Nickel-catalysed regio- and stereoselective acylzincation of unsaturated hydrocarbons with organozincs and CO

Carbometallation of unsaturated hydrocarbons is one of the most straightforward functionalizations of carbon–carbon unsaturated bonds; however, the analogous acylmetallation remains a significant synthetic challenge. Here, we disclose the nickel-catalysed acylzincation of ynamides, oxabicyclic alkenes and α,β-unsaturated ketones with organozinc reagents under 1 atm of CO, featuring excellent functional group tolerance, a broad substrate scope and mild conditions. The acyl functionality generated in situ from an organozinc reagent can be viewed as a nucleophilic synthon, and the corresponding acylzincation intermediate is trapped via intermolecular reaction with electrophiles. Alternatively, the intermediate can undergo an intramolecular Truce–Smiles rearrangement or aldol condensation to afford tetrasubstituted enones, multisubstituted benzocyclohexane derivatives and cyclopentenones. This method is applied to the formal synthesis of the anthracyclinone antibiotic daunomycinone, as well as to prepare functionalized 1,3-dienones possessing aggregation-induced emission activity. The syn metallation of acyl nickel intermediates with unsaturated hydrocarbons allows for the complete regioselective and highly stereoselective formation of functionalized zinc intermediates. Furthermore, density functional theory calculations show that acylmetallation is lower in energy than alkylmetallation, and demonstrates that favourable interaction energies lead to a lower energy transition state for formation of the major regioisomer.