Oxidative Fluorination of Heteroatoms Enabled by Trichloroisocyanuric Acid and Potassium Fluoride

Abstract

In synthetic method development, the most rewarding path is seldom a straight line. While our initial entry into pentafluorosulfanyl (SF₅ ) chemistry did not go according to plan (due to inaccessibility of reagents such as SF₅ Cl at the time), a "detour" led us to establish mild and inexpensive oxidative fluorination conditions that made aryl-SF₅ compound synthesis more accessible. The method involved the use of potassium fluoride and trichloroisocyanuric acid (TCICA)-a common swimming pool disinfectant-as opposed to previously employed reagents such as F₂ , XeF₂ , HF, and Cl₂ . Thereafter, curiosity led us to explore applications of TCICA/KF as a more general approach to the synthesis of fluorinated Group 15, 16, and 17 heteroatoms in organic scaffolds; this, in turn, prompted SC-XRD, VT-NMR, computational, and physical organic studies. Ultimately, it was discovered that TCICA/KF can be used to synthesize SF₅ Cl, enabling SF₅ chemistry in an unexpected way.

Keywords: Gas-Reagent-Free; Inorganic Fluorine Chemistry; Oxidative Fluorination; Pentafluorosulfanyl; Trichloroisocyanuric Acid.

Figure 1

Story arc of our unexpected foray into oxidative fluorination of heteroatoms with the TCICA/KF approach.

Figure 2

Reaction discovery, representative substrate scope, select applications, and opportunities for development surrounding the TCICA/KF approach to the synthesis of aryl‐SF₅, aryl‐SF₄R, and aryl‐SF₃ compounds.

Figure 3

Reaction discovery, representative substrate scope, structural/spectroscopic analyses, and opportunities for development surrounding the TCICA/KF approach to the synthesis of aryl‐SeF₃, aryl‐TeF₅, and aryl‐TeF₄CF₃ compounds.

Figure 4

Reaction discovery, representative substrate scope, Hammett and structural analyses, and opportunities for development surrounding the TCICA/KF approach to the synthesis of aryl‐SF₂R_f and aryl‐SeF₂R_f compounds.

Figure 5

Reaction discovery, representative substrate scopes, structural analyses, and opportunities for development surrounding the TCICA/KF approach to the synthesis of aryl‐IF₂ and aryl‐IF₄ compounds.

Figure 6

Reaction discovery, prior art, and opportunities for development surrounding the first gas‐reagent‐free synthesis of SF₅Cl.

Figure 7

Highlighting examples of recent applications of the TCICA/KF combination to oxidative fluorination in other laboratories.[ ⁶¹ , ⁶² , ⁶⁶ , ⁷³ ]