Indium-Mediated Debromination of gem-Bromonitroalkanes under Mild Conditions in Aqueous Medium

Abstract

gem-Bromonitroalkanes are efficiently reduced into the corresponding dehalogenated products in excellent yields with indium metal in the presence of a palladium(0) catalyst and indium(III) chloride in aqueous medium. The addition of bromonitromethane to carbohydrate-derived aldehydes or imines, followed by debromination of the intermediate bromonitro compounds represents an extremely efficient method for the stereoselective preparation of nitrosugars.

Key words

reductive dehalogenation - indium - bromonitroalkanes - nitroalkanes - nitrosugars

• References

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• 20 Nitroalkanes 2; General Procedure NaI (0.12 mmol, 0.15 equiv) was added to a stirred solution of bromonitromethane (0.8 mmol, 1 equiv) and the corresponding aldehyde 3 (0.8 mmol, 1 equiv) in THF (10 mL), and the resulting mixture was stirred at r.t. for 5 h. After this period, the mixture was quenched with aq HCl (10 mL, 0.1 M) and extracted with Et₂O (1 × 20 mL). The combined extracts were washed with sat. aq Na₂S₂O₃ solution (1 × 20 mL), dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the crude 1-bromo-1-nitroalkan-2-ol. In metal (183 mg, 1.6 mmol), InCl₃ (88 mg, 0.4 mmol) and Pd(PPh₃)₄ (18 mg, 2 mol%) were added to a solution of the 1-bromo-1-nitroalkan-2-ol (0.8 mmol) in THF–H₂O (2:1, 6 mL). After stirring the mixture at r.t. for 12 h, it was quenched with HCl (3 mL, 1 M), diluted with H₂O (25 mL) and extracted with Et₂O (3 × 25 mL). The combined organic extracts were dried over Na₂SO₄, filtered and the solvent removed under reduced pressure to afford the nitroalkanes 2.
• 21 1-Cyclohexyl-2-nitroethanol (2a) Yellow oil; R_f  = 0.30 (hexane–EtOAc, 5:1). ¹H NMR (300 MHz, CDCl₃): δ = 4.45–4.33 (2 m, 3 H), 1.73–0.90 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 79.3, 72.8, 41.4, 27.9, 26.1, 25.9, 25.7, 22.8.
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• 23 N-(1-Cyclohexyl-2-nitroethyl)-4-methoxybenzenamine (2e) Brown oil; R_f  = 0.22 (hexane–EtOAc, 3:1). ¹H NMR (300 MHz, CDCl₃): δ = 6.76 (d, J = 9.0 Hz, 2 H), 6.65 (d, J = 9.0 Hz, 2 H), 4.72 (dd, J = 12.3, 5.2 Hz, 1 H), 4.46 (dd, J = 12.3, 7.4 Hz, 1 H), 4.08–4.04 (m, 1 H), 3.73 (s, 3 H), 2.73 (s, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 152.7 (C), 141.0 (C), 115.0 (2 × CH), 114.9 (2 × CH), 75.7 (CH₂), 60.9 (CH), 55.7 (CH₃), 43.0 (CH), 34.7 (2 × CH₂), 25.2 (CH₂), 21.6 (2 × CH₂). MS (ESI): m/z (%) = 279 (6) [M + H]⁺, 234 (19), 216 (100), 214 (28). HRMS (ESI): m/z [M + H]⁺ calcd for C₁₅H₂₃N₂O₃: 279.1709; found: 279.1703.
• 24 7-Deoxy-1,2:3,4-di-O-isopropylidene-7-nitro-d-glycero-β-d-galacto-heptopyranose (2g) Yellow oil; R_f  = 0.20 (hexane–EtOAc, 3:1); [α]_D ²⁰ –49.4 (c 0.6, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.49 (d, J = 5.0 Hz, 1 H), 4.78 (apparent d, J = 11.2 Hz, 1 H), 4.65 (dd, J = 8.0, 2.5 Hz, 1 H), 4.51–4.47 (m, 2 H), 4.43 (dd, J = 8.0, 2.0 Hz, 1 H), 4.34 (dd, J = 4.9, 2.5 Hz, 1 H), 3.73 (dd, J = 8.2, 2.0 Hz, 1 H), 2.89 (d, J = 5.9 Hz, 1 H), 1.51 (s, 3 H, CH ₃), 1.46 (s, 3 H, CH ₃), 1.37 (s, 3 H, CH ₃), 1.32 (s, 3 H, CH ₃). ¹³C NMR (75 MHz, CDCl₃): δ = 109.6, 108.9, 96.2, 78.1, 70.6, 70.5, 70.1, 67.7, 67.4, 25.9, 24.8, 24.3. MS (ESI): m/z (%) = 342 (24) [M + Na]⁺, 337 (100) [M + NH₄]⁺, 320 (19) [M + H]⁺, 262 (48).