A Reductive Ugi Reaction with Carboxylic Acids Replacing Aldehydes.

Here, we report a Ti(IV)-catalyzed reductive Ugi reaction in which two distinct carboxylic acids replace aldehyde and carboxylic acid components. The Ti(IV) catalyst exhibits dual roles: promoting the deoxygenative imination of carboxylic acids through its oxophilicity and acting as a Lewis acid to activate imine intermediates for the the Ugi reaction. The addition of methanol quenches excess hydrosilane, ensuring an efficient tandem process. This one-pot tandem reaction expands the carboxylic acid utility in MCRs, offering a platform for drug discovery, functional materials, and natural product synthesis.