Sulfoxide, dimethyl ylide from

Methylene triphenylarsorane (//, 31, 34, 39) has been prepared in situ from the salt in ether (34, 39), benzene (34, 39, 60), tetrahydrofuran (31), or dimethyl sulfoxide (II) by reaction with butyl- or phenyllithium (34, 39), sodium hydride (31), methylsulfinylcarbanion (II), or sodamide (102). Ethylidene triphenylarsorane has been prepared by reaction with methylsulfinylcarbanion (II) whereas fluorenylidene-(9)-trimethyl- and fluor-enylidene-(9)-dimethylbenzylarsorane (101) have been made using phenyllithium in ether. Sodium methoxide in methanol has been used successfully (41, 47, 48, 94) to generate ylides from their corresponding salts when R is an electron-withdrawing group (e.g., COOR, COR, or CN). 

Ylides based upon sulfur are the most generally useful in these cyclopropane-forming reactions.133 Early work in this area was done with the simple dimethyloxysulfonium methylide (9) derived from dimethyl sulfoxide. The even simpler dimethylsulfonium methylide (10) was studied at the same time as a reagent primarily for the conversion of carbonyl compounds into epoxides.134 Somewhat later, other types of sulfur ylides were developed, among which the nitrogen-substituted derivatives such as (11) are... 

Dimethyl sulfoxide (DMSO) can be used for carbon-carbon bond formation and as a precursor for the synthesis of stabilised sulfur ylides (see Chapter 3, p. 33). The sulfoxy S=0 group, like the sulfone (S02) group, has a stabilising effect on an adjacent carbanion hence, sulfinyl carbanions, like sulfonyl carbanions (see Chapter 10, p. 200), are useful reagents in organic synthesis. The carbanions (39) derived from alkylthioalkyl sulfoxides (38) are particularly valuable intermediates in syntheses (Scheme 21). 

Cyclopropanated 1,3-disubstituted 1,2-dihydropentalenes 12 were prepared from 1,2-di-hydropen talenes 11 by methylene transfer from trimethyloxosulfonium iodide in dimethyl sulfoxide using sodium hydride at room temperature. The phenyl substituent at Cl completely shields the ryn-side of the reactive C3 to C4 double bond against attack by the ylide reagent. Compounds 12 serve as starting materials for hexahydroindene derivatives by acid-catalyzed ring-expansion reactions. 

The initial asymmetric synthesis (see Scheme 5.2) of pyrrolidine acid 3 suffered from a chiral HPLC bottleneck. As a result, chiral salt resolution was investigated. The rapid discovery of a crystalline di-p-toluoyl-D-tartaric acid salt provided the necessary means to resolve and purify the desired diastereomer. Using 0.65 equivalent of the acid in methyl (cr(-butyl ether (MTBE), the crystallized salt was shown to be a 92 8 ratio of (3S,4R) (3R,4S) diastereomers. The resolved tartaric acid salts were then recrystalhzed from n-butanol to ratios of >99 1 in a 42% overall yield on a 2-kg scale. Further improvements were made in the preparation of the azomethine ylide precursor 38. In step 1, using dimethyl sulfoxide (DMSO) as the solvent, the reaction temperature of trimethylsilylmethylation of tert-butylamine was lowered from 200°C used in the original synthesis to 80°C. In step 2, substituting n-butanol in place of methanol reduced the amount of oligomerization observed and increased the yield to 69%. Overall, these improvements allowed for the preparation of pyrrolidine acid 3 in 22% overall yield in 99% ee from cinnamate 39 (Scheme... 

The mechanism of the Swem oxidation has been studied in depth and the formation of an initial adduct 7 from the reaction between dimethyl sulfoxide and oxalyl chloride which then collapses to give a dimethylchlorosulfonium species 8 is clearly indicated by mechanistic studies.3,8 Reaction of 8 with an alcohol then produces the alkyoxysulfonium ion 9 which upon treatment with an amine base gives the ylide 10. Subsequent proton extraction gives the carbonyl product 2 with the release of dimethyl sulfide. 

Of the various methods of preparing phosphorus ylides, that much preferred — apart from a few exceptions — is the action of bases on phosphonium salts. The strength of the base is adjusted to the acidity of the phosphonium salt bases used have been carbon bases such as butyl- and phenyllithium, nitrogen bases such as sodamide, lithium diethylamide, and 1,5-diazabicyclo-[4.3.0]non-5-ene, and oxygen bases such as sodium hydroxide and potassium alkoxides. The pairs dimethylsulfoxide-sodium hydride1000 and dimethyl sulfoxide-potassium terf-butoxide1001 have proved particularly valuable. 

The same ylide was used by Isler and his collaborators1013 for synthesis of polyene carboxylic acids. / ,y-Unsaturated carboxylic acids are accessible by starting from (2-ethoxycarbonylethyl)triphenylphosphonium chloride1014 and, e.g., cyclohexanone1015 in dimethyl sulfoxide-tetrahydrofuran containing sodium hydride ... 

NaH stirred ca. 45 min. at 65-70° under Ng in excess dimethyl sulfoxide until Hg-evolution is complete, allowed to react with 1 equivalent of ethyl triphenyl-phosphonium bromide, then with 0.85 equivalent of benzophenone 1,1-di-phenyl-l-propene. Y 97.5%.—The reactivity of the methylsulfinyl carbanion (formed by reaction of NaH with dimethyl sulfoxide), which is even more basic than the trityl anion, is sufficient to convert phosphonium salts into ylides thereby permitting a simple and convenient modification of the Wittig reaction. E. J. Gorey and M. Ghaykowsky, Am. Soc. 8A, 866 (1962) / -diketones from carboxylic acid esters and ketones (s. Synth. Meth. 6, 737), sym. ) -diketones, s. J. J. Bloomfield, J. Org. Chem. 27, 2742 (1962). 

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