Indium(I) Iodide-Promoted Cleavage of Dialkyl Disulfides and Subsequent Michael Addition of Thiolate Anions to Conjugated Carbonyl Compounds

Abstract

Indium(I) iodide promotes cleavage of dialkyl disulfides generating thiolate anions which then undergo facile addition to α,β-unsaturated ketones, aldehydes, carboxylic esters and nitriles under neutral conditions producing corresponding β-keto or β-cyano sulfides in high yields. There are several examples of dialkyl/diaryl disulfides and activated alkenes participating in this reaction.

indium(I) iodide - dialkyl disulfide - Michael addition - β-keto sulfide - β-cyano sulfide

References

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6

General Experimental Procedure; Representative Example for the Cleavage of Diphenyl Disulfide and Subsequent Reaction with Methyl Vinyl Ketone (Entry 2): Indium(I) iodide (121 mg, 0.5 mmol) was added to the solution of diphenyl disulfide (109 mg, 0.5 mmol) in freshly distilled THF (2.5 mL) under argon atmosphere followed by the addition of methyl vinyl ketone (70 mg, 1 mmol). The reaction mixture was heated under reflux for 2.5 h (TLC). THF was then evaporated off and the residue was quenched with water and extracted with Et₂O (3 × 10 mL). The Et₂O extract was washed with water and dried (Na₂SO₄). The aqueous extract containing indium derivatives was discarded although in relatively large-scale reactions indium salts may be recovered. Evaporation of the solvent left the crude product, which was purified by column chromatography over silica gel (hexane-Et₂O, 95:5) to provide the pure addition product, 4-thiophenylbutan-2-one (155 mg, 86%) as a colorless liquid. IR (neat): 1716, 1477 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.14 (s, 3 H), 2.76 (t, J = 7.26 Hz, 2 H), 3.13 (t, J = 7.26 Hz, 2 H), 7.20-7.22 (m, 2 H), 7.26-7.35 (m, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 27.9, 30.5, 43.5, 126.7, 127.9, 129.4 (2 × C), 130.0 (2 × C). These values are in good agreement with those reported for this compound.⁹ Several Michael adducts are known and are identified by comparison of their spectroscopic data with those reported. The new compounds are characterized by their spectroscopic data and elemental analysis. These data for a few selective representative compounds are provided here.
Entry 8: IR (neat): 1475, 1716 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.27 (d, J = 6.51 Hz, 3 H), 2.12 (s, 3 H), 2.55 (dd, J ₁ = 8.34 Hz, J ₂ = 17.22 Hz, 1 H), 2.72 (dd, J ₁ = 5.31 Hz, J ₂ = 17.19 Hz, 1 H), 3.65 (m, 1 H), 7.26 (d, J = 8.61 Hz, 2 H), 7.33 (d, J = 8.61 Hz, 2 H). ¹³C NMR (75 MHz): δ = 20.9, 30.5, 38.4, 50.0, 129.0 (2 × C), 132.5, 133.4, 133.6 (2 × C), 206.2. Anal. Calcd for C₁₁H₁₃OClS: C, 57.76; H, 5.73. Found: C, 57.84; H, 5.81.
Entry 17: IR (neat): 1477, 1724 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.33 (d, J = 6.75 Hz, 3 H), 2.55-2.61 (m, 2 H), 3.13-3.19 (m, 1 H), 3.78 (s, 2 H), 7.24-7.33 (m, 5 H), 9.66 (s, 1 H). ¹³C NMR (75 MHz): δ = 21.3, 33.6, 35.2, 50.1, 127.1, 128.5 (2 × C), 128.7 (2 × C), 137.9, 200.5. Anal. Calcd for C₁₁H₁₄OS: C, 68.0; H, 7.26. Found: C, 68.09; H, 7.17.
Entry 20: Obtained as a mixture of diastereoisomers (59:41). IR (neat): 1475, 1724, 2721 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.04 (t, J = 7.17 Hz, 3 H), 1.20 (d, J = 7.21 Hz, 3 H), 1.62-1.73 (m, 2 H), 2.63-2.67 (m, 1 H), 3.34-3.40 (m, 1 H), 7.26 (d, J = 8.34 Hz, 2 H), 7.37 (d, J = 8.34 Hz, 2 H), 9.67 (d, J = 1.59 Hz, 1 H, minor), 9.68 (d, J = 0.98 Hz, 1 H, major). ¹³C NMR (75 MHz): δ = 9.7 (major), 10.2 (minor), 12.1 (major), 11.8 (minor), 26.2 (major), 24.2 (minor), 48.9 (major), 49.6 (minor), 52.9 (major), 51.7 (minor), 129.1 (2 × C), 133.4, 133.5 (2 × C), 133.6, 203.2. Anal. Calcd for C₁₂H₁₅OClS: C, 59.37; H, 6.23. Found: C, 59.41; H, 6.17.
Entry 24: IR (neat): 1477, 1737 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.59 (t, J = 7.5 Hz, 2 H), 3.13 (t, J = 7.5 Hz, 2 H), 3.67 (s, 3 H), 7.19-7.29 (m, 4 H). ¹³C NMR (75 MHz): δ = 29.7, 34.4, 52.3, 129.5 (2 × C), 131.8 (2 × C), 134.1, 134.2, 172.4. Anal. Calcd for C₁₀H₁₁O₂ClS: C, 52.06; H, 4.77. Found: C, 52.11; H, 4.71.

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