title: A temporary stereocentre approach for the asymmetric synthesis of chiral cyclopropane-carboxaldehydes.
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 alpha,beta-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'beta-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 beta-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.
authors.affiliation: Department of Chemistry, University of Bath, Bath, UK BA2 7AY.
authors.forename: Matt
authors.initials: M
authors.lastname: Cheeseman
authors.forename: Iwan R
authors.initials: IR
authors.lastname: Davies
authors.forename: Phil
authors.initials: P
authors.lastname: Axe
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Johnson
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bull
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis*; D001688:Biological Products / Q000138:chemical synthesis; D002264:Carboxylic Acids; D003521:Cyclopropanes / Q000138:chemical synthesis*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D001688:Biological Products; D002264:Carboxylic Acids; D003521:Cyclopropanes; C116609:3-hydroxybutanal; C030797:cyclopropane