Direct Intermolecular C-H Functionalization Triggered by 1,5-Hydride Shift: Access to N-Arylprolinamides via Ugi-Type Reaction.

A novel Ugi-type reaction triggered by 1,5-hydride shift has been established, giving access to N-arylprolinamides and related compounds in high atom economy and good yields. This is an example of a two starting material-three component reaction. The benzyl alcohol substrate 1 acts as a dual synthon, which upon treatment with a Brønsted acid affords iminium ion and water. Nucleophilic attack at the iminium ion by the third component isocyanide, followed by hydrolysis with the endogenic water, gives the Ugi-type reaction products. The reaction proceeds under mild conditions and is tolerable to a broad scope of substrates.