Sulphoxides Ketosulphoxides

The addition of sulphinyl chlorides to trimethylsilyl enol ether 138 affording a-ketosulphoxides 139 (equation 76) represents an extension of the reaction of sulphinyl chlorides with ketones. This reaction has attracted attention only recently. Sergeev and coworkers192 reported that treatment of sulphinyl chlorides with acyclic enol ethers afforded a-ketosulphoxides 139 in good to excellent yields. Meanwell and Johnson193 observed that in the case of cyclic enol ethers the corresponding sulphoxides were formed only in very low yields. They found, however, that the introduction of an equivalent amount of a Lewis acid into the reaction mixture markedly promotes the desired reaction, whereas the use of catalytic amounts of a Lewis acid led to a substantial reduction in the yield. This is most probably due to the formation of a complex, between the a-ketosulphoxide and the Lewis acid. 

It is well known that spontaneous resolution of a racemate may occur upon crystallization if a chiral molecule crystallizes as a conglomerate. With regard to sulphoxides, this phenomenon was observed for the first time in the case of methyl p-tolyl sulphoxide269. The optical rotation of a partially resolved sulphoxide (via /J-cyclodextrin inclusion complexes) was found to increase from [a]589 = + 11.5° (e.e. 8.1%) to [a]589 = +100.8 (e.e. 71.5%) after four fractional crystallizations from light petroleum ether. Later on, few optically active ketosulphoxides of low optical purity were converted into the pure enantiomers by fractional crystallization from ethyl ether-hexane270. This resolution by crystallization was also successful for racemic benzyl p-tolyl sulphoxide and t-butyl phenyl sulphoxide271. 

The preparation of enantiomerically enriched a-ketosulphoxides 272 was also based on a kinetic resolution involving the reaction of the carbanion 273 derived from racemic aryl methyl sulphoxides with a deficiency of optically active carboxylic esters 274334, (equation 151). The degree of stereoselectivity in this reaction is strongly dependent on the nature of both the group R and the chiral residue R in 274. Thus, the a-ketosulphoxide formed in the reaction with menthyl esters had an optical yield of 1.3% for R = Et. In the... 

Optically active a-ketosulphoxides 465 have also been obtained in this way starting from the carbanion derived from optically active sulphoxide 449537,538 (equation 278). 

In the reduction of racemic /i-ketosulphoxides (e.g. 464a) with actively fermenting yeast (Saccharomyces cerevisiae) the enantiomers are reduced at sufficiently different rates to allow isolation of optically active /1-hydroxy sulphoxide 524 and unreacted optically active /1-ketosulphoxide with at least 95% optical purity617,618 (equation 323). 

Sulphonylthioureas, mass spectra of 158 Sulphoxides - see also Alkoxysulphoxides, Aminosulphoxides, -Anilinosulphoxides, Cyanosulphoxides, a, /i-Dihalosulphoxides, Disulphoxides, Enaminosulphoxides, Episulphoxides, Epoxysulphoxides, Halosulphoxides, Hydroxysulphoxides, /i-Iminosulphoxides, Ketosulphoxides, a-Lithiosulphoxides, /i-Oximinosulphoxides, Persulphoxides, a-Thioamidosulphoxides addition reaction of 619-623, 836-845 aliphatic - see Aliphatic sulphoxides alkenyl - see Alkenyl sulphoxides alkyl aryl - see Alkyl aryl sulphoxides /(-alkylthio(arylthio)ethyl - see /J-Alkylthio(arylthio)ethyl sulphoxides... 

Acylation of oc-sulphinyl carbanions. Synthesis of fS-oxosulphoxides. oi-Ketosulphoxides have found very broad application in organic synthesis (see, for example. Reference 532). For this reason, a great deal of examples of their syntheses appear in the chemical literature. The main approach to this class of functionalized sulphoxides involves the reaction of a-sulphinyl carbanions with carboxylic esters or acyl halides. 

Nucleophilic addition to allenyl sulphoxides 547 proceeds across the a, /(-double bond to produce the corresponding )3-substituted allylic sulphoxides which undergo readily a [2,3]-sigmatropic rearrangement affording substituted allyl alcohols (equation 345). Under proper basic conditions, the initially formed allylic sulphoxides can rearrange to the corresponding vinyl sulphoxides which can be elaborated to 2,4-dienones 549 (equation 346) and a-ketosulphoxides (equation 347) . ... 

The chiral sulphoxide, (S)-(+)-2-(4-tolylsulphinyl)-2-cyclopentenone, has been used as a ring D component to effect an asymmetric Michael addition with 91-94% diastereoselectivity by reaction in the chelated form with the a,a-disubstituted lithium enolate from 2-bromo-6-methoxytetral-1-one while the (R)-(-) antipode reacts in a non-chelated form with the a-monosubstituted lithium enolate of 6-methoxytetralone (ref. 147). This synthesis makes use of earlier experience in the use of a-mono and a,a-disubstituted lithium enolates in the ethyl acetoacetate series with the non-chelated and chelated forms respectively of a p-ketosulphoxide (ref. 148). Eight futher steps were involved to produce (+)-estrone methyl ether in an overall yield of 6.3%. 

A ready route to j8-acylacrylic esters has been described, entailing alkylation of jS-keto-sulphoxides with bromoacetate followed by thermal sulphoxide elimination. The intermediate j8-ketosulphoxide esters may be reduced with sodium borohydride to the corresponding -hydroxysulphoxide esters which in turn may be converted into both y-hydroxy-ajS-unsaturated esters or a -butenolides. 

Acyclic Alditols.- A new approach to the synthesis of optically pure polyhydroxylated compounds by i) the stereospecific reduction of chiral -ketosulphoxides and ii) the stereospecific liydroxylation of chiral allylic /9-hydroxysulphoxides has been described. Thus the unsaturated ester (1) gave the chiral sulphoxide (2), which was sequentially reduced, hydtoxylated, and further reduced as outlined in Scheme 1 to give the L-arabinitol derivative (3) and hence penta-0-acetyl-L-arabinitol in high yield enantiomers are available by appropriate choice of the sulphoxide reagent. ... 

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