Aldehydes as Reducing Agents: Ruthenium Catalyzed Reductive Alkylation Reactions

Aldehydes are the key building block in organic synthesis due to their high availability and diverse reactivity. However, their intrinsic reducing ability remains underutilized. Herein, we report a ruthenium-catalyzed reductive alkylation of ketones and other nucleophiles using aldehydes as both alkylating agents and reductants. This operationally simple protocol proceeds under neat conditions without external hydrogen sources or stoichiometric reductants. The reaction exhibits broad substrate scope, tolerating both aromatic and aliphatic aldehydes and ketones, as well as functional groups sensitive to conventional reductive conditions (alkenes, esters, halides, benzyloxy groups). The protocol was applied to the synthesis of pharmaceutically relevant scaffolds, including Nabumetone and a derivative of pregnenolone acetate. Mechanistic experiments along with DFT-calculations were conducted to investigate mechanism of this transformation. This study highlights the overlooked potential of aldehydes as dual-purpose reagents in redox transformations.