Ammonium Chloride Promoted Ugi Four-Component, Five-Center Reaction of alpha -Substituted alpha -Isocyano Acetic Acid: A Strong Solvent Effect
Conditions have been developed for the multicomponent synthesis of di- and tetrapeptide based on the unique reactivity of alpha -isocyanoacetic acids (including its alpha -substituted derivs.) by an Ugi four-component, five-center reaction. Simply mixing an alpha -isocyanoacetic acid, a carbonyl compd. (aldehyde or ketone), and a secondary amine (ratio: 1:1:2, resp.) in toluene in the presence of 1.5 equiv of ammonium chloride afforded the desired product in good to excellent yield as a mixt. of two diastereomers. For example, peptide deriv. Me2NCH(C6H13)CONHCH(CH2Ph)CONMe2 was prepd. in 96% yield from Ugi reaction of isonitrile C==NCH(CH2Ph)CO2K, aldehyde C6H13CHO and amine Me2NH.HCl. [on SciFinder (R)]
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Bonne, D., Dekhane, M., & Zhu, J. (2004). Ammonium Chloride Promoted Ugi Four-Component, Five-Center Reaction of alpha -Substituted alpha -Isocyano Acetic Acid: A Strong Solvent Effect. Organic Letters, 6(25), 4771–4774. https://doi.org/10.1021/ol0479388
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2004
6
25
4771
4774
CAN 142:94119
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
written in English.
50-00-0 (Formaldehyde); 104-53-0 (3-Phenylpropanal); 108-94-1 (Cyclohexanone); 110-91-8 (Morpholine); 111-71-7 (n-Heptanal); 123-11-5 (4-Methoxybenzaldehyde); 506-59-2 (Dimethylamine hydrochloride); 2043-61-0 (Cyclohexanecarboxaldehyde); 13515-93-0 (Methyl sarcosinate hydrochloride); 39533-32-9; 39687-95-1; 58948-98-4; 63157-14-2; 817636-51-4 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of peptides via ammonium chloride-promoted Ugi reaction of isocyanoacetates, amines and carbonyl compds.); 89099-23-0P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of peptides via ammonium chloride-promoted Ugi reaction of isocyanoacetates, amines and carbonyl compds.); 12125-02-9 (Ammonium chloride) Role: RGT (Reagent), RACT (Reactant or reagent) (prepn. of peptides via ammonium chloride-promoted Ugi reaction of isocyanoacetates, amines and carbonyl compds.); 817636-12-7P; 817636-15-0P; 817636-18-3P; 817636-21-8P; 817636-24-1P; 817636-27-4P; 817636-30-9P; 817636-34-3P; 817636-36-5P; 817636-39-8P; 817636-41-2P; 817636-44-5P; 817636-46-7P; 817636-48-9P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of peptides via ammonium chloride-promoted Ugi reaction of isocyanoacetates, amines and carbonyl compds.)
REVIEWED
OTHER