Synthesis of Vinylsulfone Derivatives of Sugars: An Easy Preparation of (2R,3S,4E)-5-Benzenesulfonyl-2,3-iso-propylidene-dioxy-pent-4-en-1-yl-tosylate

Abstract

A two-step procedure for the synthesis of (2R,3S,4E)-5-benzenesulfonyl-2,3-isopropylidene-dioxypent-4-en-1-yl-tosylate is described. The method involves the addition of lithio(phenylsulfonyl)methane to 2,3-O-iso-propylidene-d-erythronolactol and treatment of the resulting diols with tosyl chloride.

Key words

stereoselectivity - vinyl sulfones - aminosugars - 2,3-O-isopropylidene-d-erythronolactol

References

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11

To a solution of PhSO₂Me (4.10 g, 26.3 mmol) in dry THF (40 mL), was added drop wise a solution 1.6 M of n-BuLi (16.4 mL, 26.3 mmol) at 0 °C and stirred under argon for 10 min, cooled down to -78 °C and cannulated to a solution of lactol 6 (2.80 g, 17.5 mmol) in 60 mL of THF. After 30 min the cooling bath was removed and stirring was continued at r.t. for 2 h, quenched with sat. NH₄Cl solution and extracted with EtOAc. The combined organic layers were washed with water and brine and dried over Na₂SO₄. After concentration the residue was purified by chromatography (n-hexane/EtOAc: 7/3) to give a mixture (75/25) of 7 and 8 [12] (5.3 g, 95%). This mixture of 7 and 8 (5.3 g, 16.8 mmol) was added to a solution of THF washed NaH (2.7 g, 67.1 mmol) in dry THF (20 mL) at 0 °C and stirred at that temperature for 40 min, cooling down to -78 °C and then added a mixture of TsCl (19.2 g, 100.6 mmol) in dry THF (30 mL). The mixture was stirred for 15 min, quenched with 2 N HCl until neutral pH and extracted with EtOAc. The combined organic layers were washed with H₂O and brine and dried over Na₂SO₄. After concentration the residue was purified by chromatography (n-hexane/EtOAc: 8/2) to give a mixture of olefins 3 (5.1 g, 68%) and 11 (1.7 g, 22%) and tetrahydrofurans 9 (150 mg, 3%), and 10 (100 mg, 2%). Spectroscopic data for compounds 3, 9 and 10, see ref. [3] . Spectroscopic data for compound 11: [α] _d ²⁰ = +184.0 (c 1.30, CHCl₃). IR (film): ν = 1456, 1364, 1308, 1177, 988 cm^-1. ¹H NMR (CDCl₃, 200 MHz): δ = 7.95-7.31 (9 H, m,
-Ar), 6.34-6.20 (2 H, m, H-4, H-5), 5.72 (1 H, dd, J = 5.4 and 7.4 Hz, H-3), 4.62 (1 H, ddd, J = 3.8, 4.8 and 7.4 Hz, H-2), 4.11 (1 H, dd, J = 3.8 and 10.6 Hz, H_A-5), 3.94 (1 H, dd, J = 4.8 and 10.6 Hz, H_B-1), 2.44 (3 H, s, CH₃-Ts), 1.44 (CH₃-acetonide), 1.36 (CH₃-acetonide). ¹³C NMR (CDCl₃, 50.3 MHz): δ = 145.2 (C-ipso, -Ts), 141.5 (CH-4), 140.1 (C-ipso, -SO₂Ph), 134.3 (CH-5), 132.8 (C-ipso, -Ts), 132.1 (CH-para, -SO₂Ph), 130.1 (2 CH-meta, -Ts), 129.8 (2 CH-ortho, -Ts), 128.2 (2 CH-meta, -SO₂Ph), 127.7 (2 CH-ortho,
-SO₂Ph), 110.5 (C-acetonide), 76.5 (CH-3), 72.8 (CH-2), 68.4 (CH₂-5), 27.3 (CH₃-acetonide), 25.2 (CH₃-acetonide), 21.9 (CH₃-Ts). MS (EI): m/z (%) = 452 (5) [M⁺], 437(25), 267 (10), 238 (20), 209 (30), 155 (50), 125 (60), 91 (100). HRMS (EI): m/z calcd for C₂₁H₂₄O₇S₂: 452.0963. Found: 452.0964.

12

These compounds could be separated by careful chromatography in (n-hexane/EtOAc: 7/3). Spectroscopic data for compound 7: [α] _d ²⁰ = -58.3º (c 0.90, CHCl₃). IR (film): ν = 3500, 1306, 1142, 1071, 855 cm^-1. ¹H NMR (CDCl₃, 200 MHz): δ = 7.95-7.40 (5 H, m, -Ar), 4.36-4.19 (2 H, m, H-2 and H-3), 3.95-3.74 (3 H, m, H-4, 2 H-1), 3.59 (1 H, d, J = 14.4 Hz, H_A-5), 3.19 (1 H, dd, J = 10.0 and 14.4 Hz, H_B-5), 1.26 (3 H, s, Me), 1.41 (3 H, s, Me), ¹³C NMR (CDCl₃, 50.3 MHz): δ = 139.5 (C-ipso), 134.2 (CH-para), 129.6 (2CH-meta), 128.2 (2 CH-ortho), 109.0 (C-acetonide), 78.0 (CH-2), 77.4 (CH-3), 65.4 (CH-4), 60.4 (CH₂-1), 59.7 (CH₂-5), 27.7 (CH₃-acetonide), 25.4 (CH₃-acetonide). Spectroscopic data for compound 8: [α] _d ²⁰ =
-14.2 (c 1.21, CHCl₃). IR (film): ν 3500, 1449, 1304, 1217, 1146 cm^-1. ¹H NMR (CDCl₃, 200 MHz): δ = 7.95-7.40 (5 H, m, -Ar), 4.37 (1 H, ddd, J = 2.6, 3.6 and 7.8 Hz, H-4), 4.23 (1 H, m, H-2), 4.12 (1 H, dd, J = 2.2 and 6.6 Hz, H-3), 3.83 (2 H, t, J = 4.0 Hz, H-1), 3.42 (1 H, dd, J = 8.2 and 14.4 Hz, H_A-5), 3.30 (1 H, dd, J = 3.6 and 14.4 Hz, H_B-5), 1.48 (3 H, s, Me), 1.34 (3 H, s, Me). ¹³C NMR (CDCl₃, 50.3 MHz): δ = 139.9 (C-ipso), 134.1 (CH-para), 129.5 (2 CH-meta), 128.2 (2 CH-ortho), 108.9 (C-acetonide), 78.8 (CH-2), 77.2 (CH-3), 65.0 (CH-4), 60.5 (CH₂-1), 60.4 (CH₂-5), 26.9 (CH₃-acetonide), 25.1 (CH₃-acetonide).