General procedure (GP1) for Ugi reactions: larger scale, higher efficiency

In a 25 mL round bottom flask the aldehyde (1.70 eq., typically 1 mmol) was dissolved in a minimal amount of methanol, subsequently the amine (1.70 eq.) was added and the resulting mixture was stirred for 60 min over sodium sulfate for the imine formation (if both components were liquid, no methanol was needed unless the imine would precipitate). The perfluoro acid (1.00 eq.) was dissolved in a minimal amount of methanol and added to the imine at room temperature. The resulting mixture was stirred for 2 min. Subsequently, the isocyanide (1.70 eq.) was added to the stirring mixture. The reaction was stirred for 1–3 d at room temperature. If a precipitate was formed during the reaction, additional methanol was added. If a long perfluorinated chain was present, tetrahydrofuran was utilized in order to homogenize the reaction mixture. The crude reaction mixture was dried under reduced pressure and purified via column chromatography (see General Purification Procedure: F-SPE). Typical yields: 20–85%.