Bioinspired Electrochemical Cyclization Toward the Divergent Synthesis of Mavacurane- and Akuammiline-type Alkaloids

Electrochemical oxidation has emerged as a powerful and sustainable tool for constructing complex molecular architectures. Herein, we report a divergent electrochemical strategy for the bioinspired synthesis of mavacurane- and akuammiline-type alkaloid frameworks from a common indole–malonate precursor. By tuning the redox mediator, selective N–C or C–C bond formation was achieved. Iodide-mediated electrolysis promoted iodination of the malonate carbanion, followed by intramolecular nucleophilic cyclization to furnish the mavacurane core. In contrast, ferrocene-mediated oxidation generated a malonate-centered radical that underwent regioselective addition to the indole ring, leading to the akuammiline skeleton. Density functional theory calculations revealed that the radical cyclization proceeded via a favorable 5-exo-trig pathway followed by a 1,2-rearrangement. Mechanistic insights from cyclic voltammetry and control experiments further support this mediator-dependent divergence in reactivity. This study highlights the potential of electrochemical control in guiding selective skeletal rearrangements and provides a method for the efficient synthesis of architecturally complex indole alkaloids under mild and tunable conditions.