A temporary stereocentre approach for the asymmetric synthesis of chiral cyclopropane-carboxaldehydes

M Cheeseman, Iwan R Davies, Philip Axe, Andrew L Johnson, Steven D Bull

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

A novel way of combining chiral auxiliaries and substrate directable reactions is described that employs a three-step sequence of aldol/cyclopropanation/retro-aldol reactions for the asymmetric synthesis of enantiopure cyclopropane-carboxaldehydes. In the first step, reaction of the boron enolate of (S)-N-propionyl-5,5-dimethyl-oxazolidin-2-one with a series of α,β-unsaturated aldehydes affords their corresponding syn-aldol products in high de. In the second step, directed cyclopropanation of the alkene functionalities of these syn-aldols occurs under the stereodirecting effect of their temporary β-hydroxyl stereocentres to give a series of cyclopropyl-aldols in high de. Finally, retro-aldol cleavage of the lithium alkoxide of these cyclopropyl-aldols results in destruction of their temporary β-hydroxy stereocentres to afford the parent chiral auxiliary and chiral cyclopropane-carboxaldehydes in >95% ee. The potential of this methodology has been demonstrated for the asymmetric synthesis of the cyclopropane containing natural product cascarillic acid in good yield.
Original languageEnglish
Pages (from-to)3537-3548
Number of pages12
JournalOrganic and Biomolecular Chemistry
Volume7
Issue number17
DOIs
Publication statusPublished - 2009

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