Synergistic Brønsted Base/Photoredox‐Catalyzed Three‐Component Coupling with Malonates to Synthesize δ‐Hydroxy Esters and δ‐Keto Esters

Abstract

Comprehensive SummaryMulticomponent alkene 1,2‐dicarbofunctionalizations (DCFs) have emerged as a powerful strategy to rapidly incorporate both two carbon subunits across one C—C double bond in one step for enhancing molecular complexity and diversity. To the best of our knowledge, there is only one report on photoredox‐catalyzed three‐component DCFs with malonates through the radical−radical cross‐coupling, while photoredox‐catalyzed radical‐polar crossover (RPC)‐type DCFs with malonates were still rare. Herein, we describe a redox‐neutral RPC‐type 1,2‐dialkylation of styrenes with malonates and aldehydes through the synergistic Brønsted base/photoredox catalysis system. This transition‐metal‐free strategy provides an efficient and clean approach to a broad variety of δ‐hydroxy esters and also features exceptionally mild conditions, wide compatibility of substrate scope and functional groups, and high atomic economy. Moreover, three‐component 1,2‐alkylacylation from the same starting materials was achieved in one‐pot manner through such RPC‐type coupling and subsequent two‐electron oxidation process, providing a set of δ‐keto esters of interest in pharmaceutical research.