Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

Abstract

In response to the demand for late-stage perfluoroalkylation in synthetic chemistry, we report the synthesis of a series of bench-stable α-(perfluoroalkylsulfonyl)propiophenones. Their application as photocleavable reagents was tested with electron-rich aromatics under metal-free, redox- and pH-neutral conditions to enable late-stage perfluorooctylation, perfluorohexylation, and perfluorobutylation.

Triarylamines as catalytic donors in light-mediated electron donor–acceptor complexes

“…These "dummy group" reagents allow for easy installation of peruoroalkyl (peruorooctyl, peruorohexyl, peruorobutyl and triuoromethyl) group and also alkyl radicals (such as isopropyl and n-hexyl) on electron-rich aromatics and various biologically relevant substrates. 39 However, while a diverse set of peruoroalkyl and alkyl radicals were successfully utilized in this approach, the scope of the substrate is limited to molecules with minimal absorptions overlap to that of the "dummy" group (<290 nm) to achieve high photoconversion yields. It is noteworthy that while the literature pertaining to peruoroalkylation reactions is vast, [40][41][42][43][44] methods for the metal-free C-H peruoroalkylation of aromatic molecules through the use of EDA complexes in the catalytic regime remain limited.…”

“…Having placed the pieces together in our mechanistic puzzle, we proceeded to optimize the proposed conditions and study the scope, while using our previously reported UV-light promoted perfluoroalkylating methodology as a ref. 39 . In the original report, 2 equivalents of the propiophenone-based perfluoroalkylating reagent were used to functionalize electron-rich aromatics under irradiation of a 300 W xenon arc lamp with a long-pass filter of >295 nm, reaching almost quantitative NMR yields for the perfluorohexylation of 1,3,5-trimethoxybenzene.…”

“…In the original report, 2 equivalents of the propiophenone-based per-uoroalkylating reagent were used to functionalize electronrich aromatics under irradiation of a 300 W xenon arc lamp with a long-pass lter of >295 nm, reaching almost quantitative NMR yields for the peruorohexylation of 1,3,5-trimethoxybenzene. 39 Here we aimed to attain the same yields albeit with an electron donor-preferably in catalytic amounts-and using commercial blue LEDs. Firstly, taking the conditions shown in Fig.…”