Flow photochemistry: Old light through new windows

Abstract

Synthetic photochemistry carried out in classic batch reactors has, for over half a century, proved to be a powerful but under-utilised technique in general organic synthesis. Recent developments in flow photochemistry have the potential to allow this technique to be applied in a more mainstream setting. This review highlights the use of flow reactors in organic photochemistry, allowing a comparison of the various reactor types to be made.

Keywords: cycloaddition; flow chemistry; photocatalysis; photochemistry; photooxygenation.

Figure 1

An immersion-well batch reactor with 125 W medium pressure Hg lamp.

Figure 2

Transmission profile of a 0.05 M solution, ε = 200 M⁻¹ cm⁻¹.

Figure 3

Schematic of a typical microflow photochemical reactor (above) and detail of a triple-channel microflow reactor (below) used for the photooxygenation of citronellol [20].

Figure 4

Schematic of a typical macroflow photochemical reactor (above) and images of the FEP photochemical flow reactor developed by Booker-Milburn and Berry [21].

Scheme 1

[2 + 2] photocycloadditions of enones with enol derivatives.

Scheme 2

Competing reactions in an intramolecular [2 + 2] photocycloaddition.

Scheme 3

Diastereocontrolled cycloaddition of a cyclic enone with cyclopentene.

Scheme 4

Comparison of yields and reaction times for a batch reactor with a microflow system.

Scheme 5

Intramolecular [2 + 2] photocycloaddition.

Scheme 6

Paterno–Büchi reaction of benzophenone with an allylic alcohol.

Scheme 7

Photooxygenation of cyclopentadiene.

Scheme 8

Preparation of the anthelmintic ascaridole 23.

Scheme 9

Production of rose oxide 27 from (−)-β-citronellol (24).

Scheme 10

Photocatalytic alkylation of benzylamine.

Scheme 11

Photocatalytic reduction of 4-nitroacetophenone.

Scheme 12

Conversion of L-lysine to L-pipecolinic acid.

Scheme 13

Photocatalytic hydrodehalogenation.

Scheme 14

Photocatalytic aza-Henry reactions.

Scheme 15

Photocatalytic α-alkylation of aliphatic ketones.

Scheme 16

Decarboxylative photochemical additions.

Scheme 17

Photochemical addition of isopropanol to furanones.

Scheme 18

Photochemical addition of methanol to limonene.

Scheme 19

Light-promoted reduction of flavone.

Scheme 20

Photoreduction of benzophenone with benzhydrol.

Scheme 21

Barton reaction in a microflow system.

Scheme 22

Microflow synthesis of vitamin D₃.

Scheme 23

photochemical chlorination of cyclohexane.

Scheme 24

photochemical cyanation of pyrene.

Scheme 25

Intermolecular [2 + 2] cycloaddition of maleimide (76) and intramolecular [2 + 2] cycloaddition of dimethylmaleimide derivative 78 under flow conditions.

Scheme 26

Intramolecular [5 + 2] cycloaddition of maleimide under flow conditions.

Scheme 27

Intramolecular [5 + 2] cycloaddition as a key step in the synthesis of (±)-neostenine.

Scheme 28

In situ generation of a thioaldehyde by photolysis of a phenacyl sulfide.

Scheme 29

Photodimerisation of maleic anhydride.

Scheme 30

[2 + 2] cycloaddition of a chiral enone with ethylene.

Scheme 31

Intramolecular [2 + 2] cycloaddition of a cyclopentenone.

Scheme 32

Photochemical Wolff rearrangement and cyclisation to β-lactams.

Scheme 33

Photochemical rearrangement of aryl azides.

Scheme 34

Rearrangement of quinoline N-oxides to quinolones.

Scheme 35

Photochemical rearrangement of cyclobutenones.

Scheme 36

Photoisomerisation en route to a vitamin-D derivative.

Scheme 37

Schematic of the Seeberger photooxygenation apparatus and sensitised photooxygenation of citronellol.

Scheme 38

Sensitised photooxygenation of dihydroartemisinic acid.

Scheme 39

Photochemical preparation of CpRu(MeCN)₃PF₆.

Scheme 40

In situ photochemical generation and reaction of a [CpRu]⁺ catalyst.

Scheme 41

Intermolecular alkene–alkyne coupling with photogenerated catalyst.

Scheme 42

PET deoxygenation of nucleosides.

Scheme 43

Photochemical defluorination of DABFT.

Scheme 44

Aromatic azide reduction by visible-light-mediated photocatalysis.

Scheme 45

Examples of visible-light-mediated reactions.

Scheme 46

Visible-light-mediated formation of iminium ions.

Scheme 47

Examples of visible-light-mediated photocatalytic reactions.

Scheme 48

Anhydride formation from a visible-light-mediated process.

Scheme 49

Light-mediated conjugate addition of glycosyl bromide 141 to acrolein.

Scheme 50

Visible-light-mediated photocyclisation to [5]helicene.