Automated Oscillatory Photochemical Reactor for High Throughput Studies of Visible-Light Photoredox Catalysis

Over the past decade, visible-light photoredox catalysis using metal complexes (e.g., polypyridyl complexes of ruthenium and iridium) has steadily been developed as a promising strategy for sustainable and green synthesis of fine chemicals.¹ The relatively long lifetime (~ 1μs) associated with the photoexcited states of metal complexes may result in a bimolecular electron transfer pathway (chemical reaction) instead of deactivation. For instance, photoredox catalysis has successfully been employed for batch scale coupling reactions, reductive dehalogenation, and oxidative hydroxylation.² However, the inverse correlation of the reaction vessel size and penetration depth of the irradiated light has resulted in reaction times in the order of hours. The high surface area to volume ratio offered by microscale flow chemistry technologies has addressed the aforementioned limitation of batch scale photochemical reactors by reducing the characteristic reaction vessel length scale from tens of centimeters to hundreds of micrometers.³ Nevertheless, the direct correlation of the mixing and residence times and limited range of residence times for a pre-defined reactor length in combination with ~ mL reagent volume required per reaction condition make it challenging to employ continuous flow chemistry approaches for high-throughput screening, characterization, optimization and library development of photoredox catalysis reactions.

In this project, capitalizing on the removed residence time limitation and enhanced mixing and mass transfer advantages of oscillatory flow strategy,^4,5 a microscale photochemistry platform is developed for in-flow studies of visible-light photoredox catalysis. Position of the formed droplet (micro-reaction vessel) at the inlet and outlet of the oscillatory flow reactor is detected through a single-point optical detection, integrated within a custom-machined aluminum chuck. The optical feedback provided through the single-point position detection allows for automated switching of the flow direction of the carrier phase to ensure the droplet is always under the same irradiation intensity over the course of the photoredox catalysis process.

The developed experimental platform allowed for the effect of irradiation light intensity on the yield (obtained using in-flow LC/MS) and selectivity of the photoredox catalysis to be precisely characterized by automatic tuning of the irradiation power of the high power LED (through LabView). In addition, utilizing gas as the carrier phase in both sides of a droplet that is pre-formed via a computer-controlled liquid handler (containing the desired photocatalyst) provided sufficient gas molecules during the photoredox catalysis using a reactive gas as an oxidant (e.g., oxygen). Through adjusting the pressure of the carrier phase, the effect of gas concentration (e.g., oxygen pressure) on the photoredox catalysis (e.g., oxidative hydroxylation of phenylboronic acids) was studied.

The proposed experimental setup enables material efficient high-throughput screening and optimization of continuous (e.g., reaction time and concentration of the photocatalyst) and discrete (e.g., different metal complexes, and reaction solvents) parameters associated with a photoredox catalysis process using only 20 μL volume of the solution mixture per experimental condition. The obtained optimized parameters (e.g., photocatalyst molecule structure, concentration, solvent, irradiation power, and reaction time) will then be employed for large-scale (numbered up) continuous synthesis of the desired product under a similar characteristic length scale.

References

(1) Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chemical Reviews 2013, 113, 5322-5363.

(2) Zou, Y.-Q.; Chen, J.-R.; Liu, X.-P.; Lu, L.-Q.; Davis, R. L.; Jørgensen, K. A.; Xiao, W.-J. Angewandte Chemie 2012, 124, 808-812.

(3) Tucker, J. W.; Zhang, Y.; Jamison, T. F.; Stephenson, C. R. J. Angewandte Chemie International Edition 2012, 51, 4144-4147.

(4) Abolhasani, M.; Coley, C. W.; Jensen, K. F. Analytical Chemistry 2015, 87, 11130-11136.

(5) Abolhasani, M.; Bruno, N. C.; Jensen, K. F. Chemical Communications 2015, 51, 8916-8919.