Electrochemical assembly of isoxazoles a four-component domino reaction

• Published in: Chemical science (Cambridge) 2024-01, Vol.15 (3), p.1117-1122
• Main Authors: Zhao, Yuanyuan, Li, Xinyue, Homölle, Simon L, Wang, Bin, Ackermann, Lutz
• Format: Article
• ISSN: 2041-6520; 2041-6539
• DOI: 10.1039/d3sc05946d

Multicomponent domino reactions via electrochemical annulations have emerged as a robust strategy for the rapid assembly of heterocyclics. Herein, an electrochemical annulation via a [1 + 2 + 1 + 1] four-component domino reaction was accomplished in a user-friendly undivided cell setup to assemble valuable five-membered isoxazole motifs. Our approach is characterized by a high level functional group tolerance and operational simplicity, avoiding the tedious and time-consuming preparation of pre-functionalized substrates. Detailed mechanistic studies were conducted including isotopic labeling, kinetic studies, cyclic voltammetry (CV) analysis, and intermediate characterization, providing support for a radical pathway. Electrochemical annulation via a four-component domino reaction enabled the assembly of valuable 3,5-di-substituted isoxazole motifs. The exceptional versatility of this approach is highlighted by its capacity for late-stage diversification.