Base-Catalyzed Intramolecular Defluorination/O-Arylation Reaction for the Synthesis of 3-Fluoro-1,4-oxathiine 4,4-Dioxide

Abstract

A novel process involving base-catalyzed intramolecular defluorination/O-arylation of readily available α-fluoro-β-one-sulfones was realized and provided a series of 3-fluoro-1,4-oxathiine 4,4-dioxide derivatives in good to excellent yields. Unlike traditional defluorination reactions with stoichiometric base as the deacid reagent, this process is triggered by a catalytic amount of base (TMG: tetramethylguanidine) and molecular sieves serve as both an adsorbent to remove HF acid and an activator to assist C–F bond cleavage.

Key words

base catalysis - defluorination - O-arylation - metal-free reactions - 1,4-oxathiines

Publication History

Received: 27 January 2021

Accepted after revision: 10 February 2021

Accepted Manuscript online:
10 February 2021

Article published online:
30 March 2021

• References and Notes

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• 13 3-Fluoro-2-phenylbenzo[b][1,4]oxathiine 4,4-dioxide (2a); Typical Procedure Substrate 1a (0.2 mmol, 1.0 equiv), tetramethylguanidine (TMG, 0.01 mmol, 100 μL of 0.1 M TMG in DMF), and 3 Å molecular sieves (100 mg, 3 Å molecular sieves were activated at 180 °C for 5 h) were mixed in anhydrous DMF (1.0 mL) at 80 °C for 10 h. After the reaction was complete, the solvent was evaporated and the crude mixture was purified by flash chromatography on silica gel (PE/EtOAc/DCM = 12:1:1) to afford the desired compound 2a in 90% yield; white solid; mp 131–133 °C. ¹H NMR (400 MHz, chloroform-d): δ = 8.04–7.97 (m, 1 H), 7.80 (dd, J = 6.7, 2.9 Hz, 2 H), 7.72–7.64 (m, 1 H), 7.53 (dd, J = 5.0, 1.9 Hz, 3 H), 7.48–7.38 (m, 2 H). ¹³C NMR (100 MHz, chloroform-d): δ = 150.0, 144.4 (d, J = 21.1 Hz), 141.6 (d, J = 276.7 Hz), 134.2, 131.6, 128.9, 128.0, 127.9, 126.2 (d, J = 6.2 Hz), 125.6, 123.2 (d, J = 2.6 Hz), 119.2. ¹⁹F NMR (376 MHz, chloroform-d): δ = –175.89. HRMS (ESI): m/z calcd for C₁₄H₉FNaO₃S [M + Na]⁺: 299.0149; found: 299.0145.