L-proline-catalyzed enantioselective one-pot cross-Mannich reaction of aldehydes.
This protocol describes a procedure for the synthesis of syn-beta-amino alpha-substituted aldehydes, versatile intermediates in synthetic organic chemistry, via asymmetric, direct, one-pot, three-component, cross-Mannich reaction of two different aldehydes. The reaction consists of two steps; one is the formation of imine by the reaction of aldehyde and p-anisidine in the presence of Pro, and the second step is the enantioselective addition reaction of enamine generated from the other aldehyde and Pro with the imine generated in the first step. As the aldehyde easily racemizes, gamma-amino alcohol was isolated and characterized after reduction. The yield and diastereo- and enantioselectivities are generally excellent. It will take approximately 26 h to complete the protocol: 0.5 h to set up the reaction, 20.5 h for the reaction and 5 h for the isolation and purification.
Hayashi
Yujiro
Y
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. hayashi@ci.kagu.tus.ac.jp
Urushima
Tatsuya
T
Tsuboi
Wataru
W
Shoji
Mitsuru
M
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000605:Amino Alcohols / Q000737:chemistry / Q000302:isolation & purification*; D000814:Aniline Compounds / Q000737:chemistry; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D008352:Mannich Bases / Q000737:chemistry; D015394:Molecular Structure; D011392:Proline / Q000737:chemistry
D000447:Aldehydes; D000588:Amines; D000605:Amino Alcohols; D000814:Aniline Compounds; D008352:Mannich Bases; C013813:4-anisidine; D011392:Proline