The scheme below summarizes the results from a study into the optimum conditions needed for a key step in the synthesis of the proposed structure of carambolaflavone, a natural product that has antidiabetic properties. Note that $\ce{Sc^3+}$ acts as a Lewis acid in these reactions.

Synthesis of the proposed structure of carambolaflavone, a natural product that has antidiabetic properties.

I'm very confused about how the acid is coordinating to the Benzene derivative here?

  • 3
    $\begingroup$ The Sc3+ may bind to the benzene derivative but that is not important. The binding to the oxygen of the tetrahydropyran is what matters. $\endgroup$
    – Waylander
    May 3, 2019 at 8:13
  • $\begingroup$ Hi thanks for your answer, but I'm afraid I'm not quite understanding what you mean? $\endgroup$
    – J. Deans
    May 3, 2019 at 9:26
  • 1
    $\begingroup$ The key intermediate in the reaction step is an oxonium species R-O=R+ created by the Scandium ion binding to the acetal oxygens on the tetrahydropyan ring. In the first step it binds to the carbonyl of OAc gruop, in the second step to the oxygen of the THP-OPh $\endgroup$
    – Waylander
    May 3, 2019 at 9:42

1 Answer 1


@Waylander provided a correct written explanation for your question. I'll expand on his comments by considering the effect of temperature and provide diagrams.

Using M+ = Sc+3 to save some space, the Lewis acid coordinates with the more basic of the two acetate oxygens in 1 to provide the reactive oxonium species 2. [The oxonium species is planar about the double bond but I have left it in the chair conformation as a space-saving device.] This step may be reversible. At room temperature there is not sufficient activation energy to permit substitution of the aromatic ring. Following the red arrows of phenolic species 3, axial attack of the phenol oxygen occurs on the oxonium ion 2 to form, kinetically, compound 4. At 50 oC this reaction is reversible catalyzed by Sc+3 to reform 2 and 3 via the blue arrows. Following the green arrows, now there is sufficient energy to disrupt the aromaticity of 3 and allow for axial attack by carbon on the oxonium ion 2 to form, kinetically, structure 5. An increase of temperature to 70 oC permits coordination of the tetrahydropyran oxygen with the Lewis acid permitting ring opening, bond rotation about the red bond in 6 and ring closure of conformation 7 forming the thermodynamically stable, all equatorial tetrahydropyran ring of 8. [Structures 6 and 7 may also be drawn as benzyl cations with the carbonyl oxygen protonated.]

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