Enantioselective copper-catalyzed cyclopropanation of styrene by means of chiral bispidine ligands

Enantiopure C1- and C2-symmetric bispidine ligands have been synthesized and screened in the asymmetric copper-catalyzed cyclopropanation of styrene. In order to improve the enantiomeric excesses (ee) of the cyclopropane derivatives, the best performing C1-symmetric diamine ligand was selected for studies on the reaction conditions. The optimized procedure allowed us to obtain up to 91% ee for the cis-cyclopropane derivative and up to 79% ee for the trans one.

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(1′R,1R,5S)-3-Methyl-7-(1′-naphthalen-1-yl-ethyl)-3,7- diaza-bicyclo[3.3.1]nonan-9-oneC20H24N2O[α]D20=-30.6 (c 1, CHCl3)Source of asymmetry: (R)-1-naphthalen-1-yl-ethylamineAbsolute configuration: (1′R,1R,5S)

3,7-Bis-((R)-1′-phenyl-ethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-oneC23H28N2O[α]D20=+4.2 (c 0.5, CHCl3)Source of asymmetry: (R)-1-phenyl-ethylamineAbsolute configuration: (R,R)

1,5-Diphenyl-3,7-bis-((R)-1′-phenyl-ethyl)-3,7-diaza-bicyclo[3.3.1]nonan-9-oneC35H36N2O[α]D20=-8.4 (c 1, CHCl3)Source of asymmetry: (R)-1-phenyl-ethylamineAbsolute configuration: (R,R)