Sulfides unsymmetrical

An attractive route to chiral sulfoxides is based on asymmetric oxidation of unsymmetrical sulfides by means of chiral oxidizing reagents. The first asymmetric oxidation of sulfides with optically active pera-cids (eq. [1]) has been independently described in 1960 by two groups headed by Montanan (36) in Italy and by Balenovic (37) in... 

In contrast to asymmetric oxidation of unsymmetrical sulfides with chiral peracids, microbial oxidation usually gives much better results. Thus, optically active phenyl benzyl sulfoxide was prepared by oxidation of the parent sulfide via fermentation with Aspergillus niger, NRRL 337, with 18% optical purity (42). Similarly, asymmetric... 

Low asymmetric induction (e.e. 0.3-2.5%) was found (56) to occur when unsymmetrical sulfides were electrochemically oxidized on an anode modified by treatment with (->camphoric anhydride or (5)-phenylalanine methyl ester. 

More recently, sulfide oxidations with [hydroxy(tosyloxy)iodo]benzene (4, HTIB) have been reported [15]. Such reactions proceed readily in di-chloromethane at room temperature and stop at the sulfoxide stage (Scheme 2). HTIB can also be generated in situ from iodosylbenzene (5) and 10 mol% p-toluenesulfonic acid for catalytic oxidations of sulfides to sulfoxides [16]. Oxidations of unsymmetrical sulfides with the chiral (+)-10-camphorsulfonyloxy analog of HTIB afford the corresponding sulfoxides (82-92%) with low enan-tioselectivities (2.7-13.7% ee) [15]. 

Unsymmetrical sulfides 39 need the same disconnection we have just used for ethers. The anion 41 of a thiol 42 will combine with an alkyl halide 40 to make a new C-S bond. The reaction is much easier with sulfur. Thiols are more acidic than alcohols, just as H2S is more acidic than water. Sulfide anions 41 are more nucleophilic towards saturated carbon than are alkoxides and the risk of elimination is much less. 

Ginsburg, J. L., Darvesh, K. V., Axworthy, P., Langler, R. F. An ab initio molecular orbital study of sulfur-substituted carbanions toward an understanding of regiochemistry in the chlorination of unsymmetrical sulfides. Aust. J. Chem. 1997, 50, 517-521. 

In the presence of sodium hydroxide, thiols react with alkyl halides to form the sulfides (20) the reaction occurs via the sodium thiolate and is analogous to the well-known Williamson synthesis of ethers and can also be applied to obtain unsymmetrical sulfides (Scheme 18). Symmetrical sulfides may be prepared directly by condensation of sodium sulfide with alkyl halides (Scheme 18). These reactions are of the SN2 type, and consequently the optimum yields of sulfides are realised using primary alkyl halides. 

Alkylation or acylation of ketones, sulfides, and amines. This reagent generally reacts with alcohols or carboxylic acids to form 2,2,2-trifluoroethyl ethers or esters in satisfactory yields, except in the case of alcohols prone to dehydration. The reaction of these ethers provides a simple synthesis of unsymmetrical sulfides (equation I). A similar reaction can be used for preparation of secondary amines or amides (equation II). Enolate anions (generated from silyl enol ethers with KF) can be alkylated or acylated with a or b (equation III). Use of Grignard reagents in this type of coupling results in mediocre yields. 

AgSbFg catalysis to afford fhe corresponding unsymmetrical sulfides (Scheme... 

Oxidation of unsymmetrical sulfides, such as 125, to the corresponding optically active sulfoxides with CBT is high enantioselective, for example, in the synthesis of (S)-(-)-BOF-4272 126a, a xantine dehydrogenase inhibitor. Reaction proceeds in DMF in the presence of 4-cyanopyridine and a chiral alcohol (96TA2991) (Scheme 122). 

Cobalt(II) chloride. 14, 99 IS, 97-98 Allylation of 1,3-dicarbonyl comp motes the allylation of 1,3-dicarbonyl cc Unsymmetrical sulfides. RSH -P-Acetamido ketones. A three-ci an aldehyde, and acetonitrile appears 1 hydration of nitrilium species, which is 1... 

Sulfides. Symmetrical sulfides can be prepared in high yield from the reaction of alkyl halides and sodium sulfide in water with this phase-transfer catalyst. Unsymmetrical sulfides are prepared from alkyl halides and sodium mercap-tides. Secondary alkyl halides react more slowly than primary halides bromides are more reactive than chlorides. ... 

Unsymmetrical sulfides. Unsymmetrical sulfides can be prepared in 65-85% yield by reaction of sulfides with the sodium salts of alcohols in the presence of this aminophosphonium salt (equation I). The sulfuration proceeds with inversion of configuration (equation II). 

This section illustrates several specific transformations of organoboranes that are synthetically useful. The preparation of unsymmetrical sulfides is increasingly important since chiral sulfoxides can be prepared (sec. 

A variant of conventional Suzuki coupling is represented by the reaction of 9-organothio-9-borabicyclo[3.3.1]nonanes with organic electrophiles to form unsymmetrical sulfides. ... 

Table 4.9 Synthesis of Unsymmetrical Sulfides, Selenides, and Tellurides ...

Komori, T, and Nonaka, T., Electroorganic reactions on organic electrodes. 6. Electrochemical asymmetric oxidation of unsymmetric sulfides to the corresponding chiral sulfoxides on poly(amino acid)-coated electrodes, J. Am. Chem. Soc., 106, 2656 (1984). 

Unsymmetrical sulfides, RSR , are prepared by converting a thiol to a sodium salt with either sodium hydroxide or sodium ethoxide and then allowing the salt to react with a haloalkane. 

Symmetrical sulfides are created by reacting Na2S with two moles of haloalkane. Unsymmetrical sulfides are synthesized by reacting the sodium salt of a thiol with a haloalkane. 

To present, silica-supported rhodium catalysts have been successfully used for hydrogenation, hydroformylation, and hydrosilylation reactions. Zhang and coworkers" developed a heterogeneous rhodium complexes 23 catalyzed carbon-heteroatom bond formation. The reaction couples disulfides 21 or diselenides with an alkyl or acyl halide to generate unsymmetrical sulfides (24) and selenides in good yields. The catalyst could be easily recovered and recycled by filtration of the reaction solution and re-used for five cycles without significant loss of activity (maintains over 90% yield)." ... 

Removal of the TIPS group with TBAF or CsF in the presence of H2O led to the formation of thiol. Unsymmetrical sulfides can be formed when a suitable alkylating agent was used to trap the thiolate intermediate after addition of the fluoride source (eq 26). ... 

Unsymmetrical sulfides possessing carbonyl groups beta to sulfur have been prepared by Michael addition of thiols to a,i8-unsaturated aldehydes, ketones, and esters in tetrahydrofuran under phase transfer conditions [17] (see Eq. 13.8). This reaction is catalyzed by fluoride ion. In this application, tetrabutylammonium fluoride (TBAF)... 

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