Copper-catalyzed enantioselective synthesis of trans-1-alkyl-2-substituted cyclopropanes via tandem conjugate addition-intramolecular enolate trapping

Tim den Hartog; Alena Rudolph; Beatriz Maciá; Adriaan J Minnaard; Ben L Feringa

doi:10.1021/ja105704m

Copper-catalyzed enantioselective synthesis of trans-1-alkyl-2-substituted cyclopropanes via tandem conjugate addition-intramolecular enolate trapping

J Am Chem Soc. 2010 Oct 20;132(41):14349-51. doi: 10.1021/ja105704m.

Authors

Tim den Hartog¹, Alena Rudolph, Beatriz Maciá, Adriaan J Minnaard, Ben L Feringa

Affiliation

¹ Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.

PMID: 20939614
DOI: 10.1021/ja105704m

Abstract

Cu-TolBINAP-catalyzed conjugate addition of Grignard reagents to 4-chloro-α,β-unsaturated esters, thioesters, and ketones leads to 4-chloro-3-alkyl-substituted thioesters and ketones in up to 84% yield and up to 96% ee upon protonation of the corresponding enolates at low temperature. Tandem conjugate addition-enolate trapping, however, yields trans-1-alkyl-2-substituted cyclopropanes in up to 92% yield and up to 98% ee. The versatility of this reaction is illustrated by the formation of key intermediates for the formal syntheses of cascarillic acid and grenadamide.