Batch versus Flow Photochemistry: A Revealing Comparison of Yield and Productivity

Elliott, Luke D.; Knowles, Jonathan P.; Koovits, Paul J.; Maskill, Katie G.; Ralph, Michael J.; Lejeune, Guillaume; Edwards, Lee J.; Robinson, Richard I.; Clemens, Ian R.; Cox, Brian J.; Pascoe, David D.; Koch, Guido; Eberle, Martin; Berry, Michael S.; Booker‐Milburn, Kevin I.

doi:10.1002/chem.201404347

Cited by 188 publications

(123 citation statements)

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“…With this in mind, it is important to note that the use of automated flow technologies can provide significant levels of standardization of path length, light intensity, and geometry 12,13 for photocatalysis; however, at the same time this technology is not broadly deployed for small-scale applications across academic, pharmaceutical, fragrance, agrochemical, or materials laboratories. 14 …”

Section: Introductionmentioning

confidence: 99%

A General Small-Scale Reactor To Enable Standardization and Acceleration of Photocatalytic Reactions

et al. 2017

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Photocatalysis for organic synthesis has experienced an exponential growth in the past 10 years. However, the variety of experimental procedures that have been reported to perform photon-based catalyst excitation has hampered the establishment of general protocols to convert visible light into chemical energy. To address this issue, we have designed an integrated photoreactor for enhanced photon capture and catalyst excitation. Moreover, the evaluation of this new reactor in eight photocatalytic transformations that are widely employed in medicinal chemistry settings has confirmed significant performance advantages of this optimized design while enabling a standardized protocol.

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Section: Introductionmentioning

confidence: 99%

A General Small-Scale Reactor To Enable Standardization and Acceleration of Photocatalytic Reactions

et al. 2017

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“…It is important to note that the magnitude of attenuation coefficients of the employed chromophores is a key difference between the recently emerging field of photocatalysis (with dyes of ε > 10,000 M −1 cm −1 ) and traditional photochemistry (involving mostly UV irradiation of colourless organic molecules of ε < 1,000 M −1 cm −1 ) [61]. The much lower molar attenuation coefficients of the majority of organic molecules which are directly irradiated by UV light in photochemical processes (e.g., N -alkyl maleimides, ε = ~700 M −1 cm −1 ) [62] lead to more efficient light penetration in batch reactions and therefore only show a limited benefit of using flow reactors for such purposes.…”

Section: Resultsmentioning

confidence: 99%

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

Schachtner

Bayer

Wangelin

2016

Beilstein J. Org. Chem.

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SummaryA home-built microreactor system for light-mediated biphasic gas/liquid reactions was assembled from simple commercial components. This paper describes in full detail the nature and function of the required building elements, the assembly of parts, and the tuning and interdependencies of the most important reactor and reaction parameters. Unlike many commercial thin-film and microchannel reactors, the described set-up operates residence times of up to 30 min which cover the typical rates of many organic reactions. The tubular microreactor was successfully applied to the photooxygenation of hydrocarbons (Schenck ene reaction). Major emphasis was laid on the realization of a constant and highly reproducible gas/liquid slug flow and the effective illumination by an appropriate light source. The optimized set of conditions enabled the shortening of reaction times by more than 99% with equal chemoselectivities. The modular home-made flow reactor can serve as a prototype model for the continuous operation of various other reactions at light/liquid/gas interfaces in student, research, and industrial laboratories.

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“…This highlights once again the value of flow photochemistry for scaling-up high dilution/low quantum yield reactions-this would simply not be possible on laboratory batch scale. [10] We then investigated the Pd-catalyzed Tsuji-Trost type reaction of (AE)-8 with acetate as nucleophile,t his proceeded in excellent yield (81 %) to give as ingle diastereomer of the (S N 2')ring-opened amine (AE)-9.Itwas interesting to observe that after 3h the regioisomeric ratio (NMR) of S N 2' to S N 2 ring-opened product was 1:15. However,a fter 16 hn one of the S N 2r ing opened product remained, indicating that this reaction is under thermodynamic control via the initially formed S N 2p roduct.…”

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confidence: 99%

A Short Synthesis of (±)‐3‐Demethoxyerythratidinone by Ligand‐Controlled Selective Heck Cyclization of Equilibrating Enamines

Blackham

Booker‐Milburn

2017

Angewandte Chemie

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As hort, 5-step total synthesis of (AE)-3-demethoxyerythratidinone from as imple pyrrole derivative is described. Features include the formation of gram quantities of ak ey tricylic aziridine from ac hallenging photochemical cascade reaction through the use of flowphotochemistry.The final step involved ah ighly unusual Heckc yclization whereby ligand control enabled efficient formation of the natural product in 69 %y ield from the minor isomer present in an equilibrating mixture of labile enamines.The alkaloid (+ +)-3-demethoxyerythratidinone 1 is one of over 100 natural products produced by the Erythrina genus of flowering plants. [1] The Erythrina alkaloids display ab road range of pharmacological activities including hypotensive, sedative,n euromuscular blocking,C NS depressing and curare-like activities.T he key structural feature of this family is the tetracyclic tetrahydroisoquinoline core.S ince the first total synthesis of 1 by Tsuda in 1984, [2] this tetracyclic alkaloid has been used by others in order to demonstrate the utility of various synthetic methodologies.[3] Av ery elegant synthesis was recently reported by Reisman, where chiral sulfinyl imine chemistry was used to control the stereochemistry of the key quaternary center, [3d] giving (À)-3-demethoxyerythratidinone in just six steps overall (Figure 1).Individually both photochemical and Pd-catalyzed crosscoupling methodologies have been shown to be powerful techniques in organic synthesis as well as valuable tools in the synthesis of complex molecular architectures.[4] We have previously reported the photochemical transformation of simple N-butenyl-substituted pyrroles into complex tricyclic aziridines 2.[5] We recently demonstrated that these strained photochemical products undergo arange of thermal and Pdcatalyzed ring-opening/annulation reactions to produce ab road range of fused polyheterocycles,i nj ust two steps from simple pyrroles (Scheme 1).[6] We were therefore keen to exploit the functionality and inherent strain in these aziridines as part of an alkaloid synthesis,i np articular the aziridine carboxylates 3.H erein we report as hort total synthesis of (AE)-1 utilizing ah ighly unusual and selective, ligand controlled intramolecular Heck-reaction onto one of apair of equilibrating enamine intermediates. Our initial strategy to 1 (Scheme 1) involved aryl cyclization onto the iminium ion 4 which itself would be generated by in situ decarboxylation of the amino acid 5.[7] Although iminium ion cyclizations are one of the most frequently used approaches to such alkaloids, [8] these have usually involved the intermediary of N-acyliminium ions.[9] Ther equisite amino-acid 5 should be obtained by Pd 0 -catalyzed acetate ring-opening of the aziridine 3 followed by N-alkylation with the iodide 6.Irradiation of pyrrole 7 (254 nm) gave the aziridine (AE)-8 in a39% yield (Scheme 2). As before,wefound that this two- photon process suffers from low productivity due to al ikely low overall quantum yield and as such was limited to ca. 60 ...

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Batch versus Flow Photochemistry: A Revealing Comparison of Yield and Productivity

Cited by 188 publications

References 53 publications

A General Small-Scale Reactor To Enable Standardization and Acceleration of Photocatalytic Reactions

A General Small-Scale Reactor To Enable Standardization and Acceleration of Photocatalytic Reactions

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

A Short Synthesis of (±)‐3‐Demethoxyerythratidinone by Ligand‐Controlled Selective Heck Cyclization of Equilibrating Enamines

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