Monitoring and Assessing Iridium-Promoted Photoredox Catalysis by Electrochemistry

Recently, Professor David MacMillan introduced an original light-mediated catalytic process where simple aldehyde substrates undergo coupling with a variety of olefin partners to enantioselectively afford α-alkyl carbonyl adducts. Based on the redox potential values reported for some transient intermediates and on the knowledge-based reactivity of organic radicals, it was suggested that the alkylation of aldehydes proceeds along merged photoredox, organic, and hydrogen-atom transfer (HAT) catalytic subcycles. Inspired by this seminal work, we undertook an electrochemical investigation of the mechanism of the blue light-mediated coupling of propanal with β-pinene. The coupling reaction was performed in dimethoxyethane using Ir(dF(CF3)ppy)2(dtbbpy)](PF6) as the photoredox catalyst, N-methyl-trifluoroethanamine as the enamine catalyst precursor, and 2,4,6-triisopropylbenzenethiol (ArSH) as the hydrogen atom transfer agent. Under these conditions, cyclic voltammetry and chronoamperometry allowed: (a) the determination of the redox potential values of most intermediates involved in the three catalytic cycles, including the iridium complex under its ground and excited states, (b) evidence of the in situ formation of the enamine catalyst obtained by reaction between propanal and N-methyl-trifluoroethanamine, (c) estimation of the equilibrium condensation constant between the aldehyde and the amine, (d) following the enamine oxidation by the excited iridium complex, and (e) revealing the interdependence between the photoredox and the HAT catalytic cycles. Thus, the enamine concentration, monitored by chronoamperometry, accounted for every change on the three catalytic subcycles and allowed us to assess and strengthen the occurrence of key-steps involved in the overall process. This experimental mechanistic investigation, reinforced by gas chromatography analysis of solutions obtained under synthetic conditions, fully supported MacMillan's mechanistic framework. Electrochemical methods appear to be powerful to establish the sequence of reactions triggered by photochemical activation of iridium precursors.