Pyrroles sulfenylation

In the reaction of CF Cl3 SCl with triethylamine, the yield of the product (CF Cl3 S)2C=CHN(C2H5)2 decreases with decreasing n [fri] (equation 7) (Table 2). 2,3,4,5-Tetrakis(trifluoromethylthio)pyrrole salts react with sulfenyl chloride or SjjCl2 (x = 1,2) to give N-sulfenylaled pyrroles as well as dipyrrolylsulfane and -disulfene. Pentakis(trifluoroniethylthio)pyrrole is a mild sulfenylating... 

Compounds with excess of tt electrons, as for example, pyrrole and thiophene, form a large number of substitution products in their reactions with perfluorohalogenosulfenyl halides 47, 60). Thus pyrrole reacts with an equimolar quantity of a sulfenyl chloride of the series CFwCl3 n-SCl (w = 1, 2, 3) with the formation of a mixture of isomers of mono-substituted compounds ... 

Indole and carbazole, which can be regarded theoretically as derivatives of pyrrole through its anellation with one or two benzene rings, show variable behavior toward sulfenyl halides ... 

Pyridine iV-sulfides are known only in the form of their derivatives. Thus, 1-arylthiopyridinium cations (from pyridine and sulfenyl chloride) react with KCN to form ArSCN and pyridine (81CC703). Pyridine-sulfur trioxide is a mild sulfonating reagent, used for sulfonation of furan and pyrrole. 

Alkylthio and arylthio derivatives of pyrroles and indoles are readily obtained from their reactions with the appropriate alkyl or aryl sulfenyl chlorides (e.g. B-77MI30502, B-77MI30506, 77CB67, 79HC(25-3)1>. 

A facile and efficient sulfenylation method using quinone mono-0,5 -acetals (793 or PhS-analog) under mild conditions was successfully applied to various pyrroles and indoles (Equations 193 and 194) <2001JOC2434>. The phenylsulfenyl analog of compound 793 reacted similarly to give regioselectively the corresponding sulfide in 43-99% yields. 

Sulfenylation of pyrrole and thiocyanation of pyrrole or of 1-phenylsulfonylpyrrole also provide means for the electrophihc introduction of sulfur groups, at lower oxidation levels, and in contrast to the sulfonations, at the pyrrole a-position. 

Pyrrole and 1-methylpyrrole can be sulfinylated by sulfinyl chlorides or A-(phenyl-sulfinyl)succinimide. The products are prone to rearrange to the 3-isomers on contact with acid <80JOC5336>. A phenylsulfinyl group has been introduced at C3 of the indole ring by 3-sulfenylation of AT-lithioindole with diphenyl disulfide, followed by A-sulfonylation and oxidation to the sulfoxide <89JOCi782>. Sulfenylindoles can be oxidized to sulfones by MCPBA <93JMC1425>. 

The insertion reaction between an isocyanide and a sulfenyl chloride generates an intermediate (e.g. equation 4.42), which can undergo 1,3-cycloaddition reactions with electron-deficient species to form pyrroles and pyrrolines. Potassium fluoride supported on alumina is a mild basic catalyst for this process [161]. 

Haas and coworkers performed a series of studies on the reactivity of the perituoroalkyl sulfenyl chlorides with electron rich heterocyclic compounds, to give CFjS derivatives. Pyrroles are good substrates for reaction with trifluoromethyl sulfenyl chloride due to higher nucleophilicity compared to benzene [45]. An excess of reagent gives bis-CCFjS) pyrrole derivatives as shown in Scheme 16. 

Such a reversible blocking of the 2-position by sulfenylation was of particular interest in the synthesis of bromo-derivatives of indolyl-3-propionic acid. Specific bromination or nitration of the benzene ring of an indole is normally difficult to achieve, since the pyrrole ring also will react with electrophilic reagents. As an example, 5-bromoindole-3-propionic acid has been prepared using this reversible protection, that is by bromination of the 2-sulfenylated compound and removal of the arylthio group by the two consecutive reactions with NBS and NaBKi (727). 

---