Sulfenium ions

Harring, S. R. Livinghouse, T. Sulfenium ion promoted polyene cyclizations in natural product synthesis. An efficient biomimetic-like synthesis of ( )-nimbidiol. Tetrahedron Lett. 1989, 30, 1499-1502. 

A combination of 2,3 sigmatropic rearrangement (Pummerer-type reaction) followed by an electrophilic aromatic substitution of the intermediate sulfenium ion, the formation of an iminium ion and, finally, a second electrophilic aromatic substitution, was used by Daich and coworkers for the synthesis of iso-indolo-isoquinolinones as 4-314 (Scheme 4.68) [106]. Thus, reaction of the two diastereo-meric sulfoxides 4-313, easily obtainable from 4-312 by a Grignard reaction and oxidation, led to 4-314 as a single product after crystallization in 42% yield. 

In earlier days it was fairly common to suggest that sulfenium ions, RS+, were involved as intermediates in a number of these substitutions, particularly those in which sulfenyl halides RSX reacted with very weak nucleophiles, or those where electrophilic catalysis of the substitution was observed (Parker and Kharasch, 1959). However, it has since become evident (Owsley and Helmkamp, 1967 Helmkamp et al., 1968 Capozzi et al., 1975) that sulfenium ions are almost impossible to generate as intermediates. For example, Capozzi et al., (1975) showed that although treatment of a sulfenyl chloride RSC1 with the powerful Lewis acid antimony pentafluoride led to the complete conversion of the sulfenyl chloride to a cation, what was formed was, not the sulfenium ion RS+, but rather the cation [59] in reaction (172). These results, and others... 

RE Benesch, R Benesch. The mechanism of disulfide interchange in acid solution role of sulfenium ions. J Am Chem Soc 80, 1666, 1958. 

Thus, SCI and SCN have different electron-attraction properties. That conclusion was not predictable a priori. Until recently, the extent of polarization in the SCI group has been considered to be comparable to that in the SCN group, according to the S8+-X8 scheme. For instance, Kharash et al. (1953), have pointed out that nitroaryl thiocyanates as well as nitroaryl sulfenyl chlorides, when dissolved in concentrated sulfuric acid, are converted into the same nitroaryl sulfenium ions, 02NArS+. However, the preceding findings indicate otherwise. 

Polyene cyctization.1 The reaction of C6H5SOCH3 and BF3 with the diene 1 in CH3N02 initiates cyclization to the tricyclic ring system 2 via a sulfenium ion. This product was converted to the diterpene nimbidiol (3) by reductive desulfuration (lithium naphthalenide) and oxidative decyanation (SnCl2), and demethylation (BBrj). 

The reaction takes a different course with 5-phenylamino-l,2,3,4-thiatriazole, affording 2-aminobenzothiazole by electrophilic attack of the sulfenium ion on the aryl group (equation 27) <64AHC(3)263). 

We view acetylenic sulfoxide 1 as a two-carbon synthon in alkaloid synthesis. Our general approach, as depicted in Scheme 4, called for a Michael addition of Nu1 to the terminal acetylenic position followed by a cyclization by Nu2 (an intramolecular second Michael addition). This Michael addition cyclization step will build up the basic skeleton of the alkaloid system and at the same time control the absolute stereochemistry of the newly created chiral center through asymmetric induction of the chiral sulfoxide moiety. Finally, the sulfoxide can be transformed to another functional group (X) or used to promote the formation of another bond with Nu3 via trapping of the sulfenium ion intermediate under Pummerer rearrangement conditions (Scheme 4). 

In summary, vinyl sulfoxide (or its equivalent 56) was adopted as a two-carbon synthon for the syntheses of alkaloids (39,43ab,45ab), furans (51), pyrroles (52), and l,3-dithiole-2-one (60). Our overall strategy is summarized in Scheme 14. Michael addition of Nu1 to the vinyl sulfoxide followed by intramolecular trapping of the presumed sulfenium ion Pummerer rearrangement intermedia-... 

Incorrect Disulfide Formation. This reaction occurs in neutral and alkaline pH conditions. Under such conditions, deamidation also occurs. The thiols (formed by beta elimination) can promote the disufide bond formation [8]. In an acidic environment, sulfenium ion promotes the incorrect disulfide bonds [9]. Proteins with scrambled disulfide bridges have been shown to yield native structure by incubating the protein with small amounts of mercaptoethanol or Cys. 

Edstrom ED, Livinghouse T. New methods for the generation of episulfonium ions. An application to the synthesis of carbocycles via sulfenium ion promoted arene-alkene cycli-zations./. Am. Chem. Soc. 1986 108 1334-1336. 

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