Semireduction of Secondary Aryl Amides to Imines Using a Mixed Aluminum Hydride Reagent

Aryl amides and imines are among the most commonly encountered functional groups in synthetic organic chemistry, appearing in numerous biologically active pharmaceuticals and natural products. We have developed a new method for the direct semireduction of secondary aryl amides to form the corresponding imines using a combination of the aluminum hydride reducing agents sodium bis(2‐methoxyethoxy)aluminum hydride (Red‐Al) and diisobutylaluminum hydride (DIBAL). This methodology has been successfully demonstrated on a wide variety of substituted benzamide substrates, typically furnishing the imines in over 90% yield with minimal over‐reduction to the corresponding amine. The scope of this transformation has also been extended to other secondary aryl amides, including polycyclic and heterocyclic compounds. As compared to existing methods, this semireduction specifically avoids the use of transition metals or cryogenic temperatures and is therefore amenable to large‐scale synthesis.