Abstract
Highly functionalized structural motifs with extended chiral carbon chains are prevalent in a wide range of bioactive compounds and play critical roles in the production of various functionalized molecules. Here, we describe a nickel-catalyzed asymmetric radical-based electrochemical functionalization of silyl polyenolates at α-, γ-, ε-, and η-positions. Driven by electric current, this methodology provides a sustainable route to access enantioenriched dicarbonyls via vinylogous radical pathways. It demonstrates excellent functional groups tolerance, mild reaction conditions, broad substrate compatibility, formation of quaternary stereocenters at remote positions, and high levels of regio- and enantioselectivity (up to 98% enantiomeric excess). Mechanistic investigations indicate that ferrocene-based electron transfer mediators are pivotal in the anodic oxidation process, facilitating the generation of nickel-bound α-carbonyl radicals while suppressing the undesired oxidation of silyl polyenolates, thus guiding the selection of mediators for electrocatalytic systems. The versatility of catalytic asymmetric electrosynthesis is highlighted by the preparation of valuable enantioenriched building blocks and the total synthesis of (-)-ethosuximide.