Gassman Indole Synthesis - Reaction Mechanism

Reaction Mechanism

The reaction mechanism of the Gassman indole synthesis is divided among three steps.

The first step is the oxidation of the aniline 1 using tert-butyl hypochlorite (tBuOCl) to give the chloramine 2.

The second step is the addition of the ketone to give the sulfonium ion 3, and is typically done at low temperatures (-78 °C).

The third and final step is the addition of a base, which in this case is triethylamine. Upon warming to room temperature, the base will deprotonate the sulfonium ion creating the sulfonium ylide 4, which quickly undergoes a -sigmatropic rearrangement to give the ketone 5. The ketone 5 will undergo a facile condensation to give the desired 3-thiomethylindole 6.

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