A Rapid Access to Biaryl Ether Containing Macrocycles by Pairwise Use of Ugi 4CR and Intramolecular SNAr-Based Cycloetherification

An Ugi reaction promoted by ammonium chloride in aprotic solvent is documented here for the first time. From readily accessible starting materials, macrocycles with an endo aryl-aryl ether bond are synthesized in only two steps, Ugi four-component reaction (Ugi 4CR) and an intramol. SNAr reaction. The nitro group serves as an activator for the macrocyclization and provides a handle for the introduction of functional group diversity. For example, dipeptide amide I was obtained in an Ugi 4CR from isonitrile II, PhCHO, PhCH2NH2 and 3-hydroxyphenylacetic acid in the presence of NH4+Cl- in toluene at 0 Deg for 20 h. Cycloetherification of I took place in the presence of K2CO3 in DMF for 3 h to give macrocycle III in 80% yield. [on SciFinder (R)]


Published in:
Organic Letters, 3, 25, 4079-4082
Year:
2001
Keywords:
Note:
CAN 136:118732
34-3
Amino Acids, Peptides, and Proteins
Institut de Chimie des Substances Naturelles,CNRS,Gif-sur-Yvette,Fr.
Journal
1523-7060
written in English.
75-31-0 (Isopropylamine); 78-84-2 (Iso-butyraldehyde); 100-46-9 (Benzylamine); 100-52-7 (Benzaldehyde); 104-53-0 (Benzenepropanal); 104-94-9 (p-Methoxyaniline); 109-73-9 (n-Butylamine); 111-71-7 (n-Heptanal); 120-20-7; 459-57-4 (4-Fluorobenzaldehyde); 621-37-4; 621-54-5; 3173-56-6 (Benzyl isocyanate); 15017-52-4; 58885-60-2 Role: RCT (Reactant), RACT (Reactant or reagent) (prepn. of biaryl ether-contg. macrocycles by Ugi four component reaction and intramol. SNAr-based cycloetherification); 20274-69-5P; 42564-51-2P; 389634-80-4P; 389634-81-5P; 389634-82-6P; 389634-83-7P; 389634-84-8P; 389634-85-9P; 389634-86-0P; 389634-87-1P; 389634-88-2P; 389634-89-3P; 389634-97-3P; 389634-98-4P; 389634-99-5P; 389635-00-1P; 389635-01-2P; 389635-02-3P; 389635-04-5P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (prepn. of biaryl ether-contg. macrocycles by Ugi four component reaction and intramol. SNAr-based cycloetherification); 389635-03-4P; 389635-05-6P; 389635-06-7P; 389829-05-4P; 389829-08-7P; 389829-10-1P; 389829-13-4P; 389829-15-6P; 389829-18-9P; 389829-21-4P; 389829-24-7P; 390360-55-1P; 390360-57-3P; 390360-59-5P; 390360-61-9P; 390360-63-1P; 390360-65-3P; 390360-67-5P; 390360-69-7P; 390360-71-1P; 390360-73-3P; 390360-75-5P; 390360-77-7P Role: SPN (Synthetic preparation), PREP (Preparation) (prepn. of biaryl ether-contg. macrocycles by Ugi four component reaction and intramol. SNAr-based cycloetherification)
Laboratories:




 Record created 2010-11-25, last modified 2018-09-13


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