Photoredox Product Selectivity Controlled by Persistent Radical Stability.

The use of photoredox catalysis for the synthesis of small organic molecules relies on harnessing and converting the energy in visible light to drive reactions. Specifically, photon energy is used to generate radical ion species that can be harnessed through subsequent reaction steps to form a desired product. Cyanoarenes are widely used as arylating agents in photoredox catalysis because of their stability as persistent radical anions. However, there are marked, unexplained variations in product yields when using different cyanoarenes. In this study, the quantum yield and product yield of an α-aminoarylation photoredox reaction between five cyanoarene coupling partners and N-phenylpyrrolidine were characterized. Significant discrepancies in cyanoarene consumption and product yield suggested a chemically irreversible, unproductive pathway in the reaction. Analysis of the side products in the reaction demonstrated the formation of species consistent with radical anion fragmentation. Electrochemical and computational methods were used to study the fragmentation of the different cyanoarenes and revealed a correlation between product yield and cyanoarene radical anion stability. Kinetic modeling of the reaction demonstrates that cross-coupling selectivity between N-phenylpyrrolidine and the cyanoarene is controlled by the same phenomenon present in the persistent radical effect.

Enhanced basicity of an electron donor-acceptor complex.

An electron donor-acceptor (EDA) complex forms between 1,4-dicyanobenzene and N-phenylpyrrolidine, which are coupling partners for the α-aminoarylation photoredox reaction. Calculations and experiments demonstrate the EDA complex is a better base than N-phenylpyrroline. A re-analysis of the α-aminoarylation reaction suggests that the EDA complex is a proton acceptor in the reaction.

Photosensitized [2+2]-Cycloadditions of Alkenylboronates and Alkenes.

A new strategy for the synthesis of highly versatile cyclobutylboronates via the photosensitized [2+2]-cycloaddition of alkenylboronates and alkenes is presented. The process is mechanistically different from other processes in that energy transfer occurs with the alkenylboronate as opposed to the other alkene. This strategy allows for the synthesis of an array of diverse cyclobutylboronates. The conversion of these adducts to other compounds as well as their utility in the synthesis of melicodenine C is demonstrated.

Insights into the Mechanism of an Allylic Arylation Reaction via Photoredox-Coupled Hydrogen Atom Transfer.

Despite widespread use as a synthetic method, the precise mechanism and kinetics of photoredox coupled hydrogen atom transfer (HAT) reactions remain poorly understood. This results from a lack of detailed kinetic information as well as the identification of side reactions and products. In this report, a mechanistic study of a prototypical tandem photoredox/HAT reaction coupling cyclohexene and 1,4-dicyanobenzene (DCB) using an Ir(ppy)3 photocatalyst and thiol HAT catalyst is reported. Through a combination of electrochemical, photochemical, and spectroscopic measurements, key unproductive pathways and side products are identified and rate constants for the main chemical steps are extracted. The reaction quantum yield was found to decline rapidly over the course of the reaction. An unreported cyanohydrin side product was identified and thought to play a key role as a proton acceptor in the reaction. Transient absorption spectroscopy (TAS) and quantum chemical calculations suggested a reaction mechanism that involves radical addition of the nucleophilic DCB radical anion to cyclohexene, with cooperative HAT occurring as the final step to regenerate the alkene. Kinetic modeling of the reaction, using rate constants derived from TAS, demonstrates that the efficiency of the reaction is limited by parasitic absorption and unproductive quenching between excited Ir(ppy)3 and the cyanohydrin photoproduct.

Mechanistic Investigations of an α-Aminoarylation Photoredox Reaction.

While photoredox catalysis continues to transform modern synthetic chemistry, detailed mechanistic studies involving direct observation of reaction intermediates and rate constants are rare. By use of a combination of steady state photochemical measurements, transient laser spectroscopy, and electrochemical methods, an α-aminoarylation mechanism that is the inspiration for a large number of photoredox reactions was rigorously characterized. Despite high product yields, the external quantum yield (QY) of the reaction remained low (15-30%). By use of transient absorption spectroscopy, productive and unproductive reaction pathways were identified and rate constants assigned to develop a comprehensive mechanistic picture of the reaction. The role of the cyanoarene, 1,4-dicyanobenzne, was found to be unexpectedly complex, functioning both as initial proton acceptor in the reaction and as a neutral stabilizer for the 1,4-dicyanobenzene radical anion. Finally, kinetic modeling was utilized to analyze the reaction at an unprecedented level of understanding. This modeling demonstrated that the reaction is limited not by the kinetics of the individual steps but instead by scattering losses and parasitic absorption by a photochemically inactive donor-acceptor complex.