Manganese(III)-Mediated Radical Reactions in Carbohydrate Chemistry: A New Route to 3-Deoxy-d-manno-oct-2-ulosonic Acid (KDO)

Abstract

An acyclic alkene derived from a carbohydrate is employed as a substrate for manganese-mediated radical reactions for the first time. The addition of malonate is interesting for the mechanism of such reactions, whereas acetic acid as radical precursor affords lactones in excellent yield. The main diastereomer was easily separated and represents a key intermediate in the synthesis of KDO.

Key words

carbohydrates - lactones - natural products - radical reactions - transition metals

References

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12

A solution of 632 mg (2.00 mmol) of alkene 2 and 1.00 g of potassium acetate in 10 mL of HOAc was heated to 90 °C under argon atmosphere. After the addition of 2.14 g (8.00 mmol, 4.0 equiv) of manganese(III) acetate dihydrate, the solution was stirred at this temperature for 60 h. The mixture was diluted with 300 mL of ice water, extracted with 8 × 50 mL of CH₂Cl₂ and the combined organic phases were washed with 100 mL of a diluted solution of Na₂S₂O₃ and 4 × 50 mL of a solution of NaHCO₃ and dried over Na₂SO₄. The solvent was removed at 35 °C and the residue was purified by silica gel column chromatography (CH₂Cl₂-EtOAc 90:10) to afford 455 mg (61%) of manno-5 (R _f = 0.27) as a white solid, mp 129-130 °C (recrystalliza-tion from EtOH) and 220 mg (29%) of gluco-5 (R _f = 0.22) as a colorless oil. Lactone manno-5: [α]_D ²⁵ +10.5 (c 1.01, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 2.07, 2.08, 2.12, 2.14 (4 s, each 3 H, OAc), 2.17 (dddd, J = 13.2, 9.8, 9.0, 7.4 Hz, 1 H, 3-H), 2.24 (dddd, J = 13.2, 9.0, 7.4, 5.5 Hz, 1 H, 3′-H), 2.51 (dt, J = 17.9, 9.0 Hz, 1 H, 2-H), 2.57 (ddd, J = 17.9, 9.8, 5.5 Hz, 1 H, 2′-H), 4.13 (dd, J = 12.5, 4.8 Hz, 1 H, 8-H), 4.26 (dd, J = 12.5, 2.7 Hz, 1 H, 8′-H), 4.57 (dt, J = 7.4, 6.1 Hz, 1 H, 4-H), 5.08 (ddd, J = 8.7, 4.8, 2.7 Hz, 1 H, 7-H), 5.33 (dd, J = 6.1, 2.5 Hz, 1 H, 5-H), 5.51 (dd, J = 8.7, 2.5 Hz, 1 H, 6-H). ¹³C NMR (125 MHz, CDCl₃): δ = 20.6, 20.7, 20.8, 20.9 (4 q, OAc), 23.4 (t, C-3), 27.7 (t, C-2), 61.5 (t, C-8), 68.0, 68.1, 69.9 (3 d, C-5, C-6, C-7), 77.2 (d, C-4), 169.5, 169.9, 170.0, 170.6 (4 s, OAc), 176.1 (s, C-1). Anal. Calcd for C₁₆H₂₂O₁₀: C, 51.34; H, 5.92. Found: C, 51.18; H, 5.84. Lactone gluco-5: [α]_D ²⁵ +36.0 (c 1.15, CHCl₃). ¹H NMR (500 MHz, CDCl₃): δ = 2.01 (dddd, J = 13.2, 9.1, 8.9, 7.2 Hz, 1 H, 3-H), 2.04, 2.06, 2.11, 2.14 (4 s, each 3 H, OAc), 2.34-2.42 (m, 1 H, 3′-H), 2.46-2.50 (m, 2 H, 2-H), 4.14 (dd, J = 12.6, 4.3 Hz, 1 H, 8-H), 4.22 (dd, J = 12.6, 2.5 Hz, 1 H, 8′-H), 4.57 (td, J = 7.2, 5.5 Hz, 1 H, 4-H), 5.10 (ddd, J = 9.1, 4.3, 2.5 Hz, 1 H, 7-H), 5.25 (dd, J = 5.5, 2.2 Hz, 1 H, 5-H), 5.42 (dd, J = 9.1, 2.2 Hz, 1 H, 6-H). ¹³C NMR (125 MHz, CDCl₃): δ = 20.6, 20.7, 20.8, 20.9 (4 q, OAc), 24.4 (t, C-3), 27.7 (t, C-2), 61.4 (t, C-8), 67.8, 68.2, 70.6 (3 d, C-5, C-6, C-7), 78.4 (d, C-4), 169.7, 170.1, 170.2, 170.5 (4 s, OAc), 175.7 (s, C-1). Anal. Calcd for C₁₆H₂₂O₁₀: C, 51.34; H, 5.92. Found: C, 51.37; H, 5.72.