Ozonolytic Cleavage of 3-Oxidopyrilium Betaine-Derived Cycloadducts: Simple and Efficient Access to Stereodefined Tetrahydrofurans

Abstract

A range of bicyclic allylic alcohols, obtained from the highly stereoselective reduction of endo-adducts derived from [3+2] cycloaddition of 3-oxidopyrilium betaine to various olefins, undergo efficient ozonolytic cleavage followed by reduction to yield stereodefined tetrahydrofurans in high overall yields as single diastereoisomers.

Key words

cycloaddition - stereoselective - cleavage - ozonolysis - stereocontrol

References

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• 8 In a typical procedure, to a stirred solution of acetate 5 (R = Ph) (247 mg, 1 mmol) in MeOH (10 mL) was added a stream of ozone gas until the solution was seen to develop a slight blue colouration. After completely saturating the solution, firstly with oxygen gas and then with nitrogen gas, the solvent was carefully removed in vacuo and replaced with anhyd THF (10 mL). This solution was then added to a slurry of lithium aluminium hydride (231 mg, 6.07 mmol) in anhyd THF and the resulting mixture was stirred under nitrogen for 16 h. Following the dropwise addition of a mixture of EtOAc and MeOH (1:1, 10 mL), and evaporation in vacuo. Acetic anhydride (5 mL) and anhyd pyridine (3 mL) were added and the resulting solution stirred for 16 h. Following removal of the solvents in vacuo, chromato-graphy of the residue on silica (EtOAc-petrol ether, 4:6) gave triacetate 6 (R = Ph) as a colourless oil (277 mg, 62%); IR: ν_max = 3029, 2955, 2888, 1743 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 1.94 (3 H, s, Ac), 2.08 (3 H, s, Ac), 2.09 (1 H, m, H-3), 2.17 (3 H, s, Ac), 2.35 (1 H, m, H-3), 3.65-3.80 (3 H, m, H-4, H-6), 4.21-4.48 (4 H, m, H-2, H-5, H-8), 5.27 (1 H, m, H-7), 7.22-7.34 (5 H, m, PhH). Anal. Calcd for C₁₉H₂₄O₇ (%): C, 62.64; H, 6.59. Found: C, 62.85; H, 6.65. MS (EI): m/z (%) = 365 (0.7) [M⁺ + 1], 304 (16) [M⁺ - HOAc], 219 (50) [M⁺ - C₂H₂Oac], 159 (43) [219 - HOAc]

6

Only one stereoisomer could be detected in the ¹H NMR spectra of the crude reaction mixtures.