Catalytic asymmetric phase-transfer Michael reaction and Mannich-type reaction of glycine Schiff bases with tartrate-derived diammonium salts.
Catalytic asymmetric Michael and Mannich-type reactions of glycine Schiff bases with chiral two-center organocatalysts, tartrate-derived diammonium salts (TaDiASs), are described. On the basis of conformational studies, optimized TaDiASs with a 2,6-disubstituted cyclohexane spiroacetal were newly designed. These TaDiASs catalyzed the asymmetric Michael and Mannich-type reactions of glycine Schiff bases with higher enantioselectivity than previous catalysts. In the Mannich-type reaction, aromatic N-Boc-protected imines (Boc = tert-butoxycarbonyl) as well as enolizable alkyl imines were applicable. As a synthetic application of the catalytic asymmetric Mannich-type reaction with the optimized TaDiASs, we developed a catalytic asymmetric total synthesis of (+)-nemonapride, which is an antipsychotic agent.
Shibuguchi
Tomoyuki
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Mihara
Hisashi
H
Kuramochi
Akiyoshi
A
Ohshima
Takashi
T
Shibasaki
Masakatsu
M
D001549:Benzamides / Q000138:chemical synthesis; D002384:Catalysis; D005998:Glycine / Q000737:chemistry; D008968:Molecular Conformation; D012545:Schiff Bases / Q000737:chemistry*; D013644:Tartrates / Q000737:chemistry*
D001549:Benzamides; D012545:Schiff Bases; D013644:Tartrates; C030265:nemonapride; D005998:Glycine; C029768:tartaric acid