Photon Equivalents as a Parameter for Scaling Photoredox Reactions in Flow: Translation of Photocatalytic C−N Cross‐Coupling from Lab Scale to Multikilogram Scale

Abstract

With the development of new photocatalytic methods over recent decades,t he translation of these chemical reactions to industrial-production scales using continuous-flow reactors has become at opic of increasing interest. In this context, we describe our studies towarde lucidating an empirically derived parameter for scaling photocatalytic reactions in flow. By evaluating the performance of ap hotocatalytic CÀNc ross-coupling reaction across multiple reactor sizes and geometries,i tw as demonstrated that expressing product yield as afunction of the absorbed photon equivalents provides apredictive,empirical scaling parameter.Through the use of this scaling factor and characterization of the photonic flux within each reactor,t he cross-coupling was scaled successfully from the milligram scale in batch to am ultikilogram reaction in flow.

Photoactive Nickel Complexes in Cross‐Coupling Catalysis

“…Whilst aryl aminations yielding anilines received particular attention, [20, 37] C−N bond forming reactions by combined photoredox and nickel catalysis further include the synthesis of indolines [19] and sulfonamides [21] . Selected photodriven C−N coupling reactions have been performed on the kilogram scale [38] …”

“…[21] Se- lected photodriven CÀNc oupling reactions have been performed on the kilogram scale. [38] CÀOa nd CÀSc oupling reactions using aryl halidesa nd alcohols or thiols leadingt oa ryl esters ( Figure 2b) [3] and thioethers ( Figure 2c) [23] have been reported to proceed with broad substrate scope, yet very disparate reactionp athways have been proposed by differenti nvestigators. In one case, thioetherifica-tion was discovered serendipitously when using hypervalent alkylsilicates for the photochemical formation of alkyl radicals.…”

Harnessing Photoexcited Redox Centers of Semiconductor Photocatalysts for Advanced Synthetic Chemistry

“…Another challenge is the activation of small molecules, including methane or ethane CH oxidation for synthetic transformations. [ 122–125 ] We believe that semiconductor photocatalyzed synthetic transformations will attract increasing interest, and new forms of semiconductors with the required redox window and reactivity will emerge for the production of valuable chemicals and pharmaceuticals.…”

A Droplet Microfluidic Platform for High-Throughput Photochemical Reactions

“…From a material consumption standpoint, droplet microfluidics screens are typically performed at nanoliter to femtoliter scale, which translates to a reduction in starting material usage by six to eight orders of magnitude relative to a traditional multiwell plate-based screen. Droplet microfluidics is also well suited for photocatalytic reactions, as the micrometer dimension of the reaction vessel allows for high photon flux through the reaction channel in an analogous manner to the narrow tubing employed in flow reactors (18)(19)(20). Here, we report advances towards a droplet microfluidic/MS platform to enable picomole-scale discovery of visible light-driven reactions and provide robust translatability to millimole flow scale-up processes.…”