Azasulfonium salts

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. 

The orf/to-formylation of 2-aminopyridines can be effected via the rearrangement of the azasulfonium salt prepared from a 2-aminopyridine, 1,3-dithiane, f-butyl hypochlorite and sodium methoxide (74CC685). The crude sulfilimine (815) was refluxed in f-butanol containing potassium f-butoxide to yield the dithioacetal (816). Hydrolysis of (816) with mercury(II) oxide/boron trifluoride etherate gave the aldehyde (817 Scheme 191). This method should be applicable to the formylation of other heterocyclic amines. 

Very few examples of electrophilic attack at sulfur(II) have been reported for these systems, with the exception of oxidation. Alkylation of the benzothiadiazine (88) with trimethyloxonium tetrafluoroborate gave a poor yield of the imino ether (89). The major product (90) resulted from alkylation at sulfur followed by hydrolytic ring opening of the resulting azasulfonium salt (79JCR(S)214). 

An alternative approach is also feasible. The phenol is treated with the complex of NCS and dimethyl sulfide (4, 87-90) to give the azasulfonium salt (d), which is converted as shown to the o-methylthiomethyl phenol (4). ... 

A total synthesis of (+)-paspalicine and (+)-paspalinine took advantage of the Gassman indole synthesis. The thiomethyl ketone was treated with A-chloroaniline (prepared by mixing aniline with t-butyl hypochlorite) to afford the azasulfonium salt, which was transformed into anilinylsulfide upon treatment with triethylamine. Desulfurization with Raney nickel was followed by the acid-catalyzed cyclization to give the hexacyclic indole intermediate. 

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