Enantioselective synthesis of gabapentin analogues via organocatalytic asymmetric Michael addition of α-branched aldehydes to β-nitroacrylates.
Michael addition reaction of α-branched aldehydes to β-nitroacrylates was successfully carried out by using a mixed catalyst consisting of a primary amino acid, L-phenylalanine, and its lithium salt to give β-formyl-β'-nitroesters having a quaternary carbon centre in good yields (up to 85%) with high enantioselectivity (up to 98% ee). By using benzyl β-nitroacrylates as Michael acceptors, the obtained β-formyl-β'-nitroesters were converted into various 4,4-disubstituted pyrrolidine-3-carboxylic acids including analogues of gabapentin (Neurotin(®)) in one step from the Michael adducts in high yields.
Division of Chemical Process Engineering, Faculty of Engineering, Hokkaido University, Kita 13-jo Nishi 8, Sapporo, Hokkaido 060-8628, Japan. myoshida@eng.hokudai.ac.jp
Masanori
M
Yoshida
Erika
E
Masaki
Hiroto
H
Ikehara
Shoji
S
Hara