Ugi-4CR and Nucleophilic Aromatic Substitution

Zhu et al. [103] reported a fadle access to biologically relevant macrocycles bearing an endo diaryl ether bond by means of a tandem Ugi-4CR/SNAr. The reaction between 3-hydroxyphenylacetic [or 3-(3-hydroxyphenyl)propionic] acid, aldehydes, amines, and isocyanide 197 gave the expected dipeptide derivatives 198 as a 1 1 mixture of diastereoisomers. The reaction gave high yields when performed in tri- 

3 See for example Kocienski, P. J., Protecting Groups, Thieme, Stuttgart, New York, 1994. 

22 Hulme, C. Nixey, T. Curr. Opin. Drug Disc. 2003, 6, 921-929. 

66 Bossio, R. Marcaccini, S. Paoli, P. Papaleo, S. Pepino, R. Polo, C. Liebigs Ann. Chem. 1991, 843—849. Bossio, R. Marcaccini, S. Papaleo, 

72 Faggi, C. Garcia-Valverde, M. Marcaccini, S. Pepino, R. Pozo, 

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