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Organocatalytic Enantioselective Mukaiyama–Mannich Reaction of Isatin‐Derived Ketimines for the Synthesis of Oxindolyl‐ β 3, 3 ‐Amino Acid Esters
Author(s) -
Hajra Saumen,
Laskar Sujay,
Jana Bibekananda
Publication year - 2019
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.201903512
Subject(s) - enantioselective synthesis , isatin , chemistry , aldimine , mannich reaction , ketene , catalysis , silylation , organic chemistry , organocatalysis , combinatorial chemistry
Mukaiyama–Mannich reactions of ester enolate equivalents with aldimines have been elegantly used for the asymmetric synthesis of β‐amino acids; nevertheless, the corresponding asymmetric reaction employing ketimines are unexplored. Herein, the first organocatalytic enantioselective Mukaiyama–Mannich reaction employing isatin‐derived ketimines with unsubstituted silyl ketene acetals is disclosed towards the scalable synthesis of 2‐oxoindolinyl‐ β 3, 3 ‐amino acid esters at room temperature with excellent enantioselectivities ( ee >99.5 %). Ultra‐low catalyst loadings (as low as 250 ppm) could be used for the quantitative product formation with high enantiopurity. The synthetic utility of this protocol has been showcased in the short formal synthesis of pharmaceutically demanded (+)‐AG‐041R, a potent gastrin/CCK‐B receptor antagonist.