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