Transformations with Sulfur-Containing Nucleophiles

The reaction of oxiranes with thiols permits the preparation of a-hydroxyalkyl thioethers. Reactions with thiophenols are presented in Eqs. 306 and 307.1  

An account has also been given of the reaction between benzylmercaptan and cis-benzene trioxide.With a-mercapto esters, p-substituted phenyloxiranes undergo normal opening, without being affected by the substituents on the benzene ring. Chalcone oxides react with mercaptan with accompanying C-C bond cleavage (Eq. 308).  

The great variety of transformations that can occur with other sulfur-containing nucleophiles are illustrated by the following experimental observations. Oxiranes react with sulfurated borohydrides in a similar way as the hydrogen sulfide in a basic medium symmetric bis hydroxyethyl disulfides are formed. c/s-benzene trioxide gives di- and triadducts with A, A-diphenylthiocarbamide. Reports have appeared on the reactions between oxirane and -decylmercaptan, butadiene-monooxirane derivatives and mercaptans, and methyloxirane and sulfite ion.  

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Methods based on the pyridine to thieno[3,2-c]pyridine transformation are less well developed. Most of the above-described procedures are based on the nucleophilic displacement of the substituent at position 4 of the pyridine ring with a sulfur-containing fragment followed by cyclization of the resulting product. For example, the reaction of 4-chloropyridines 286 with methyl thioglycolate produced 287 and 288 in one step as a result of the replacement of the chlorine atom and Thorpe or Thorpe Dieckmann cyclization (1987JHC85). 

Scheme 20.2S describes the work published by Kawasaki s group where they used a combination of dimethylsulfoxide and trifluoroacetic anhydride as source of trifluoroacetylated sulfonium ion 109 which reacted with 108 generating the new sulfonium salt 110 that underwent the loss of the sulfur-containing moiety promoted by nucleophilic attack. The nucleophile could be an alcohol, thiol, amine or organometallic species, or even another heterocyclic substrate. In cases where the nucleophile was a sulfoxide, the reaction led to an overall CH2 oxidation (Scheme 20.2S). Kawasaki s results suggest that this transformation, based on an interrupted Pummerer rearrangement, could be applied in the synthesis of biologically active tetrahydrocarbazoles and analogues fFigure 20.2T...

Since dioxiranes are electrophilic oxidants, heteroatom functionalities with lone pair electrons are among the most reactive substrates towards oxidation. Among such nucleophilic heteroatom-type substrates, those that contain a nitrogen, sulfur or phosphorus atom, or a C=X functionality (where X is N or S), have been most extensively employed, mainly in view of the usefulness of the resulting oxidation products. Some less studied heteroatoms include oxygen, selenium, halogen and the metal centers in organometallic compounds. These transformations are summarized in Scheme 10. We shall present the substrate classes separately, since the heteroatom oxidation is quite substrate-dependent. 

Sulfur donors may also be introduced by the primary transformation of the triol into a functionalized thiethane (Equation (10)). Subsequent addition of two potentially different phosphorus nucleophiles leads to tripod ligands containing two phosphane donors together with an SH function ((84), (85), (87), (88)). 

A PLP cofactor attached to the lysine in an His-Lys-X-X-X-Pro-X-Gly-X-Gly motif is a crucial feature of these proteins. Additionally crucial is a conserved cysteinyl residue, which serves as the persulfide site. These proteins belong to fold-type 1 of PLP-dependent enzymes and are homodimers. Each monomer is subdivided into a large domain with one molecule of PLP in aldimine linkage with a Lys residue and a small domain, where the critical cysteinyl residue is located in the middle of a loop. An extended lohe in CDS contains the conserved Cys and constitutes one side of the entrance to the active site. This lohe in CSD may he responsible for the ability of the enzyme to discriminate between selenocysteine and cysteine. NifS binds and transforms the cysteine substrate in a manner usual for PLP-containing enzymes up to the stage of the central quinonoid intermediate. Cysteine desulfuration is initiated by the formation of a Schifif base between cysteine and PLP, followed by the abstraction of sulfur from the substrate and formation of an enzyme-bound cysteine persulfide and alanine via a ketimine intermediate. The cysteine residue acts as a nucleophile and attacks the sulfhydryl... 

AU ethioIates and Selenolates. Sodium alkynethiolates are generated from 1,2,3-thiadiazoles (16) and reacted with CS2. Nucleophilic attack of sodium alkynethiolates to CS2 followed by the intramolecular cyclization proceeded to give 1,3-dithiole-2-thiones (17) in 57-98% yields (eq 2)P Lithium alkynethiolates, which are derived from terminal acetylenes, BuLi, TMEDA, and elemental sulfur, can also be used in this cyclization reaction (eq 13). In the case of the lithium salts, CS2 is added at —90 °C, and the reaction mixture is quenched by adding water containing THF at this temperature to lead to (17). Lithium alkyneselenolates participate in this type of transformation (eq 14). The reaction mixture is quenched with alkyl thiocyanates or a combination of elemental selenium and alkyl iodides to give 1,3-selenothiole-2-thiones (18) in 80-98% yields. The reaction is quenched in a similar manner to that from the lithium alkynethiolates. ... 

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