SummarySynthetic 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.

The use of flow photochemistry and its apparent superiority over batch has been reported by a number of groups in recent years. To rigorously determine whether flow does indeed have an advantage over batch, a broad range of synthetic photochemical transformations were optimized in both reactor modes and their yields and productivities compared. Surprisingly, yields were essentially identical in all comparative cases. Even more revealing was the observation that the productivity of flow reactors varied very little to that of their batch counterparts when the key reaction parameters were matched. Those with a single layer of fluorinated ethylene propylene (FEP) had an average productivity 20% lower than that of batch, whereas three-layer reactors were 20% more productive. Finally, the utility of flow chemistry was demonstrated in the scale-up of the ring-opening reaction of a potentially explosive [1.1.1] propellane with butane-2,3-dione.

The development of a highly compact and powerful reactor for synthetic organic photochemistry is described enabling a 10-fold reduction in reaction times, with up to 30% more power efficiency than previous fluorinated ethylene propylene tube reactors. Two reactions gave over 1 kg of product in 24 h. Two other reactions had productivities of 4 and 8 kg in 24 h. The reactor consists of a succession of quartz tubes connected together in series and arranged axially around a variable power mercury lamp. This compact and relatively simple device can be safely operated in a standard fumehood.

Time Dependent Density Functional Theory (TD-DFT) has been used to assist the design and synthesis of a series thioxanthone triplet sensitizers. Calculated energies of the triplet excited state (ET) informed both the type and position of auxochromes placed on the thioxanthone core, enabling fine-tuning of the UV-Vis absorptions and associated triplet energies. The calculated results were highly consistent with experimental observation in both the order of the λmax and ET values. The synthesised compounds were then evaluated for their efficacies as triplet sensitizers in a variety of UV and visible light preparative photochemical reactions. The results of this study exceeded expectations; in particular [2+2] cycloaddition chemistry that had previously been sensitized in the UV was found to undergo cycloaddition at 455 nm (blue) with a 2 to 9-fold increase in productivity (g/h) relative to input power. This study demonstrates the ability of powerful modern computational methods to aid the design of successful and productive triplet sensitized photochemical reactions. 1 3,3'-MeOTX 354 292 289 298 e 10 ± 3 ps 862 ± 40 ns 0.93 2 3,3'-FTX 362 290 285 289 e 10.5 ± 1.8 ps 456 ± 25 ns 0.92 3 3-MeOTX 367 284 279 283 e 31 ± 4 ps 867 ± 50 ns >0.9 4 3-FTX 370 282 277 282 e 21 ± 3 ps 520 ± 25 ns 0.83 5 TX (R/R'=H) 380 274 268 274 e 70 ps 20 760 ± 30 ns 0.76 17 6 ITX (R'=H, R = 2-i Pr) 385 270 263 266 e 220 ± 8 ps 880 ± 50 ns 0.86 7 2-FTX 388 263 257 261 e 270 ± 10 ps 585 ± 20 ns 0.81 8 4-MeOTX 385 267 260 263 e 1.9 ± 0.4 ns 1.8 ± 0.3 μs 0.70 9 2-MeOTX 399 252 245 242 f 3.3 ± 0.2 ns 1.7 ± 0.6 μs 0.83 10 2-F,2'-MeOTX 408 242 235 235 f 9.1 ± 0.7 ns 1.2 ± 0.2 μs 0.62 11 2,2'-MeOTX 415 235 227 231 f 6.2 ± 0.5 ns 863 ± 60 ns 0.66

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Supporting InformationThe supporting information is available free of charge on the ACS Publications website at DOI: Synthetic methods, characterization, crystallographic and computational modeling data.

A simple method for the accurate calculation of optimal flow rates for photochemical reactions from optimized batch results is described and demonstrated in the scale-up of three challenging examples.

N-Ts and N-Boc derivatives of 1,2-diamines and 1,2-amino alcohols are shown to undergo efficient Pd(II)-catalyzed aza-Wacker reactions with a large range of electron-deficient alkenes. The resulting enamine intermediate generally undergoes cyclization with the second heteroatom to form 1,3-heterocycles. The sequence facilitates the rapid synthesis of saturated oxazolidines, imidazolidines, and their derivatives. Use of N-L-valinol derivatives results in highly diastereoselective reactions, where the net stereochemical outcome diverges between N-Ts and N-Boc.