A facile synthesis of 4-aryl substituted oxazolo[4,5-c]quinolines has been described via a modified Pictet–Spengler method and using Cu(TFA)₂ as a catalyst. The developed methodology directly functionalizes the C-4 position of oxazoles without the aid of any prefunctionalization, in the presence of the more reactive C-2 position in good yields. The versatility of the established method has been demonstrated by its application in the synthesis of 4-substituted oxazolo-[1,8]naphthyridine ring systems.