Electroinduced Reductive and Dearomative Alkene-Aldehyde Coupling.

Abstract

The direct coupling of alkene feedstocks with aldehydes represents an expedient approach to the generation of new and structurally diverse C(sp3)-hybridized alcohols that are primed for elaboration into privileged architectures. Despite their abundance, current disconnection strategies enabling the direct coupling of carbon-carbon π-bonds and aldehydes remain challenging because contemporary methods are often limited by substrate or functional group tolerance and compatibility in complex molecular environments. Here, we report a coupling between simple alkenes, heteroarenes and unactivated aliphatic aldehydes via an electrochemically induced reductive activation of C-C π-bonds. The cornerstone of this approach is the discovery of rapid alternating polarity (rAP) electrolysis to access and direct highly reactive radical anion intermediates derived from conjugated alkenes and heterocyclic compounds. Our developed catalyst-free protocol enables direct access to new and structurally diverse C(sp3)-hybridized alcohol products. This is achieved by the controlled reduction of conjugated alkenes and the C2-C3 π-bond in heteroarenes via an unprecedented reductive dearomative functionalization for heterocyclic compounds. Experimental mechanistic studies demonstrate a kinetically biased single-electron reduction of C-C π-bonds over aldehydes. Application of rAP enables chemoselective generation of olefinic radical anion intermediates and avoids undesired saturative overreduction. Overall, this technology provides a versatile approach to the reductive coupling of olefin and heterocycle feedstocks with aliphatic aldehydes, offering straightforward access to diverse C(sp3)-rich oxygenated scaffolds.