Modular Access to Quaternary α‑Cyano Carbonyl Compounds via NiH Catalysis

Quaternary α-cyano carbonyl compounds are an important class of molecules in organic synthesis due to their versatility as precursors to essential building blocks and their potential applications in pharmaceutical synthesis. Despite the importance of these sterically congested and highly functionalized structures, the development of a general and practical synthetic platform remains a persistent challenge. Herein, we report a nickel-hydride-catalyzed hydrofunctionalization of α,β-unsaturated nitriles with acyl fluorides as well as their carbamoyl and formyl derivatives. This synthetic protocol enables the modular synthesis of a diverse range of quaternary α-cyano carbonyl compounds, including ketones, amides, and esters, under mild conditions and without the need for an external ligand. Combined DFT and experimental mechanistic studies reveal that the present NiH catalysis proceeds via regioselective hydrometalation, followed by the formation of a nickel-keteneiminate intermediate through rearrangement and subsequent nucleophilic substitution reaction between the nickel-keteneiminate and the carbonyl fluorides.