Reduction of the C-S bond

Correspondingly, p-chlorothiophenol produced a reduction of the C-S-bond with formation of the pyrrolidino 3,3,3-trifluoropropionitrile, a derivative of alanine. 

It is important to emphasize that the hydroxy dithioketal cyclization can be conducted under mild reaction conditions and can be successfully applied to a variety of substrates.15 However, the utility of this method for the synthesis of didehydrooxocane-contain-ing natural products requires the diastereoselective, reductive removal of the ethylthio group. Gratifyingly, treatment of 13 with triphenyltin hydride and a catalytic amount of the radical initiator, azobisisobutyronitrile (AIBN), accomplishes a homolytic cleavage of the C-S bond and furnishes didehydrooxocane 14 in diastereo-merically pure form (95 % yield), after hydrogen atom transfer. 

An attractive alternative to these novel aminoalcohol type modifiers is the use of 1-(1-naphthyl)ethylamine (NEA, Fig. 5) and derivatives thereof as chiral modifiers [45-47]. Trace quantities of (R)- or (S)-l-(l-naphthyl)ethylamine induce up to 82% ee in the hydrogenation of ethyl pyruvate over Pt/alumina. Note that naphthylethylamine is only a precursor of the actual modifier, which is formed in situ by reductive alkylation of NEA with the reactant ethyl pyruvate. This transformation (Fig. 5), which proceeds via imine formation and subsequent reduction of the C=N bond, is highly diastereoselective (d.e. >95%). Reductive alkylation of NEA with different aldehydes or ketones provides easy access to a variety of related modifiers [47]. The enantioselection occurring with the modifiers derived from NEA could be rationalized with the same strategy of molecular modelling as demonstrated for the Pt-cinchona system. 

The progress on S-C bond activation, which covers the reduction of a C-S bond to a C-H bond, cross coupling reaction of sulfides with main group organometaUic nucleophiles, ring opening reactions of thietanes and thiiranes, and desulfurization of thiols, sulfides, and thiophenes has already been reviewed elsewhere [6-10], and... 

As we have seen, reviewing catalytic S-X bond activations, some reactions complete their catalytic cycles by C-S bond-forming reductive elimination from C-M-S complexes. Hartwig et al. have reported on the mechanism of the C-S bond-forming reductive elimination from Pd(L)(R)(SR ) 122 (Eq. 7.72) [69]. 

Let us consider the general trends of the reactivity of C-C, C-S, and C-Q (Q = Cl, Br, I) bonds towards oxidative addition and reductive elimination (Scheme 7-25). In many cases, either C-C bond-forming reductive elimination from a metal center (a) or the oxidative addition of a C-Q bond to a low-valent metal center is a thermodynamically favorable process (c). On the other hand, the thermodynamics of the C-S bond oxidative addition and reductive elimination (b) lies in between these two cases. In other words, one could more easily control the reaction course by the modulation of metal, ligand, and reactant Further progress for better understanding of S-X bond activation will be achieved by thorough stoichiometric investigations and computational studies. 

The reduction of sulfides bearing a vic-OH group involves a fast cleavage of the C—S bond accompanied by a simultaneous elimination of the hydroxyl group. This process can be efficiently used as a mild method to create double bonds, for example, from ketones [209-211]. The yields of such a process are fairly high (Scheme 44). 

Catalytic hydrogenation of 1,4-thiazines is shown in Scheme 18. Both partial and complete hydrogenation of 54 has been performed successfully <1992JA4307>, but 2/7-1,4-thiazines 108, 198, and 199 underwent reductive cleavage of the C-S bond followed by cyclization to form a five-membered ring under similar conditions <1968G488>. 

As all of the direct extraction rates were low relative to the hydrogenative HDS rates, even at low conversions, the fully saturated compound dimethyl-cyclohexylcyclohexane was observed in the product mixture. As discussed in later sections, this fact indicates that the major cause of rate reduction by adjoining alkyl substituents may not be due to lowering adsorption constants but could well be due to steric limitations in the oxidative addition of the C-S bond to the catalytic site, as discussed later. A more subtle explanation could be adsorption-disguised kinetics whereby the intermediate is not released from the catalyst surface but remains adsorbed so that further conversion proceeds. This was not observed for unsubstituted diben-zothiophenes, however. 

His group [312,313] has done important work on the reductive cleavage of the C-S bonds of phenyl thioethers. These workers have shown the potential of two radical anions lithium p,p -di-t-butylbiphenylide (LDBB) and lithium l-(dimethylamino)naphthalenide (LDMAN) as reducing species. 

Many other uses of a-sulfinyl carbanions are found in the literature, and in the recent past the trend has been to take advantage of the chirality of the sulfoxide group in asymmetric synthesis. Various ways of preparation of enantiopure sulfoxides have been devised (see Section 2.6.2) the carbanions derived from these compounds were added to carbonyl compounds, nitriles, imines or Michael acceptors to yield, ultimately, with high e.e. values, optically active alcohols, amines, ethers, epoxides, lactones, after elimination at an appropriate stage of the sulfoxide group. Such an elimination could be achieved by pyrolysis, Raney nickel or nickel boride desulfurization, reduction, or displacement of the C-S bond, as in the lactone synthesis reported by Casey [388]. 

Review. Use of C8K as a heterogeneous reagent in organic synthesis has been reviewed, particularly as a reducing agent for C=C and C—N bonds, and for reductive cleavage of the C—S bond of a,p-unsaturated sulfones. C8K has been used to obtain active metals dispersed on graphite by reduction of metal halides. 

These conditions are fulfilled for the reduction of phenacylsulpho-nium salts at low pH values cleavage of the C—S bond occurs in the first step and proton transfer is involved only in the consecutive steps. The observed shift of half-wave potentials (74) with pH follows the plot predicted by equation (27). The intersection of the two linear parts indicates that phenacylsulphonium salts are moderately strong acids with pK values between 7 and 8 (Fig. 20). Potentiometrically measured pK values, used for verification, are in good agreement with the approximate pK values obtained from polarographic data. The system involved in the first step can be described by scheme (28) ... 

We tried to synthesize the carbon analogs of 14 and 12 by reductive cleavage of C-S bonds. The isolated products indicate, that 50 % of the C-S bonds were cleaved by electron transfer reactions and 50 % by LiSPh-elimination, probably after a H,Li-exchange (Scheme 6). 

Because of the importance of the sulfone moiety in organic synthesis as an activating group and the need, therefore, for its facile subsequent removal, it is no surprise that much more attention has been paid to methods of reductively cleaving the C—S bond in sulfones. Many such methods are available and they have been thoroughly examined in the recent review by Grossert. They will not be discussed further here. 

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