Visible-Light-Driven 1,4-Hydroalkylation of 1,3-Conjugated Dienes with 1,3-Dicarbonyls

Abstract

The selective radical hydroalkylation of 1,3-dienes, particularly using readily available alkyl radical sources, remains a challenging synthetic transformation, primarily due to the high reactivity of radical intermediates and the presence of multiple reactive sites within the 1,3-diene framework. Herein, we disclose a mild and efficient visible-light-driven 1,4-hydroalkylation of conjugated dienes with perfect atom economy. The key steps of this protocol involve catalytic generation of C-radicals from readily available 1,3-dicarbonyls, followed by a radical 1,4-addition to form the benzyl radicals, which then undergo a single-electron-reduction and final protonation. This method features broad substrate scope, operational simplicity and high efficiency. A variety of readily available malonates, β-ketoesters and diversely substituted ary-1,3-dienes were well accommodated, yielding the corresponding 1,4-hydroalkylated products in generally good yields (50%–82% yields). This approach also broadens the synthetic utility of 1,3-dicarbonyl compounds, facilitating gram-scale synthesis, late-stage modifications of drug-like molecules and further synthetic transformations. As a result, numerous high value-added molecules were obtained, showcasing the synthetic potential of this method. Control experiments revealed that visible-light-irradiation, the photocatalyst and the base are all indispensable for the success of this protocol. Preliminary mechanistic studies, encompassing radical-trapping experiment, deuteroxide quenching experiment, light on-off experiments and Stern-Volmer experiments, support the proposed mechanism.

Keywords

Alkenes / 1,3-Dienes / Difunctionalization / Radical reactions / Photoredox catalysis / 1,3-dicarbonyls / 1,3-dicarbonyl radicals / Alkylation / 1,4-Hydroalkylation

RIGHTS & PERMISSIONS

2025 SIOC, CAS, Shanghai, & WILEY-VCH GmbH