A Convenient Triisobutylaluminium (TIBAL)-Promoted Johnson-Claisen Approach to γ,δ-Unsaturated Alcohols

Abstract

Mixed ortho esters derived from allylic alcohols undergo methanol elimination in the presence of triisobutylaluminium (TIBAL) at room temperature to form mixed ketene acetals. TIBAL then promotes immediate Claisen rearrangement of these intermediates, and subsequent reduction of the ester products, to give unsaturated γ,δ-primary alcohols in a convenient, one-pot procedure.

triisobutylaluminium - mixed ortho esters - ketene di­methyl acetal - Johnson-Claisen rearrangement - γ,δ-unsaturated alcohols

References and Notes

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12

Mixed ortho esters derived from tertiary alcohols cannot be synthesised by the standard method which we employ. [8] Ketene dimethyl acetal (3.17 mL, 33 mmol) and propionic acid (˜0.1 mL) were added to linalool (4 mL, 22 mmol; entry 11) and stirred at r.t. for 1.5 h. Distillation of the crude reaction mixture allowed isolation of the mixed ortho ester 28 as a clear liquid (1.5 g, 28%).

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14

In a typical experiment, ketene dimethyl acetal (3 mmol per hydroxyl group) was added cautiously to the anhyd allylic alcohol (1 mmol) and stirred rapidly at r.t. under argon for
˜2 h. Excess ketene dimethyl acetal was removed in vacuo, giving the pure mixed ortho ester in quantitative yield. [8] To the same vessel, TIBAL (6 equiv, 1 M solution in toluene) was added at r.t. under argon over ˜2 min. The reaction immediately became exothermic and was typically allowed to stir at r.t. overnight, however, the reaction was usually complete after ˜6 h. DIBAL (1-2 equiv, 1 M in toluene) was added and the reaction was stirred for 2 h to reduce any remaining traces of ester. The reaction was quenched at
-78 ˚C by the cautious addition of 5% HCl and then allowing the reaction to warm to room temperature. The aqueous layer was extracted with Et₂O (3 × 40 mL) and the combined organic fractions were dried (Na₂SO₄), filtered and evaporated to give the crude product as a yellow oil (we found that the HCl quench worked better than aqueous NaOH [¹0] [¹¹] or aqueous sodium citrate solution [9] as it avoided formation of solid aluminum salts). Silica column chroma-tography was required to separate residual starting alcohol from the rearranged γ,δ-unsaturated primary alcohol. All new compounds were characterised by ^¹H and ^¹³C NMR and/or by HRMS and elemental analysis. The spectroscopic data can be found in the supplementary information.