Metallaphotocatalytic Assembly of Unsymmetrical 1,4-Diketones via Dual Acyl Units: Divergent Initiation of Carboxylic Acids and Aldehydes

Abstract

1,4-Diketones, classic umpolung motifs, have long posed a grand challenge for their efficient synthesis in organic and pharmaceutical synthesis. Herein, we report a nickel/photoredox dual-catalyzed three-component coupling of carboxylic acids, aldehydes, and alkenes. This strategy enables the discriminative introduction of two distinct acyl units through a cascade of hydrogen atom transfer and low-valent nickel-mediated oxidative addition, efficiently delivering unsymmetrical 1,4-diketones. Mechanistic studies, including fluorescence quenching, cyclic voltammetry, and radical trapping, support the versatility of this redox-neutral catalytic mode. This method exhibits broad substrate compatibility, accommodating aliphatic and aromatic carboxylic acids, aldehydes, and bioactive molecules, while also providing rapid access to key pharmaceutical intermediates and bioactive compounds, thus opening avenues to address long-standing synthetic challenges.