Gassman, synthesis

The Gassman synthesis has been a particularly useful method for the synthesis of oxindolcs[lb,8]. Use of methylthioacetate esters in the reactions leads to 3-(methylthio)oxindoles which can be desulfurized with Raney nickel. Desulfurization can also be done by reduction with zinc or tin[10,ll]. 

Oxyindoles are prepared using a modified Gassman synthesis from the chlorosulfonium salt 167 on reaction with substituted anilines <1996TL4631> (Equation 92). 

The Gassman synthesis has been utilized for preparation of a 6,7-dihydroxyoxindole unit of the natural product paraherquamide A via the key intermediate product 62 (Scheme 36) <1996JOC8696, CHEC-III(3.03.6)312>. 

The Gassman synthesis produces sulfur-substituted indoles, but these can easily be hydrogenolysed if required. 

Although isatins having adjacent carbonyls of very different reactivity— amide vs. ketone—undergo a variety of chenucal reactions [86,87], the focus here is on synthetic transformations to indoles. Accordingly, isatins can be reduced directly to indoles (Scheme 11, equations 1-7) [16,89-93]. Given the availability of isatins from aromatic amines (e.g., Sandmeyer synthesis [86], Gassman synthesis [88]), the reduction of isatins to indoles can be an important alternative to other methods. 

The indole nucleus is present in various bioactive molecules and many selective protocols for its construction have been developed. Classical methods for the indole synthesis include the Fischer indole synthesis, the Batcho-Leimgruber synthesis from o-nitrotoluenes and dimethylformamide acetals, the Gassman synthesis from N-haloanilines, the reductive cyclization of o-nitrobenzyl ketones, and the Madelung cyclization of A/ -acyl-o-toluidines [42,43]. 

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