Sulfur electrophilic

Thioglycosides can be activated for gfycosylation reactions with sulfur electrophiles, e.g., with dimethyl(methylthio)sulfonium triflate or with methanesulfenyi bromide and silver(l +) to form reactive sulfonium intermediates (F. Dasgupta, 1988). 

Reaction with Sulfur Electrophiles. Bisa2iridine compounds can be prepared from sulfur dichloride, thionyl chloride, or sulfuryl chloride... 

The first direct dehydrative glycosylation promoted by sulfur electrophiles was reported by Leroux and Perlin [105]. In this reaction (Scheme 3.9), activation of... 

The acetylacetonate ring is attacked by a variety of sulfur electrophiles (25, 26). For example, reaction of these chelates with thiocyanogen proceeds smoothly at —10° to give high yields of the tristhiocyanochelates (XIII). The chemical reactivity of the thiocyano groups on these rings has not yet been studied. 

Reaction with Sulfur Electrophiles. Bisazitidine compounds can be prepared from sulfur dichloride, thionyl chloride, or sulfuryl chloride and ethyleneimine (288). The products are, respectively, l,T-thiobisaziridine [2881-79-0] (X = S), l,T-dithiobisaziridine [1623-84-3] (X = S—S),... 

The lactonization of 5,7-dienoic acids with selenium and sulfur electrophiles generates 8-lactones by regioselective 1,4-addition to the diene (equation 36).s2a With substitution at the 8-position, reaction with PhSeCl or PhSCl gave a 1 1 mixture of rapidly interconverting 1,2- and 1,4-addition products. This inter-conversion, presumably via a 1,3-rearrangement,S2b was not observed with the alkylthio adduct. An example of conjugate cyclization of an enyne system to form an allenyl product has also been reported (equation 37).112... 

Cz Symmetrical and enantiomerically pure thiepines were prepared <1999TL813, 20060BC2218>. Diaryl compounds with two chiral centers 176 were lithiated with sec-butyl lithium in THF at — 78 °C to give the bis-ortho-lithiated 177. Reaction of sulfur diimidazole led to thiepines 26 and 178 in 37—48% yield (Scheme 20). The use of elemental sulfur, thionyl chloride, sulfuryl chloride, SC12, S02(imidazolyl)2, SO(imidazolyl)2, sulfur ditriazole, and sulfur bisbenzotriazole, as a sulfur electrophile, gave cyclized products in poor results. 

The thiepines 180 were prepared via a bromine/lithium exchange for /7/%-lithiation of 179 (Equation 26). Lithiation was achieved using /-BuLi (2equiv for each bromine) and sulfur diimidazole was used as the sulfur electrophile. Thiepines 180a-d were obtained in 12-38% yield. 

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. 

With a sulfur electrophile, mixed thioselenoacetals 177 form which may then undergo a second selenium-lithium exchange, leading to fully substituted a-thio organolithiums 178.143... 

With dimethyl disulfide as the electrophile the cis/trans-ratio is 90 10 even in tetrahydrofuran. Competition experiments show that this reaction is much faster than the usual alkylations, which afford mainly frans-compounds68). With the sulfur electrophile a single electron transfer (SET) seems likely generating a cyclopropyl radical as a reactive species, which naturally displays a different selectivity compared to the enolate anion. 

This mechanistic picture is supported by the fact that the ketene acetal moiety in 170 can be trapped by suitable electrophiles providing adducts 171. Ring cleaving selenenylation and sulfenylation is therefore possible at —78 °C in the presence of a few drops of TiCl (Table 5, entries 1—5)91). Without Lewis acid no reaction with the sulfur electrophile could be observed at room temperature and incorporation of the phenylselenenyl group occurs only rather slowly. 

Reactions of enol ethers with halogen and sulfur electrophiles... 

This reaction provides a useful way of introducing a double bond next to a carbonyl group. Here it is in a synthesis by Barry Trost of the Queen Bee Substance (the compound fed by the workers to those bee larvae destined to become queens). The compound is also a pheromone of the termite and is used to trap these destructive pests. Trost started with the monoester of a dicarboxylic acid, which he converted to a methyl ketone by reacting the acyl chloride with a cuprate. The ketone was then protected as a dioxolane derivative to prevent it enolizing, and the sulfur was introduced by reacting the enolate of the ester with the sulfur electrophile MeSSMe. 

Phenyl-5-chlorotriazole 1-oxides 330 are deprotonated with NaH in DMF. The resulting species 331 react with carbon, silicon, and sulfur electrophiles to give substituted products 332 in good yields. Similarly, deprotonation of 1-substituted pyrazole 2-oxides followed by addition of dimethyl disulfide affords 3- and 5-methylthio as well as 3,5-bis (methylthio)pyrazoles. 

Phenylenediamine is readily converted by HN02 into 1,2,3-benzotriazole 438 and by SOCl2 into 2,1,3-benzothia-diazole 439. Best synthetic methods for the preparation of 1,2,3-benzotriazoles are summarized in the related section of CHEC-III most important procedures are based on the reactions of substituted 0-pheny-lenediamines with nitrous acid or nitrites as illustrated by Scheme 227 <2006JME4762>. Likewise, the annulated thiadiazoles are commonly synthesized by the reaction of sulfur electrophiles with appropriate 1,2-diamines (e.g., Scheme 228) <1999JA10281, 2004BML5045, CHEC-III(5.09.9.2)550>. 

The sulfenylation of metalloimines is equally applicable to ketones, although using more reactive sulfur electrophiles it is possible to bring about reaction on the unmetallated enamine. ° Sulfenylation of ketone enol silyl ethers also proceeds well with the more reactive sulfur species. Sulfenamides and their derivatives e.g. 11) are particularly suited to the direct sulfenylation of ketones and active methylene compounds such as -diketones, -keto esters and malonates, which undergo facile reaction at room temperature (equation 5). This procedure, however, does not appear to have been exploited for the dehydrogenation of active methylene compounds icf. Section 2.2.4.1). By preparing the dianion (13)... 

Electrophilic reaction at sulfur Electrophilic reaction at nitrogen Ring opening Other reactions... 

Another concept for the activation of thioglycosides is their reaction with soft sulfur electrophiles. The first reagents of this type were dimethyl(methylthio)sulfonium triflate (DMTST, 83) and the corresponding tetrafluoroborate (DMTSF, 84) (Figure 4.4) [86,183-185], which are powerful methylsulfenylating agents (E = SMe) (Scheme 4.15), and are still extensively used. 

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