One-Pot Practical Preparation of Novel Propargylic Aryl and Heteroaryl Sulfides and Sulfones

Abstract

A one-pot preparation of functionalized propargylic aryl and hetero aryl sulfides from primary alcohols and thiols through the formation of the corresponding iodide or tosylate compounds is presented. The corresponding sulfones are prepared by subsequent MCPBA oxidation.

Key words

thiols - sulfides - sulfones - oxidation - propargylic alcohol

References

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13

The corresponding iodide was isolated in minor yield (70% vs. 79%) with respect to the tosylate.

14

General Procedure for Preparation of Sulfides 4a-c, 4g-i (Method A). To a stirred solution of propargyl alcohol 1a,c (1 equiv, 0.78 mmol) in CH₂Cl₂ (13 mL) were added PPh₃ (251 mg, 0.96 mmol), imidazole (158 mg, 2.32 mmol) and I₂ (237 mg, 0.94 mg). The reaction mixture was raised to reflux. After 1 h, a complete conversion of alcohol to the corresponding iodide was observed by TLC control. The reaction temperature was cooled to r.t. and thiol 3a-c (0.94 mmol) was added. After complete conversion to sulfide (3 h), the reaction mixture was hydrolyzed with a sat. aq solution of NH₄Cl. The organic layer was washed with brine, dried over Na₂SO₄ and concentrated in vacuo. The crude mixture was purified by column chromatography on silica gel.

15

General Procedure for Preparation of Sulfides 4d-f (Method B). To a stirred solution of propargylic alcohol 1b (202 mg, 1.01 mmol) in toluene (0.9 mL) at 0 °C Bu₄NI (39 mg, 0.10 mmol), 2 N solution of NaOH (1.5 mL), and a dropwise solution of TsCl (202 mg, 1.06 mmol) in toluene (0.4 mL) were added. The mixture was stirred for 3 h at r.t. and after the complete formation of the corresponding tosylate, thiol 3a-c (1.08 mmol) was added. After additional 2 h the aqueous layer was extracted with EtOAc, while the organic layer was washed with H₂O. The combined organic layers were dried over Na₂SO₄ and concentrated in vacuo. The crude mixture was purified by column chromatography on silica gel.

17

With our procedure the propargylic sulfides 4a and 4b have been prepared in higher yields than in the other older procedures reported in ref. 2, 3 and 10a.