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Highly Stereoselective Tandem Aza‐Michael Addition–Enolate Protonation to Form Partially Modified Retropeptide Mimetics Incorporating a Trifluoroalanine Surrogate
Author(s) -
Sani Monica,
Bruché Luca,
Chiva Gema,
Fustero Santos,
Piera Julio,
Volonterio Alessandro,
Zanda Matteo
Publication year - 2003
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.200250711
Subject(s) - protonation , michael reaction , chemistry , nucleophile , tandem , stereoselectivity , nucleophilic addition , solvent , trifluoromethyl , stereochemistry , alkyl , combinatorial chemistry , organic chemistry , catalysis , materials science , ion , composite material
Fine‐tuning of key reaction parameters , such as the solvent and the base used, led to a dramatic improvement in d.r. (from ≈1:1 to 38:1) in a tandem aza‐Michael addition–enolate protonation sequence. Thus, the reaction of α‐amino ester nucleophiles 1 with N ‐(α‐trifluoromethyl)acryloyl‐α‐amino ester acceptors 2 produced an array of partially modified retropeptide mimetics 3 with good to excellent stereocontrol (R, R 1 , R 2 , X, X 1 =alkyl).