Asymmetric synthesis of beta-nitro ketones via Michael addition of lithiated alpha-amino nitriles to nitroalkenes.
Alpha-amino nitriles, easily prepared from aldehydes, KCN, and an enantiopure secondary amine auxiliary, are metalated and used as nucleophiles in asymmetric Michael additions to nitroalkenes to afford the Michael adducts in good yields and good to excellent diastereoselectivities. After chromatographic purification, the diastereomerically pure 1,4-adducts are cleaved under acidic conditions to give the beta-nitro ketones in good yields and with two exceptions in good to excellent enantiomeric excesses (ee = 86-99%). The absolute configuration was determined by X-ray structure analysis.
Enders
Dieter
D
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany. enders@rwth-aachen.de
Förster
Dominik
D
Raabe
Gerhard
G
Bats
Jan W
JW