Asymmetric Oxidopyrylium-Alkene [5+2] Cycloaddition: Synthesis of Enantiopure oxa-Bridged Bicyclo[5.4.0]undecanes

Abstract

A facile route to the synthesis of enantiomeric oxa-bridged bicycloadducts 9 and 18 has been developed employing an intramolecular [5+2] cycloaddition of 3-oxidopyrylium with unsaturated sugars.

d-ribose - furyl lithium - 3-oxidopyrylium - [5+2] cycloaddition

References

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<A NAME="RG22003ST-6">6</A>

Experimental Procedure for the Synthesis of Cycloadducts 9 and 10: To a solution of pyranone acetate 8 (0.038 g, 0.09 mmol) in CH₃CN (0.5 mL) was added Et₃N (0.05 mL, 4 equiv.) at r.t. The reaction mixture was heated at reflux for 20 h. After being cooled to 25 °C, the solvent was evaporated under reduced pressure and the residue was purified by flash chromatography to afford the cycloadduct 9 and 10 as 93:7 inseparable mixtures of diastereomers (0.021 g, 65%). [α]_D ²⁵ +38.5 (c 0.91, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.43-7.28 (m, 5 H), 7.25 (dd, J = 9.6, 4.4 Hz, 1 H), 5.94 (d, J = 9.6 Hz, 1 H), 5.0 (d, J = 6.8 Hz, 1 H), 4.94 (m, 1 H), 4.70 (d, J = 12 Hz, AB system, 1 H), 4.59 (d, J = 12.4 Hz, AB system, 1 H), 4.65 (m, 1 H), 3.40 (m, 1 H), 1.99-1.71 (m, 5 H), 1.42 (s, 3 H), 1.25 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 197.0, 152.3, 138.0, 128.3, 127.6, 127.5, 125.5, 109.6, 84.1, 75.1, 72.9, 72.6, 70.6, 38.5, 35.5, 28.2, 26.3, 24.9. HRMS calcd for C₂₁H₂₄O₅: 356.1624 (M⁺). Found: 356.1628.

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<A NAME="RG22003ST-9">9</A>

Experimental Procedure for the Synthesis of Cycloadduct 18: To a solution of pyranone acetate 17 (0.1g, 0.27 mmol) in CH₃CN (1.5 mL) was added Et₃N (0.15 mL) at r.t. The reaction mixture was heated at reflux for 6 h. after being cooled to 25 °C, the solvent was evaporated under reduced pressure and the residue was purified by flash chromatography to afford the cycloadduct 18 (0.70 g, 83%). Mp 148-150 °C, [α]_D ²⁵ -183.3 (c 0.42, CHCl₃). ¹H NMR (400 MHz, CDCl₃): δ = 7.22 (dd, J = 9.6, 4 Hz, 1 H), 5.97 (d, J = 9.6 Hz, 1 H), 5.0 (m, J = 6.4, 3.2 Hz, 1 H), 4.93 (dd, J = 4.8, 4 Hz, 1 H), 4.64 (m, 2 H), 2.20-1.87 (m, 5 H), 2.1 (s, 3 H), 1.56 (s, 3 H), 1.40 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 196.3, 170.0, 151.9, 125.3, 109.5, 83.7, 72.9, 72.8, 72.0, 70.6, 37.8, 35.3, 27.8, 26.2, 24.9, 21.1. HRMS calcd for C₁₆H₂₀O₆: 308.1260 (M⁺). Found: 308.1271.

<A NAME="RG22003ST-10">10</A>

Crystal Data of 18: C₁₆H₂₀O₆, M = 308.32, crystal size 0.30 × 0.30 × 0.15 mm, monoclinic, a = 9.5590 (6), b = 8.8780 (9), c = 10.2790(7) Å, U = 796.40 (11) ų, T = 293 (2) K, space group P21, Z = 2, m = 0.098 mm^-1, 1311 reflections measured, 1311 unique (R _int = 0.0000). The final R indices [I>2σ (I)] R1 = 0.0404, wR2 = 0.0880, R indices (all data) R1 = 0.0586, wR2 = 0.1058. Details of the crystal structure determination (deposition number CCDC 212708) may be obtained free of charge on application to CCDC, 12 Union Road, Cambridge CB21EZ, UK [Fax: [phone]; E-mail: [e-mail]].