A Unified Strategy for Arylsulfur(VI) Fluorides from Aryl Halides: Access to Ar-SOF3 Compounds

Abstract

A convenient protocol to selectively access various arylsulfur(VI) fluorides from commercially available aryl halides in a divergent fashion is presented. Firstly, a novel sulfenylation reaction with the electrophilic N-(chlorothio)phthalimide (Cl-S-Phth) and arylzinc reagents afforded the corresponding Ar-S-Phth compounds. Subsequently, the S(II) atom was selectively oxidized to distinct fluorinated sulfur(VI) compounds under mild conditions. Slight modifications on the oxidation protocol permit the chemoselective installation of 1, 3, or 4 fluorine atoms at the S(VI) center, affording the corresponding Ar-SO₂ F, Ar-SOF₃ , and Ar-SF₄ Cl. Of notice, this strategy enables the effective introduction of the rare and underexplored -SOF₃ moiety into various (hetero)aryl groups. Reactivity studies demonstrate that such elusive Ar-SOF₃ can be utilized as a linchpin for the synthesis of highly coveted aryl sulfonimidoyl fluorides (Ar-SO(NR)F).

Keywords: heterocycles; sulfinyl trifluorides; sulfonimidoyl fluorides; sulfonyl fluorides; tetrafluorosulfanyl chlorides.

Figure 1

A) Various fluorinated arylsulfur(VI) compounds with different levels of fluorination and their precursors for synthesis. B) Previous work for synthesis of Ph‐SOF₃. C) Our unified strategy for selective synthesis of Ar‐SO₂F, Ar‐SOF₃, Ar‐SF₄Cl, and Ar‐S(O)(NR)F from aryl halides.

Scheme 1

Synthesis of Ar‐SOF₃ from aryl halides. Reaction conditions: The Ar‐S‐Phth 3 was firstly synthesized based on the general methods from corresponding aryl halides. After purification through column chromatography, 3 (0.1 mmol), TCICA (0.9 mmol), KF (0.16 mmol), TFA (0.2 mmol) were stirred in MeCN (1 mL), RT for 24 h. Yields in parentheses correspond to those from Ar‐S‐Phth (based on ¹⁹F NMR spectra, PhCF₃ as internal standard); yields outside the parenthesis correspond to those from 1. [a] Reaction conditions: 3 s was prepared from the reaction of N‐chlorophthalimide with 2‐pyrimidinethiol.

Scheme 2

Synthesis of Ar‐SO₂F from aryl halides. Reaction Conditions: The Ar‐S‐Phth 3 was firstly synthesized based on the general methods from corresponding aryl halides. After purification through column chromatography, 3 (0.1 mmol), TCICA (0.9 mmol), KF (0.16 mmol), MeOH (0.2 mmol) were stirred in MeCN (1 mL), RT for 24 h. Overall yields from 1.

Scheme 3

Synthesis of Ar‐SF₄Cl from aryl halides. Reaction Conditions: The Ar‐S‐Phth 3 was firstly synthesized based on the general methods from corresponding aryl halides. After purification through column chromatography, 3 (0.2 mmol), TCICA (3.6 mmol), KF (6.4 mmol), TFA (0.02 mmol) were stirred in MeCN (2 mL), RT for 24 h. Yields in parentheses correspond to those from Ar‐S‐Phth (based on ¹⁹F NMR spectra, PhCF₃ as internal standard); yields outside the parenthesis correspond to those from the parent Ar‐X. [a] The Ar‐S‐Phth precursor was prepared from the reaction of N‐chlorophthalimide with 2‐pyrimidinethiol.

Scheme 4

Exploration of reactivity of Ar‐SOF₃ with amines. Reaction conditions: ArSOF₃ (0.1 mmol), amine (0.25 mmol), NEt₃ (0.3 mmol) in MeCN (1 mL) at RT for 18 h. Yields of isolated products.