Lithiation in flavones, chromones, coumarins, and benzofuran derivatives

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Abstract
Flavones are lithiated at position 3 by lithium di-isopropylamide in tetrahydrofuran at –78 °C and the products are stable at that temperature. Appropriate reagents replace the lithium by carboxy, ethoxycarbonyl, mercapto, methylthio, trimethylsilyl, hydroxy, and other groups, sometimes giving products not previously available. Benzofurans are preferentially lithiated at position 2 if this is free, and may not be attacked if it is blocked, but if there is an activating group (i.e., one able to co-ordinate with the lithium cation) at position 2, then lithiation occurs at position 3. In the benzofuran series ring-opening is easier and lithiation often leads directly to acetylenic phenols. Chromones can be lithiated at positions 2 and 3 depending upon the substitution pattern and whether the substituents are activating. Aurones are not easily deprotonated, and only the acetylenic phenol arising from ring opening was found in the one successful case. Coumarins tend to behave simply as esters and give amides with the lithiating reagent, but 4-methoxycoumarin is readily lithiated at position 3. It is suggested that 3-deprotonation in ethers occurs easily only when there is an ether link antiperiplanar to the proton removed, and that the lithiated species are really unstable intermediates in trans-eliminations leading to alkyne derivatives.

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