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.

Keywords: innate functionalization; late-stage functionalization; light-mediated perfluoroalkylation; perfluoroalkyl sulfinates; α-(perfluoroalkylsulfonyl)propiophenones.

Scheme 1

Envisioned Minisci perfluoroalkylation facilitated by “dummy group” reagents 1a–c.

Scheme 2

Control experiments for the nucleophilic substitution of perfluoroalkylsulfinates 2 and halogenated electrophilic partners.

Scheme 3

Left: isolated yields of synthesized perfluoroalkylating reagents: perfluorobutyl (1a), perfluorohexyl (1b), and perfluorooctyl (1c) analogues (after conversion of byproduct); middle: gram amounts of perfluorooctyl product 1c; right: UV–vis absorption of reagents 1b and 1c.

Scheme 4

Radical trapping experiment with 1,1-diphenylethylene (7) and 1b confirming the initially proposed mechanism.

Scheme 5

Demonstrative scope for the perfluoroalkylation of aromatics. Isolated yields are shown in parentheses.