One of my labs had the following reaction:


I understand the Pictet Spengler mechanism. However, I am confused about the decarboxylation. I cannot come up with a way in which this decarboxylation would be acid catalyzed. Here is what I have for the Pictet mechanism:


I have been trying to figure out the acid catalyzed decarboxylation for several days now but I cannot. This is the closest I can come up with, but I'm not sure that this is correct:

Proposed Mechanism


  • 3
    $\begingroup$ If you protonate the beta position of the indole, the resultant immonium salt is isoelectronic with a a beta-keto acid, which readily decarboxylate. $\endgroup$
    – user55119
    Apr 22, 2021 at 0:39

1 Answer 1


Your suggested mechanism should be acceptable (need two more steps, protonation and deprotonation, see last two steps of my scheme below), if you have isolated the carboxylic acid product (compound $\bf{1}$ in my scheme). If compound $\bf{1}$ is not isolable, I suggest following path would be taken to decarboxylation:

Protonation and decarboxylation

Your reaction is an analog to Pictet Spengler reaction (Wikipedia). When the intermediate $\bf{I}$ is formed during the reaction as depicted in the mechanism, 1,2-hydride transfer is possible to give more stable carbocation $\bf{II}$, which is resonance stabilized $(\bf{\ce{II <-> III}})$. The intermediate $\bf{III}$ can easily undergo decarboxylation to give some what stable enamine product, $\bf{2}$. In acidic medium, this enamine $\bf{2}$ would undergo protonation to give the intermediate $\bf{IV}$, which would then deprotonated to gain aromaticity and give thermodynamically stable indole product, $\bf{3}$ (the intended product).


Your Answer

By clicking “Post Your Answer”, you agree to our terms of service and acknowledge you have read our privacy policy.

Not the answer you're looking for? Browse other questions tagged or ask your own question.