Nucleophilic attack at sulfur

Isothiazoles and isothiazolium cations are attacked by carbanions at sulfur and on recyclization can give thiophenes, illustrated by (147) -> (148). 2-Alkyl-3-isothiazolinones e.g. 149) are also vulnerable to nucleophilic attack at sulfur (72AHC 14)1). 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles generally, soft electrophiles attack at sulfur, cf. (150)— (151). -Butyllithium with 4,5-diphenyl-l,2,3-thiadiazole yields PhC = CPh, probably by initial nucleophilic attack at sulfur. 

Many reactions have been reported where nucleophilic attack at sulfur has been proposed in the mechanism but since the publication of CHEC-II(1996) there have been no further reports of electrophilic attack of 1,2,4-thiadiazoles at the sulfur atom. 

The P2N4S2 ring in 111 is readily susceptible to nucleophilic attack at sulfur. Reactions with organolithium reagents give monolithium derivatives... 

Nucleophilic attack at sulfur is implicated in many reactions of 1,2,4-thiadiazoles <84CHEC-I(6)463> and in general soft nucleophiles attack at sulfur. For example, reaction of 3-hydroxy-5-phenyl-1,2,4-thiadiazole (23) with acetic anhydride in the presence of dbu at 130°C gives the thiazoles (31) and (32) <85JHC1497>. These products may be reasonably explained by the mechanism outlined in Scheme 9 in which the thiadiazole ring is opened by the acetic anhydride carbanion. There is some evidence that (32) may arise from attack of the carbanion on the A-acylated derivative (30a) (Scheme 9) <85JHC1497>. 

Metallation of 3,4-dimethyl-l,2,5-thiadiazole (55) to the anion (56) was accomplished with the use of a nonnucleophilic base, lithium diisopropylamide <82JHC1247>. Nucleophilic attack at sulfur resulted in an alkyllithium reagent <70CJC2006>. The lithiomethyl derivative (56) was carboxylated to (57) with carbon dioxide and converted to the vinyl derivative (58) via an esterification, reduction, mesylation, and base elimination sequence (Scheme 12). 

These electron-rich systems usually show little tendency to react with nucleophiles, but 1,2-dithiins suffer nucleophilic attack at sulfur followed by ring cleavage. 

Electrophilic or Nucleophilic Attack at Sulfur or Oxygen Ring Heteroatoms 495... 

Ferrocene is best deprotonated by r-BuLi/r-BuOK in THF at 0 °C,360 since BuLi alone will not lithiate ferrocene in the absence of TMEDA and leads to multiple lithiation in the presence of TMEDA. In the example below,216 a sulfur electrophile and a Kagan-Sharpless epoxidation lead to the enantiomerically pure sulfinyl ferrocene 398. The sulfinyl group directs stereoselective ortholithiation (see section 2.3.2.2), allowing the formation of products such as 399. Nucleophilic attack at sulfur is avoided by using triisopropylphenyllithium for this lithiation. 

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