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The Direct Catalytic Asymmetric Cross‐Mannich Reaction: A Highly Enantioselective Route to 3‐Amino Alcohols and α‐Amino Acid Derivatives
Author(s) -
Córdova Armando
Publication year - 2004
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305646
Subject(s) - mannich reaction , chemistry , enantioselective synthesis , catalysis , amine gas treating , organic chemistry , amino acid , yield (engineering) , proline , enantiomer , biochemistry , materials science , metallurgy
The first proline‐catalyzed direct catalytic asymmetric one‐pot, three‐component cross‐Mannich reaction has been developed. The highly chemoselective reactions between two different unmodified aldehydes and one aromatic amine are new routes to 3‐amino aldehydes with dr >19:1 and up to >99 % ee . The asymmetric cross‐Mannich reactions are highly syn ‐selective and in several cases the two new carbon centers are formed with absolute stereocontrol. The reaction does not display nonlinear effects and therefore only one proline molecule is involved in the transition state. The reaction was also catalyzed with good selectivity by other proline derivatives. The Mannich products were converted into 3‐amino alcohols and 2‐aminobutane‐1,4‐diols with up to >99 % ee . The first one‐pot, three‐component, direct catalytic asymmetric cross‐Mannich reactions between unmodified aldehydes, p ‐anisidine, and ethyl glyoxylate have been developed. The novel cross‐Mannich reaction furnishes either enantiomer of unnatural α‐amino acid derivatives in high yield and up to >99 % ee . The one‐pot, three‐component, direct catalytic asymmetric reactions were readily scaled up, operationally simple, and conductible in environmentally benign and wet solvents. The mechanism and stereochemistry of the proline‐catalyzed, one‐pot, three‐component, asymmetric cross‐Mannich reaction are also discussed.