Nickel-Catalyzed Modular Four-Component 1,4-Alkylcarbonylation of 1,3-Enynes to Tetra-Substituted CF₃–Allenyl Ketones

The modular four-component carbonylation of unsaturated hydrocarbons represents an elegant strategy for the one-pot synthesis of complex carbonyl compounds. However, this strategy is currently focused on the 1,2-difunctionalization of olefins or alkynes, and the 1,4-alkylcarbonylation of 1,3-enynes remains unexplored. In this study, we report a Ni-catalyzed 1,4-alkylcarbonylation of CF₃-containing 1,3-enynes under 1 atm of CO, which affords the tetra-substituted CF₃-allenyl ketones with good yields and selectivity. This protocol features mild conditions, broad substrate scope, and acceptable functional group compatibility. Control experiments revealed that the reactivity of oxime esters (regulated by leaving groups) and polarity matching are crucial for the success of this four-component cascade. Preliminary mechanistic studies suggest that the acyl nickel complex is a key intermediate in this transformation.