Pipecolic acid-catalyzed direct asymmetric mannich reactions.
Mannich reactions between aldehydes and N-p-methoxyphenyl-protected alpha-imino ethyl glyoxylate have been performed using (S)-pipecolic acid as catalyst. The reactions give both syn- and anti-products (dr=1.4-2:1) with high enantioselectivities (>98% ee). In contrast, (S)-proline-catalyzed reactions give mainly syn-products with high enantioselectivities. Computational studies reveal that the energetic preference between the transition structures involving the s-cis-enamine and the s-trans-enamine is smaller for the pipecolic acid as compared to proline, yielding the (2S,3R)-anti and the (2S,3S)-syn Mannich product in nearly equal amounts.
Cheong
Paul Ha-Yeon
PH
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095-1569, USA.
Zhang
Haile
H
Thayumanavan
Rajee
R
Tanaka
Fujie
F
Houk
K N
KN
Barbas
Carlos F
CF
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D006038:Glyoxylates / Q000737:chemistry*; D015394:Molecular Structure; D010875:Pipecolic Acids / Q000737:chemistry*; D011392:Proline / Q000737:chemistry; D013237:Stereoisomerism; D013816:Thermodynamics
D000447:Aldehydes; D006038:Glyoxylates; D010875:Pipecolic Acids; D011392:Proline; C031345:pipecolic acid