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DOI: 10.1055/s-2007-968760
Asymmetric Organocatalytic Cyclopropanation of Enals
Contributor(s):Benjamin List, Subhas Chandra PanStockholm University, Sweden
A Simple Organocatalytic Enantioselective Cyclopropanation of α,β-Unsaturated Aldehydes
Adv. Synth. Catal. 2007, 349: 1028-1032
Publication History
Publication Date:
24 July 2007 (online)
Key words
cyclopropanation - enals - iminium catalysis - enamine catalysis - enantioselectivity
Significance
A highly chemo- and enantioselective organocatalytic cyclopropanation of α,β-unsaturated aldehydes with bromomalonates and 2-bromo acetoacetate has been developed. Pyrrolidine catalyst 1 in combination with Et3N has been found to be effective for this reaction. The reaction proceeds through both iminium and enamine catalysis. With 20 mol% of catalyst 1, moderate to good yields (50-88%) and high enantioselectivities (er = 97:3 to 99.5:0.5) were obtained for different β -substituted enals. In the case of 2-bromo acetoacetate the products were obtained in 3:1 ratio with high enantioselectivity (er = 97:3).
Comment
MacMillan and co-workers have earlier developed an organocatalytic cyclopropanation reaction between stabilized ylides and enals using 2-carboxylic acid dihydroindole as the catalyst (J. Am. Chem. Soc. 2006, 127, 3240). Ley and co-workers also described an amine-catalyzed nitro cyclopropanation of cyclohexenones (Chem. Commun. 2006, 4836). The method as developed by the authors of the present article is highly useful because of its operational simplicity. The authors have determined the absolute configuration of their reaction product by converting it into a known β-malonate ester via an elegant carbene-catalyzed redox esterification.