Photo-Fries Rearrangement in Flow: Ways to Access 2-Acylphenols and Opportunities for Reaction Development
Yen-Ku Wu
Department of Applied Chemistry, National Yang Ming Chiao Tung University
Hsinchu, Taiwan
E-mail: yenkuwu@nycu.edu.tw
The Photo-Fries rearrangement was first discovered by Anderson and Reese over fifty years ago.1a Mechanistically, when a phenolic ester is photoexcited, it undergoes homolytic cleavage, forming a transient radical pair (phenoxyl and carbonyl).1b The productive combination of these radicals initially offers dearomatized intermediates, which then tautomerize into the corresponding ortho- or para-acylated products. Besides the possible formation of mixtures, the reaction can be further complicated by internal light filtering of 2-
acylphenol,1c by which the effective light absorbance gradually diminishes as the reaction proceeds (i.e. the concentration of the rearranged product increases). To address these challenges, a flow edition of photo-Fries rearrangement for the synthesis of 2-acylphenols in an aqueous micellar medium was developed.2a We take advantage of a narrow channel reactor and micelle-induced confinement effect to refine both the efficiency and selectivity of the parent photoreaction. Furthermore, I would like to discuss our recent efforts to exploit photoflow-Fries processes for the synthesis of fine chemicals and for the exploration of new reaction manifolds.2b,c
References
1. (a) Anderson, J. C.; Reese, C. B. Proc. Chem. Soc., London 1960, 217. (b) Toldo, J.
M.; Barbatti, M.; Goncalves, P. F. B. Phys. Chem. Chem. Phys. 2017, 19, 19103. (c)
Primo, J.; Tormo, R.; Miranda, M. A. Heterocycles 1982, 19, 1819.
2. (a) Chien, C.-C.; Kao, S.-C.; Chen, C.-J.; Wu, Y.-K. Chem. Commun. 2020, 56,
15470. (b) Chang, C.-Y.; Chen, C.-J.; Huang, S.-H.; Kao, S.-C.; Wu, Y.-K. Asian J. Org.
Chem. 2022, 11, e202100721. (c) Lin, X.-J.; Wang, C.-L.; Peng, C.-H.; Liu, H.-J.; Wu,
Y.-K. Chem. Asian J. 2024, 19, e202400269.
Keywords: organic synthesis; rearrangement; polyphenols; photoirradiation