A new method for the synthesis of 3-alkyl-3-amino-2-oxindoles is reported. These compounds
are prepared in a 3-step procedure using a base-mediated nucleophilic addition of
benzylidene-imine protected α-aminoesters to 2-nitrofluorobenzene as the key step.
The process provides a variety of 3-alkyl-3-amino-2-oxindole analogs in yields of
1-24%. Yields are highest with alanine, phenylalanine and 2-pyridylalanine as the
amino acid starting materials, while 3-pyridylalanine and O-methyltyrosine are less efficiently arylated. Sterically hindered amino acids such
as valine and phenylglycine are for all practical purposes, not substrates for the
key nucleophilic substitution reaction. The resulting 3-alkyl-3-amino-2-oxindoles
are important intermediates for the preparation of drug-like substances. The conversion
of alanine ethyl ester to 3-amino-3-methyl-2-oxindole is described.
alkaloid - amino acid - arylation - nucleophilic aromatic substitution - steric hindrance
- oxindole
