Catalytic enantioselective conjugate addition of cyanide to alpha,beta-unsaturated N-acylpyrroles.
A catalytic enantioselective conjugate addition of cyanide to alpha,beta-unsaturated N-acylpyrroles was developed using the chiral gadolinium catalyst generated from Gd(OiPr)3 and d-glucose-derived ligand 2. Generally high enantioselectivity was obtained from a wide range of substrates; substrates with beta-aryl and beta-vinyl substituents and alpha,beta-disubstituted substrates can now be used. Using this reaction as a key step, short-step syntheses of several pharmaceuticals and their lead compounds were achieved, including the beta-phenyl-substituted GABA analogue and pregabalin.
Mita
Tsuyoshi
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.
Sasaki
Kazuki
K
Kanai
Motomu
M
Shibasaki
Masakatsu
M
D002384:Catalysis; D002934:Cinnamates / Q000737:chemistry; D003486:Cyanides / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D000069583:Pregabalin; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis
D002934:Cinnamates; D003486:Cyanides; D009942:Organometallic Compounds; D011758:Pyrroles; C029010:cinnamic acid; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D005682:Gadolinium