An Efficient Isoprenylation of Xanthones at the C1 Position by Utilizing Anion-Accelerated Aromatic Oxy-Cope Rearrangement
Received: 25 November 2015
Accepted after revision: 14 December 2015
27 January 2016 (online)
Dedicated to the departed Prof. Yoshiro Kobayashi
An effective method for the installation of isoprenyl moiety at the C1 position of xanthone has been developed. Addition of isoprenyl Grignard reagent to 1-fluoroxanthone derivatives proceeded γ-selectively, and the obtained tertiary alcohols underwent aromatic oxy-Cope rearrangement and subsequent elimination of fluoride anion under mild conditions to give 1-isoprenylxanthones in high yields.
Key wordsxanthone - isoprenylation - Grignard reaction - regioselective reaction - oxy-Cope rearrangement
References and Notes
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- 17 Typical Procedure for the Reaction of 2a: To a solution of 2a (285 mg, 1.00 mmol) in THF (10 mL) in a two-necked brown-glass flask was added KHMDS (0.5 M solution in toluene, 4.4 mL, 2.2 mmol) followed by a solution of 18-crown-6 (795 mg, 3.01 mmol) in THF (10 mL) at –78 °C. After carefully purging air with argon (3 ×), the reaction mixture was quickly warmed to 0 °C by replacing the dry ice/acetone bath with the ice-cold water bath, and the stirring was continued for 5 min. The reaction was quenched with sat. aq NH4Cl solution, and the products were extracted with EtOAc (3 ×). The combined organic extracts were washed with brine and dried over Na2SO4. Removal of the solvents in vacuo and purification by column chromatography (silica gel, hexane–EtOAc, 20:1) gave 3a (225 mg, 85%) as a colorless oil and 4a (25 mg, 9%) as a colorless oil.
- 18 The reaction of alcohol 16 gave 17 (88%) and 18 (7%; Scheme 5).
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- 23 The reaction of alcohol 19 gave 20 as the major product (Scheme 6).
- 24 The reaction of alcohol 22 gave 23 and 24 in a ratio of 89:11 (Scheme 7).
For recent reviews on the synthesis of prenylated xanthones, see:
For examples of the synthesis of prenylated xanthones by utilizing the Claisen rearrangement, see:
Note that in the precursor benzophenones for 1-prenylxanthones, at least three of the four ortho positions of the carbonyl group are occupied by substituents, including a prenyl moiety and two functional groups for the ether bond formation. For the related discussions, see:
For examples of anion-accelerated aromatic oxy-Cope rearrangement, see:
For recent reviews on anion-accelerated oxy-Cope rearrangement, see:
For examples of [3,3]-sigmatropic rearrangement of organofluorine compounds, see:
For the photoenolization of diarylketone derivatives, see:
For recent examples of photo-induced reactions of xanthone derivatives, see: