Dimsyl anion reactions

The most general methods for the syntheses of 1,2-difunctional molecules are based on the oxidation of carbon-carbon multiple bonds (p. 117) and the opening of oxiranes by hetero atoms (p. 123fl.). There exist, however, also a few useful reactions in which an a - and a d -synthon or two r -synthons are combined. The classical polar reaction is the addition of cyanide anion to carbonyl groups, which leads to a-hydroxynitriles (cyanohydrins). It is used, for example, in Strecker s synthesis of amino acids and in the homologization of monosaccharides. The ff-hydroxy group of a nitrile can be easily substituted by various nucleophiles, the nitrile can be solvolyzed or reduced. Therefore a large variety of terminal difunctional molecules with one additional carbon atom can be made. Equally versatile are a-methylsulfinyl ketones (H.G. Hauthal, 1971 T. Durst, 1979 O. DeLucchi, 1991), which are available from acid chlorides or esters and the dimsyl anion. Carbanions of these compounds can also be used for the synthesis of 1,4-dicarbonyl compounds (p. 65f.). 

Corey and Chaykovsky were the first to investigate the reaction of dimethyl sulphoxide anion (dimsyl anion) with aldehydes and ketones400,401. They found that the reaction with non-enolizable carbonyl compounds results in the formation of /1-hydroxyalkyl sulphoxides in good yields (e.g. Ph2CO—86%, PhCHO—50%). However, with enolizable carbonyl compounds, particularly with cycloalkanones, poor yields of hydroxyalkyl products are observed (e.g. camphor—28%, cyclohexanone—17%, but... 

In this way benzalaniline reacts with dimsyl anion to give /J-anilinosulphoxide 446 in 92% yield401 (equation 267). Nudelman and Cram have found that the analogous reaction with the carbanion of benzyl p-tolyl sulphoxide is more complex and leads to the formation of substituted cyclopropyl sulphoxides 447 (equation 268)522. The carbanion derived from cyclohexanone dimethyldithioacetal S-oxide 448 gives /J-mercaptoanilines derivatives on treatment with iminoketones and further elaboration523 (equation 269). 

The first reports on this reaction were published almost simultaneously by Russell and coworkers533 and Corey and Chaykovsky534, who reacted dimsyl anion with a variety of carboxylic esters and obtained the corresponding a-ketosulphoxides 464 in high yields (equation 277 Table 25). 

TABLE 25. Reaction of dimsyl anion with carboxylic esters... 

Reaction of dimsyl anion with isothiocyanates gives a-thioamidosulphoxides 478 in 12-59% yield, whereas with isocyanates it affords a mixture of a-amidosulphoxides 479 and methylsulphinylmalonoamides 480, the products of a double addition549 (equation 289). 

In contrast, a-ketosulphoxides react with isocyanates to give the products of a monoaddition only550 (equation 290). Reaction of dimsyl anion with trithiocarbonates 481 followed by alkylation results in the formation of (methylsulphinyl)ketene dithio-acetals 482551 (equation 291). 

Dimsyl anion 88 is known to add to styrene, and to 1,1-diphenylethylene in the presence of a base, forming 3-arylpropyl methyl sulfoxides121. Treatment of ( )-3,3-dimethyl thiacyclo-oct-4-ene-l-oxide 89 with n-BuLi gave exo-4,4-dimethyl-2-thiacyclo-[3.3.0]octane 2-oxide 90, a bicyclic addition product of the internal double bond. A similar cyclization was observed in the reaction of 91 with n-BuLi122. 

An interesting reaction of dimsyl anion 88 is the methylation of polyaromatic compounds. Thus naphthalene, anthracene, phenanthrene, acridine, quinoline, isoquinoline and phenanthridine were regiospecifically methylated upon treatment with potassium t-butoxide and DMSO in digyme or with sodium hydride in DMSO123-125. Since ca. 50% of D was found to remain in the monomethyl derivative 93 derived from 9-deuteriophenanthrene 92, the mechanistic route shown in Scheme 2 was suggested125. 

Dimsyl anion 88 reacts with esters of aromatic carboxylic acids and aliphatic acids which do not have a readily transferable proton, to give /5-ketosulfoxides114,133,138-141. There are not many cases in which acyl chlorides were used142,143. However, the reaction... 

Corey and Chaykovsky114 found that the dimsyl anion reacts with benzophenone and benzaldehyde to afford the corresponding /S-hydroxysulfoxides 109 and 110. Thermal decomposition of these j3-hydroxysulfoxides was shown to give a, )3-unsaturated sulfoxides155 or olefins156,157. Thus, the reaction of dimsyl anion with benzophenone at 100 °C gave 1,1-diphenylethylene, diphenylmethane, 1,1-diphenylcyclopropane and diphenylacetaldehyde, besides 1, l-diphenyl-2-methylthioethylene156,157. 

Dihydrodithiin sulphoxides, synthesis of 243 Dihydrothiophene dioxides, reactions of 653 /(,/( -Dihydroxyketones 619 Dimerization, photochemical 877, 884 Dimethyl sulphoxide anion of - see Dimsyl anion hydrogen bonding with alcohols and phenols 546-552 oxidation of 981, 988 photolysis of 873, 874, 988 radiolysis of 890-909, 1054, 1055 self-association of 544-546 Dimsyl anion... 

Polyaromatic compounds, reaction with dimsyl anion 607... 

Chlorodiphenylphosphine 488 reacts with a-sulphinyl carbanions to give a-sulphinylphosphines 489 which undergo ready isomerization to a-sulphenylphosphine oxides 4W (equation 295). The report of Almog and Weissman that a-sulphinyl carbanions react with phosphorochloridates 491 to give a-phosphoryl sulphoxides 492 calls for correction (equation 296). Actually, the phosphorylation occurs at the oxygen atom of the ambident dimsyl anion, and is followed by the Pummerer-type reaction affording diethylphosphoric acid and tetraethyl pyrophosphate among other products . ... 

Dimsyl anion fails to undergo SrnI reactions with aryl halides,134,143 and the occurrence of fragmentation processes similar to those in equations (11) and (45) have been used to explain this failure,143 correcting the earlier, falacious claim that dimsyl anion and halobenzenes react to give benzyl methyl sulfoxide in high yield.144... 

Table 4.4 lists some common bases used in organic chemistry. Although butyl-lithium behaves as a very strong base in many reactions, it also exhibits other chemistry, so it is usually used to prepare other strong bases listed in the table. Lithium diisopropylamide, sodium amide, dimsyl anion, and sodium hydride are often used to prepare the conjugate bases of aldehydes, ketones, and esters for use in reactions. Potassium fert-butoxide is employed when a base somewhat stronger than the conjugate bases of most alcohols is needed. 

The strongest base that can be used in any particular solvent is the conjugate base of that solvent. Any stronger base will simply react to produce the conjugate base of the solvent. For this reason a base is often used in its conjugate acid as the solvent. For example, NH2 is often used in liquid NH3 as the solvent (NH3 boils at —33°C. so the reaction must be done at low temperature), OH- is often used in water as the solvent, ethoxide ion (CH3CH20 ) is often used in ethanol (CH3CH2OH) as the solvent, and the dimsyl anion is often used in DMSO as the solvent ... 

Perturbation Molecular Orbital (PMO) theory has been used to account for the regioselectivity of the reaction of naphthyridines (l)-(6) with amide and dimsyl anions. The reaction with the amide ion (a hard nucleophile) is under charge control, whereas the reaction with the dimsyl ion (a soft nucleophile) is determined by the distribution of the LUMO <91PJC1449>. 

The use of DMSO in recent studies has been largely upon the premise that the problem of base association would be avoided. Some doubt as to the validity of this assumption arises when the results of a conductometric study are considered (Exner and Steiner, 1974). Ion-pairing constants for lithium, sodium, potassium and cesium t-butoxide in DMSO have been evaluated as 108, 106, 270 and 200 M-1 respectively. Not only do these results suggest that there is base association in DMSO but they also imply that base-catalysed reactions involving alkali metal alkoxides in DMSO should be affected by the nature of the cation. If these conclusions are valid and if the possible involvement of the dimsyl anion in these reactions is also taken into consideration, then the choice of DMSO to remove the problem of base association can be a poor one, especially if the base is a lithium or sodium salt of a hindered alkoxide. It is far better to avoid association effects by the use of crown ethers (Bartsch et al., 1973, 1974, 1975). On the other hand, the use of lithium and potassium t-butoxide in DMSO solvent might aid in distinguishing reactivities of free ions and of ion pairs in certain processes. 

The use of pure dimethyl sulfoxide with alkoxide (CH3O , tert-C4 l O ) or hydride (H ) ions leads to even more strongly basic systems which contain, in part, the very strongly basic dime-thylsulfinyl ( dimsyl ) anion, formed in the following equilibrium reaction ... 

Phosphorus ylids are prepared by treatment of phosphonium salts with bases such as phenyllithium, butyllithium. dimsyl anion, or potassium f-butoxide. They are not isolated but used directly after preparation because they are sensitive to oxygen and moisture. The requisite phosphonium salts are available in great variety from the reaction of triphenylphosphine and primary or secondary alkyl halides, usually bromides [24]. 

Treatment of ketone 93 with dimsyl anion generates enolate 94, but this can potentially form a mixture of E)- and (Z)-isomers. Reaction of 94 with various alkyl halides led to the 0-alkylation product (95) and the C-alkylation product (96). In DMSO, the ratio of O- to C-alkylation is relatively insensitive to changes in the gegenion (the metal), suggesting that the enolate is an unencumbered anion in this cation solvating medium. Note that C-alkylation is preferred except when the steric bulk at the nucleophilic carbon becomes too great (R, = Ph, Ph or Et, Et). For PhCOCHPh2 (93, r1 = r2 = Ph), O-alkylation is effectively the only process. 

---