Water-Promoted Highly Selective Anti-Markovnikov Addition of Thiols to Unactivated Alkenes

Abstract

The highly selective anti-Markovnikov addition of thiols to unactivated alkenes is demonstrated in water at room temperature without any additive. This is a very simple and efficient method for the synthesis of linear thioethers.

Key words

water - anti-Markovnikov addition - thiol - thioether - ­unactivated alkene

References and Notes

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10

Typical Experimental Procedure (Table 1, entry 14): A mixture of styrene (1 mmol, 104 mg) and thiophenol (1.1 mmol, 121 mg) was stirred in H₂O (0.5 mL) at r.t. for 1.5 h until completion of the reaction (monitored by TLC). The reaction mixture was extracted with Et₂O (3 × 10 mL). The Et₂O extract was washed with H₂O, NaOH solution (2%) and then brine and dried over Na₂SO₄. Evaporation of the solvent gave a crude product which was purified by column chromatography over silica gel (hexane-Et₂O, 95:5) to provide 2-phenylsulfanylethylbenzene (192.6 mg, 90%) as a colorless liquid. This procedure was followed for all the reactions listed in Table [1] .

15

Table 1, entry 7: Yellow oil. IR (neat): 1590, 2957 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.79-1.83 (m, 2 H), 1.95-2.02 (m, 2 H), 3.53-3.60 (m, 1 H), 4.10-4.17 (m, 1 H), 5.14-5.17 (m, 1 H), 7.21-7.52 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 24.6, 32.4, 67.1, 87.0, 128.7 (2 C), 132.2 (2 C), 132.7, 134.1. Anal. Calcd for C₁₀H₁₁ClOS: C, 55.94; H, 5.16. Found: C, 55.73; H, 5.18.

18

Table 1, entry 10: Yellow viscous liquid. IR (neat): 1741, 1477, 1382 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.00 (s, 3 H), 3.09 (t, J = 6.9 Hz, 2 H), 4.20 (t, J = 6.9 Hz, 2 H), 7.23-7.32 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 20.8, 32.6, 62.7, 129.3 (2 C), 131.2 (2 C), 132.7, 133.7, 170.8. Anal. Calcd for C₁₀H₁₁ClO₂S: C, 52.06; H, 4.81. Found: C, 51.78; H, 4.72.

19

Table 1, entry 11: Yellow viscous liquid. IR (neat): 1735, 2933, 2979 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.30 (d, J = 2.4 Hz, 3 H), 1.95 (s, 3 H), 2.88-2.95 (m, 1 H), 3.07-3.14 (m, 1 H), 4.96-5.02 (m, 1 H), 7.21-7.31 (m, 4 H). ¹³C NMR (75 MHz, CDCl₃): δ = 19.2, 21.1, 39.3, 69.5, 129.1 (2 C), 131.0 (2 C), 132.4, 134.4, 170.4. Anal. Calcd for C₁₁H₁₃ClO₂S: C, 53.98; H, 5.35. Found: C, 53.76; H, 5.23.

20

Table 1, entry 13: Colorless liquid. IR (neat): 1479, 1585, 2925 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.76-1.94 (m, 2 H), 2.48-2.67 (t, J = 7.12 Hz, 4 H), 2.76-2.86 (m, 4 H), 2.88-2.94 (m, 4 H), 7.14-7.38 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 29.3, 31.1 (2 C), 33.7 (2 C), 36.9 (2 C), 126.4 (4 C), 128.4 (4 C), 130.6 (2 C), 140.6 (2 C). Anal. Calcd for C₁₉H₂₄S₂: C, 72.10; H, 7.64. Found: C, 72.29; H, 7.58.

21

Table 1, entry 15: Colorless liquid. IR (neat): 1580, 2934 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.93 (t, J = 6.9 Hz, 2 H), 3.16 (t, J = 6.9 Hz, 2 H), 7.20-7.35 (m, 9 H). ¹³C NMR (75 MHz, CDCl₃): δ = 35.2, 35.6, 126.6 (2 C), 127.8 (2 C), 128.5 (2 C), 129.0 (2 C), 130.6, 132.0, 135.0, 140.0. Anal. Calcd for C₁₄H₁₃ClS: C, 67.59; H, 5.27. Found: C, 67.86; H, 5.16.

25

Table 1, entry 23: Yellow oil. IR (neat): 1246, 1489, 1588 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 2.83 (t, J = 7.2 Hz, 2 H), 3.10 (t, J = 7.2 Hz, 2 H), 5.95 (s, 2 H), 6.61-6.75 (m, 4 H), 7.12-7.26 (m, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 35.3, 35.7, 101.3, 108.3, 109.0, 121.6, 129.1, 129.4 (2 C), 130.7 (2 C), 133.8, 134.9, 146.2, 147.8. Anal. Calcd for C₁₅H₁₃O₂SCl: C, 61.53; H, 4.48. Found: C, 61.49; H, 4.34.