Organolithium-Induced Synthesis of Unsaturated Diols from Epoxides of Dihydrofurans and Dihydropyrans; 4-(Trimethylsilyl)-3-methylenebutane-1,2-diol

Matthew Stent (matthew.stent@chem.ox.ac.uk),
A contribution from the Hodgson Group, Oxford

Chemicals Used
3,4-Epoxytetrahydrofuran (Tetrahedron, 1993, 49, 6263-6276) (Trimethylsilyl)methyllithium (1.0 M in pentane, Aldrich) Tetrahydrofuran (distilled from sodium benzophenone)

Procedure
A solution of 3,4-epoxytetrahydrofuran (80 mg, 930 mmol) in THF (5 mL) cooled to –78 °C is treated dropwise with TMSCH₂Li (2.3 mL, 2.3 mmol, 2.5 eq.). After stirring at –78 °C for 1 h and then at 25 °C for 1 h, phosphate buffer (pH 7, 5 mL) was added. The mixture was extracted with EtOAc (2 x 10 mL), the combined organic layers dried (MgSO₄), filtered and concentrated under reduced pressure. Purification of the residue by column chromatography (SiO₂, 3 : 1 Et₂O : 40 - 60 °C petrol) gave the product as a colourless oil (0.12 g, 73%).

Author's Comments
For optimal yields both the epoxide (distillation, boiling point: 65 °C / 45 mmHg) and THF need to rigorously dried prior to use, all glassware should be flame dried and needles and syringes should be purged with argon. Analogous procedures have been successfully conducted on up to a 5 mmol scale with no reduction in yield.

Data
Rf 0.25 (3 : 1 Et₂O : 40 - 60 °C petrol). ¹H NMR (400 MHz, CDCl₃) 4.83 (s, 1 H, C=CH₂), 4.59 (s, 1 H, C=CH₂), 3.91 - 3.86 (m, 1 H, C(2)-H), 3.57 - 3.50 (m, 1 H, C(1)-H), 3.34 - 3.20 (m, 3 H, C(1)-H and 2 x OH), 1.46 (d, 1 H, J = 14.0 Hz, C(4)-H), 1.21 (d, 1 H, J = 14.0 Hz, C(4)-H), –0.12 (s, 9 H, TMS). ¹³C NMR (100 MHz, CDCl₃) 146.0 (C(3)), 108.2 (C=CH₂), 75.6 (C(2)), 65.5 (C(1)), 23.3 (C(4)), –1.5 (TMS).

Lead Reference
D. M. Hodgson, M. A. H. Stent and F. X. Wilson, Org. Lett., 2001, 3401 – 3403.

Other References

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