Thioether Derivatives

Protection of thiol groups is a substantive issue in peptide chemistry where protection and deprotection of cysteine and the attendant problem of disulfide bond formation is a major challenge. An authoritative review of the subject by Moroder and co-workers can be found in Synthesis of Peptides and Peptidonth metics (Houben-Weyl) Vol E22a.  

Most thiol protecting groups in common use are 5-alkyl derivatives because thiol esters and carbonates are much more easily hydrolysed than their oxygen counterparts. 

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In contrast to the large number of chiral pyridine derivatives used as ligands of metal complexes in asymmetric catalysis, only a few examples of chiral sulfur-containing pyridine ligands have so far been reported, such as pyridine thioethers derived from ( + )-camphor depicted in Scheme 1.33, which were assessed in the test reaction providing enantioselectivities of up to 76% ee. The related 2,2 -bipyridine thioethers were also prepared but showed a lower stereodilferentiating capability in the test reaction. 

Several Pd11 complexes with thiolate or thioether derivative ligands have been studied to be applied in the hydroxycarbonylation reaction.394 Aminothiolate complexes of palladium with PPh3 catalyze the conversion of styrene to 2-phenylpropionic acid in high yield and excellent regioselectivity.644 Under mild conditions and in the presence of a catalytic amount of an S, TV-chelated palladium or//zo-amino-arenethiolate complex, styrene reacts with CO and oxalic acid or water to selectively give 2-phenylpropanic aid in high yield.645... 

Gerin M, Tardif R, Brodeur J. 1988. Determination of specific urinary thioethers derived from acrylonitrile and ethylene oxide. IARC Sci Pub 275-278. 

Cysteine sulfhydryls and cystine disulfides may undergo a variety of reactions, including alkylation to form stable thioether derivatives, acylation to form relatively unstable thioesters, and a number of oxidation and reduction processes (Figure 1.10). Derivatization of the side chain sulfhydryl of cysteine is one of the most important reactions of modification and conjugation techniques for proteins. 

Figure 1.120 The reaction of NEM with sulfhydryl groups yields a thioether derivative, permanently blocking the thiol.

The formation of rings that contain a thioether linkage does not appear to be catalyzed efficiently by Ru, even when terminal olefins are present. On the other hand, molybdenum appears to work relatively well, as shown in Eqs. 30 [207] and 31 [208]. Under some conditions polymerization (ADMET) to give poly-thioethers is a possible alternative [26]. Aryloxide tungsten catalysts have also been employed successfully to prepare thioether derivatives [107,166,169]. Apparently the mismatch between a hard earlier metal center and a soft sulfur donor is what allows thioethers to be tolerated by molybdenum and tungsten. Similar arguments could be used to explain why cyclometalated aryloxycarbene complexes of tungsten have been successfully employed to prepare a variety of cyclic olefins such as the phosphine shown in Eq. 32 [107,193]. 

The reaction of the thiolated PVC with Chloramine T carried out and the structure ( ) of the resultant polymer was examined (1 ). In the case of phenyl-thioether, the sulfilimine structure (2) was mainly produced accompanied with, in part, the sulfenamide structure (8,) binded to the main chain with N atom, the case of allyl thioether derivative containing C=C moiety in the pendent group, the sulfilimine (9) formed rearranged exclusively in Claisen type to the sulfenamide structure (10) connected to the main chain with S atom. 

Activated aryl halides react with thiols [e.g. 4] to produce aryl thioethers and thioethers, derived from non-activated aryl halides, can be synthesized via the Cr(CO), complexes of the haloarenes [29] (Scheme 4.2, see also Chapter 2). 

The localization of a double bond is an important step in structure elucidation and therefore, it is not astonishing that numerous approaches have been made to overcome the above limitations. The methods to freeze isomerization include i) epoxidation [64], ii) iron and copper ion chemical ionization [65,66], iii) field ionization [67], iv) collision-induced dissociation [60], v) formation of thioether derivatives, [68,69] and others. 

Similar SCS-Pd(II) complexes have also been used to prepare isolated nanometer-sized objects within a decanethiol self assembled monolayer on gold [88]. In this chemistry, the thioether derivative of a pyridine complex of the SCS-Pd(ll) complex 22 was first prepared and immobilized on gold as part of a self assembled monolayer. Then the much better phosphine ligand... 

The X-ray crystal structure determinations of thieno[2,3-c]pyridine imines, 38, have been carried out. When the imine contains weak donor and acceptor groups, as in the thioether derivative, the compound is twisted however, the analogous bromo compound is planar <1998J(P2)437>. 

Oxidation of thioethers derived from the natural chirality pool , the readily available lactic acid and 3-hydroxybutyric acid, has been used in molar-scale preparation of enantiomerically pure sulfoxides methyl ( )-2-(phenylsulfinyl)acrylate and (K)-isopropenyl p-tolyl sulfoxide [107]. 

Chromium complexes (continued) organohalide activation, 5, 381 with phosphine-based supporting ligands, 5, 365 porphyrin-ligated derivatives, 5, 364 pyridinebis(imine) ligand derivatives, 5, 361 salen-ligated complexes, 5, 379 surface chemistry on oxides, 12, 525 tetradentate [04] compounds, 5, 352 tetradentate thioether derivatives, 5, 365 thiolate-bridged, Fe- and Rh complexes, 5, 308 with Ti(IV), 4, 627... 

Bromobenzyl 2-fluorophenyl thioether, derived from 2-fluorothiophenol and 2-bromobenzyl bromide, is a source of a benzyne through reaction with /-butyllithium. Simultaneously, the bromobenzyl moiety generates the tethered aryllithium 405 and an intramolecular anionic cyclisation is promoted. The sequence is completed by the addition of an electrophilic species leading to 1-substituted b/Z-dibenzol //]thiopyrans (Scheme 121) <2002CEJ2034>. 

PET cyclizations of donors-substituted phenylgloxylates have been intensively studied by the groups of Neckers and Hasegawa. For the thioether derivatives 1 the efficiency of the cyclization depended on the linker chain length (Sch. 5) [18]. With increasing carbon tether (>7 = 2-10) the yield dropped steadily and secondary reductive dimerizations or Norrish Type II processes became competitive. Consequently, the Cn-linked substrate solely underwent dimerization and cleavage [18b]. 

In order to find a synthetic route to diphenyl thioether derivatives of peptides and amino acids, the reaction of iodinated aryl amino acid, such as monoiodo (O-methyl) Boc-tyrosine methyl ester (214) with Boc-protected / -mercaptophenylalanine methyl ester (215) (R=Me), or the free acid (215, R = H) was studied in liquid ammonia, 90% yield of 216 from 215, R = Me were obtained (equation 149)281. 

Immunochemical detection of quinol-thioether-derived protein adducts. Chem. Res. Toxicol. 11 1283-1290... 

An indium-mediated ring-expansion reaction of a cyclic thioether derivative 31 in aqueous medium leads to the eight-membered cyclic thioether derivative 32, which isomerizes to the more stable conjugated product 33 in 62% yield (referred to 31) (Scheme 10) <1999SL735>. For a review of such Barbier-Grignard type reactions in water see <1996T5643>. 

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