A Novel Three-Component Reaction Involving Terminal Alkynes, Elemental Sulfur, and Strained Heterocycles

Abstract

An efficient one-pot procedure to synthesize 1,3-oxathiolane-2-alkylidene and 1,3-thiazolidine-2-alkylidene structures is described. Anionic adducts derived from terminal alkynes and elemental sulfur attack strained heterocycles regioselectively to afford the corresponding heterocyclic compounds.

Key words

alkynes - epoxides - heterocycles - multicomponent reaction - sulfur - ring opening

• References and Notes

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• 22 Typical Procedure for the Preparation of 5 and 6 A mixture of NaH (60%w/w in paraffin, 40 mg) in DMF (3 mL) was treated dropwise over 10 min with a solution of the requisite terminal alkyne 1 (1 mmol) in THF (2 mL) at –10 °C. After 30 min elemental sulfur (1.1 mmol) was added, and the mixture was allowed to warm to r.t. Then, 3 or 4 (1 mmol) was added, and the resulting yellow mixture was stirred for 16–22 h at 50 °C. The mixture was quenched with sat. NH₄Cl (10 mL) and allowed to stir for 30 min, followed by extraction with CH₂Cl₂ (3 × 6 mL). The combined organic extracts were dried (Na₂SO₄), filtered, and concentrated under reduced pressure. The residue was purified by chromatography (silica gel; hexane–EtOAc, 4:1) to give the desired product. 2-Benzylidene-5-methyl-1,3-oxathiolane (5a) Pale yellow oil; yield = 0.17 g (89%). IR (KBr): ν_max = 3025, 2967, 1610, 1543, 1326, 1121 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 1.28 (3 H, d, ³ J = 7.2 Hz, Me), 3.26 (H, dd, ² J = 11.9 Hz, ³ J = 7.1 Hz, CH), 3.41 (H, dd, ² J = 11.9 Hz, ³ J = 4.9 Hz, CH), 4.82–4.86 (H, m, CH), 5.18 (H, s, CH), 7.12 (H, t, ³ J = 6.9 Hz), 7.20 (2 H, t, ³ J = 6.8 Hz), 7.28 (2 H, d, ³ J = 6.6 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 19.4 (Me), 41.5 (CH₂), 78.1 (CH), 123.4 (2 CH), 126.4 (CH), 129.1 (2 CH), 131.7 (CH), 136.3 (C), 163.3 (C). MS: m/z (%) = 192 (2) [M⁺], 157 (67), 151 (84), 118 (74), 101 (45), 91 (32), 77 (100), 58 (37). Anal. Calcd for C₁₁H₁₂OS (192.28): C, 68.71; H, 6.29; S, 16.68. Found: C, 68.86; H, 6.35; S, 16.73. 2-Benzylidene-5-methyl-5-propyl-1,3-oxathiolane (5b) Pale yellow oil; yield = 0.19 g (83%). IR (KBr): ν_max = 3021, 3010, 2945, 1634, 1536, 1325, 1130 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 0.92 (3 H, t, ³ J = 6.2 Hz, Me), 1.32-1.37 (2 H, m,CH₂), 1.39 (3 H, s, Me), 1.51 (2 H, t, ³ J = 6.4 Hz, CH₂), 3.29 (H, d, ² J = 11.6 Hz, CH), 3.48 (H, d, ² J = 11.6 Hz, CH), 5.16 (H, s, CH), 7.13 (H, t, ³ J = 6.7 Hz), 7.23 (2 H, t, ³ J = 6.7 Hz), 7.31 (2 H, d, ³ J = 6.4 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.0 (CH₂), 14.3 (Me), 23.1 (Me), 39.2 (CH₂), 43.1 (CH₂), 89.5 (C), 122.1 (2 CH), 125.8 (CH), 130.3 (2 CH), 131.5 (CH), 136.2 (C), 162.9 (C). MS: m/z (%) = 234 (1) [M⁺], 217 (47), 151 (81), 144 (78), 135 (69), 101 (52), 91 (37), 77 (100), 83 (58). Anal. Calcd for C₁₄H₁₈OS (234.36): C, 71.75; H, 7.74; S, 13.68. Found: C, 71.86; H, 7.89; S, 13.69. 2-Benzylidene-5-phenyl-3-tosylthiazolidine (6a) Pale yellow solid, mp 103–104.5 °C; yield = 0.32 g (78%). IR (KBr): ν_max = 3034, 3022, 2957, 1641, 1527, 1512, 1330, 1243, 1137 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 2.23 (3 H, s, Me), 4.29 (H, m, CH), 4.65 (H, dd, ² J = 11.8 Hz, ³ J = 4.7 Hz, CH), 4.73 (H, dd, ² J = 11.8 Hz, ³ J = 4.7 Hz, CH), 5.08 (H, s, CH), 7.10–7.31 (10 H, m), 7.35 (2 H, d, ³ J = 6.7 Hz), 7.81 (2 H, d, ³ J = 6.6 Hz). ¹³C NMR (125.7 MHz, CDCl₃): δ = 23.2 (Me), 42.1 (CH₂), 69.4 (CH), 113.3 (CH), 125.3 (2 CH), 126.5 (2 CH), 127.0 (CH), 127.4 (2 CH), 128.0 (CH), 128.5 (2 CH), 129.1 (2 CH), 130.5 (2 CH), 136.7 (C), 137.0 (C), 140.2 (C), 143.9 (C), 155.3 (C). MS: m/z (%) = 407 (1) [M⁺], 375 (37), 304 (85), 272 (61), 220 (80), 155 (73), 103 (41), 77 (100). Anal. Calcd for C₂₃H₂₁NO₂S₂ (407.55): C, 67.78; H, 5.19; N, 3.44; S, 15.74. Found: C, 67.89; H, 5.30; N, 3.52; S, 15.78. 4-Benzyl-2-butylidene-3-tosylthiazolidine (6b) Pale yellow solid, mp 89–91 °C; yield = 0.27 g (69%). IR (KBr): ν_max = 3047, 3021, 2952, 1647, 1527, 1510, 1326, 1310, 1236, 1127 cm^–1. ¹H NMR (500.1 MHz, CDCl₃): δ = 0.91 (3 H, t, ³ J = 6.1 Hz, Me), 1.29–1.34 (2 H, m, CH₂), 2.11–2.14 (2 H, m, CH₂), 2.25 (3 H, s, Me), 3.21 (H, dd, ² J = 11.9 Hz, ³ J = 7.1 Hz, CH), 3.32 (H, dd, ² J = 11.9 Hz, ³ J = 4.9 Hz, CH), 3.53 (2 H, m, CH₂), 4.59 (H, t, ³ J = 6.3 Hz, CH), 5.13–5.19 (H, m, CH), 7.11–7.29 (5 H, m), 7.36 (2 H, d, ³ J = 6.4 Hz, 2 CH), 7.82 (2 H, d, ³ J = 6.5 Hz, 2 CH). ¹³C NMR (125.7 MHz, CDCl₃): δ = 13.2 (Me), 23.2 (CH₂), 24.2 (Me), 27.2 (CH₂), 42.7 (CH₂), 47.0 (CH₂), 68.9 (CH), 108.4 (CH), 126.1 (CH), 127.4 (2 CH), 129.1 (2 CH), 129.8 (2 CH), 131.4 (2 CH), 135.9 (C), 139.1 (C), 143.0 (C), 157.2 (C). MS: m/z (%) = 387 (1) [M⁺], 354 (40), 270 (86), 238 (72), 200 (68), 155 (59), 117 (53), 77 (100). Anal. Calcd for C₂₁H₂₅NO₂S₂ (387.56): C, 65.08; H, 6.50; N, 3.61; S, 16.55. Found: C, 65.19; H, 6.64; N, 3.70; S, 16.62.