oxazolidinone in Intermolecular Diels-Alder Reaction en route to 3,4-Substituted Cyclohexanones

Peter Crackett, Emmanuel Demont*, Andrew Eatherton, Christopher S. Frampton, Jenny Gilbert, Irfan Kahn, Sally Redshaw, William Watson
Roche Discovery Welwyn, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AY, UK
Fax: 44(1438)782088; e-Mail: emmanuel.h.demont@gsk.com;
Further Information

Publication History

Received 12 January 2004
Publication Date:
29 January 2004 (online)

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Abstract

α,β-Unsaturated chiral oxazolidinone 10 can be smoothly obtained from the corresponding aldehyde 14 under Masamune-Roush conditions. Oxazolidinone 10 reacts diastereoselectively with diene 14 under lewis acid catalysis which allows the synthesis of 3,4-substituted cyclohexanone 16 and its derivatives 20, 21, and 22 in good overall yields from ester 4. These compounds can be converted to the corresponding hydroxyethylamine derivatives, analogues of Saquinavir 1, which are known to have antiviral activity.

Key words

oxazolidinone - Diels-Alder - cyclohexanone - cyclohexane - HIV protease inhibitor

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1

Present address: GlaxoSmithKline. The Frythe, Welwyn, AL6 9AR Hertfordshire, UK.

17

CCDC No. 217034 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html [or from the CCDC 12 Union Road Cambridge CB2 1EZ UK; fax: +44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].