Gassman indole synthesis

What is Gassman indole synthesis?

In 1973, Gassman et al. first reported a reaction that has since become a versatile method for preparing various types of substituted indoles. This method involves treating anilines sequentially with tert-butyl chlorite, β-keto sulfide, triethylamine, and Raney nickel, if desulfurization is necessary. Although this is a multistep reaction, it can essentially be performed in a single pot and has been shown to produce good yields of both 1- and 2-substituted, as well as 2,7-disubstituted indoles.

Gassman indole synthesis - general reaction scheme
Gassman indole synthesis

Compared to the commonly used Fischer indole synthesis method, this approach offers several advantages. For example, it uses a cheaper and more easily accessible starting material and can be applied to prepare 1-, 2-, 4-, 5-, 6-, or 7-substituted indoles. Additionally, it involves milder reaction conditions that do not require strong acids or bases and typically result in higher yields than those achieved with the Fischer indole synthesis. By contrast, the Fischer indole synthesis relies on appropriately substituted phenylhydrazine or 1,1-disubstituted hydrazine to produce the desired indole derivatives.