Photoredox catalyzed C(sp³)–H functionalization is a powerful technique to access derivatized heterocycles under mild conditions with wide functional group tolerance. However, the kinetics and rate-determining steps of such reactions are currently poorly understood: the orders in reaction components are specific to reaction variables including light intensity, catalyst and reaction concentration, and reaction setup. Flow chemistry allows for fine control of these variables when conducting photoredox reactions, along with higher surface-area-to-volume ratios, enhanced light penetration and improved efficiencies and reproducibility over their batch counterparts.

This presentation will describe the development of a photoredox catalysed C(sp³)–H functionalization reaction of N-aryl pyrrolidines with radical acceptors in continuous flow. We used variable time normalization analysis (VTNA) to guide the development of photon-saturated reaction conditions and determine the reaction order. Through kinetic experiments under this photon-saturated regime, we identified the rate determining step of this catalytic cycle as the single electron transfer between N-aryl pyrrolidines and the excited state of the iridium photocatalyst. We then investigated the effect of different substrates on the reaction rate, finding trends in the aryl substitution patterns of N-aryl pyrrolidines and different nitrogen heterocycles. Reaction profiles, cyclic voltammetry and fluorescence quenching studies were used to correlate the reaction rate for different substrates to the oxidation potential of that substrate. This has uncovered understanding into the chemistry of radical formation under iridium-catalyzed photoredox conditions. Computational investigations have sought to explain these trends in oxidation potentials, providing general insights into the formation of α-nitrogen radicals and the chemoselectivity of such transformations.

Thomas Heinis

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