Anilines Sommelet-Hauser rearrangement

The mechanism of the Gassman indole synthesis bears some resemblance to that of the Fischer indole reaction. An Sn2 displacement of the TV-chlorinated aniline with the a-keto sulfide gives rise to a sulfonium ion. After deprotonation, a [2,3]-sigmatropic rearrangement (Sommelet-Hauser rearrangement) takes place where the weak N-S bond is broken and a strong C-C bond is formed. Similar to the Fischer indole reaction, the resulting imine was transformed into indole after re-aromatization and cyclization. 

In 2003, Alper and co-workers, based on an earlier, reported the synthesis of substituted tosyl-indoles from substituted anilines and isopropylsulfides, introduced a practieal way for the elaboration of multigram scale of the otherwise difficult accessible methyl 7-chloroindole-4-carboxylate, based on the desulfurization and cyclization of a prior Sommelet-Hauser rearranged produet 41, derived from the reaction of methylsulfide 39 with o-chloroaniline derivative 40. 

The mechanism of the indolization of aniline 5 with methylthio-2-propanone 6 is illustrated below. Aniline 5 reacts with f-BuOCl to provide A-chloroaniline 9. This chloroaniline 9 reacts with sulfide 6 to yield azasulfonium salt 10. Deprotonation of the carbon atom adjacent to the sulfur provides the ylide 11. Intramolecular attack of the nucleophilic portion of the ylide 11 in a Sommelet-Hauser type rearrangement produces 12. Proton transfer and re-aromatization leads to 13 after which intramolecular addition of the amine to the carbonyl function generates the carbinolamine 14. Dehydration of 14 by prototropic rearrangement eventually furnishes the indole 8. 

Reaction of benzyne with tertiary aliphatic amines to give anilines via Sommelet-Hauser and/or Stevens-type rearrangements of the intermediate ylid has been documented.362 363... 

The Gassman indole synthesis involves a one-pot process in which a hypohalite, a P-carbonyl sulfide derivative, and a base are added sequentially to an anihne or a substituted aniline to provide 3-thioalkoxyindoles. The mechanism of the Gassman indole synthesis involves a [2,3]-sigmatropic rearrangement (Sommelet-Hauser). The sulfur can be easily removed by hydrogenolysis or Raney nickel. 

Further reaction of A -chloroaniline 6 with ethyl (methyl)thioacetate yields azasulfonium ion 7, which forms ylide 8 upon deprotonation with triethylamine. After the ylide undergoes a [2,3]-Sommelet-Hauser-like rearrangement, a proton transfer and subsequent rearomatization produces the intermediate aniline derivative 9, which upon cyclization forms a transient tetrahedral anion. Collapse of the anion with loss of ethoxide produces the stable oxindole derivative 2. Removal of the methyl thiol functionality with Raney nickel produces the final product 3. 

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