Electrophilic sulfur reagent

Reactants with internal nucleophiles are also subject to cyclization by electrophilic sulfur reagents, a reaction known as sulfenylcyclization.92 As for iodolactonization, unsaturated carboxylic acids give products that result from anti addition.93... 

Formation of a bond between two heteroatoms is also of considerable utility in the synthesis of sulfur-containing polyheteroatom systems. Reaction of 1,5-dinucleophiles with electrophilic sulfur reagents such as thionyl chloride or sulfur dichloride leads directly to the heterocycles (e.g. equation 55). A fuller discussion of these types of reaction is given in Chapter 2.28. 

Benzoxepin 185 can be synthesized as shown in Scheme 113 <1966CB634>. The benzothiepin 187 can be obtained by the reaction of an electrophilic sulfur reagent with (Z,Z)-0-bis(-lithiovinyl)benzene 186 which is derived in two steps from tf-phthalaldehyde (Scheme 114) <2003CPB1283, CHEC-III(13.03.9.2)127>. 

In 2005, the application of cinchona alkaloid derivatives as catalysts for enantiose-lective a-sulfenylation of activated C—H bonds in lactones, lactams, and P-dicarbonyl compounds 146 by electrophilic sulfur reagent 147 was reported by Jorgensen and coworkers (Scheme 6.44) [73]. Optically active a-sulfenylated products 148 were obtained in good to excellent yields and up to 86% ee in the presence of 10 mol% (DHQD)2PYR in toluene solvent at —30 or —40°C. Furthermore, the diastereose-lective reduction of a-sulfenylated (3-keto esters to give optically active a-sulfenylated (5-hydroxy esters was also demonstrated. 

The asymmetric a-sulfenylation of ketones is a particularly challenging reaction, as demonstrated by the poor success reported in the stereoselective variants via classical enolate/azaenolate reaction with an electrophilic sulfur reagent [71]. An umpolung approach has been devised by Coltart and co-workers [72] to effect the first asymmetric a-sulfenylation of ketones with arene thiols. Nitroso alkene derivatives, in i/tM-generated under basic conditions from a-chloro oximes, reacted with arene thiols in the presence of cinchona thiourea 27, which promoted the conjugate addition of thiophenol (Scheme 14.25). The chiral nonracemic a-sulfenylated oximes were directly hydrolyzed by IBX to ketones in high yield and good enantioselectivity. 

A variety of reagent combinations add fluorine and sulfur to fluonnated olefins. Typically the olefin is reacted with fluoride ion and a source of electrophilic sulfur, such as sulfur tetrafluonde[757,178,179, 7S0], alkyl or amino sulfur tnfluondes [757, 787],... 

Addition Reactions with Electrophilic Sulfur and Selenium Reagents... 

In many synthetic applications, the sulfur or selenium substituent is subsequently removed by elimination, as will be discussed in Chapter 6. Arenesulfenyl halides, ArSCl, are the most commonly used of the sulfur reagents. A variety of electrophilic selenium reagents have been employed, and several examples are given in Scheme 4.3. 

As has been mentioned above, thermal decarboxylation of heterocycle 36 can be coupled with electrophilic trapping with either bromine or nitro groups to yield the substituted analogues. The same heterocyclic system 59 can be thiolated by treatment either with elemental sulfur (followed by alkylation with an alkyl halide) to afford 60, or the electrophilic thiolating reagent 58 to generate 57 (Scheme 5) <2005HCA1208>. 

Additions ofArSX, ArSeX, and Related Reagents with Electrophilic Sulfur... 

Undoubtedly, the most widely used method for the synthesis of o.p. sulfoxides is the nucleophilic addition of metal organic reagent to an electrophilic sulfur with preestablished chirality, and the subsequent displacement of the sulfoxide. The reason is that either a good kinetic resolution of the sulfinyl chloride, generated first, or high separation factor of the intermediate diastereoisomers formed, permits the sulfinylating agent to be obtained in 100% de. 

Aromatic sultones, unlike the aliphatic analogues, react with nucleophiles at the electrophilic sulfur atom. As an illustration, naphthalene-1,8-sultone (169) reacts with sodium hydroxide, ammonia or a Grignard reagent to give the products (170)-(172) (Scheme 71). The mechanism of these reactions involves initial nucleophilic attack at the sulfur atom with opening of the sultone ring system (Scheme 71). 

Alkanesulfonyl chlorides can also react by an initial elimination in water, mesyl chloride hydrolyses below pH 6.7 by an S 2 reaction of water at sulfur, between pH 6.7 an 11.8 by capture of the sulfene by water and above pH 11.8 by capture of the sulfene with hydroxide ion. An extended study of mesylations of phenols catalysed by various pyridines revealed a competition between the sulfene pathway and a general base-catalysed attack of the phenol, which was dependent on the pAa of both phenol and pyridine, with no mention of an A-mesylpyridinium ion. However, formation of an A-triflylpyr-idinium ion occurs immediately pyridine and triffic anhydride are mixed and this is probably the triflating species. Reaction via an A-sulfonyl quaternary ammonium ion therefore becomes important with more basic amines and more electrophilic sulfonylating reagents. 

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