Methylides

An interesting aspect of this reaction is the contrasting stereoselective behaviour of the dimethyisulfonium and dimethyloxosuifonium methylides in reactions with cyclic ketones (E.J. Corey, 1963 B, 1965 A C.E. Cook, 1968). The small, reactive dimethyisulfonium ylide prefers axial attack, but with the larger, less reactive oxosulfonium ylide only the thermodynamically favored equatorial addition is observed. 

Trimethylsulfoxonium iodide (11) is of interest because treatment with sodium hydride or dimsyl sodium produces dimethyl sulfoxonium methylide [5367-24-8] (12) (eq. 22), which is an excellent reagent for introducing a methylene group into a variety of stmctures (53) ... 

A convenient route to A -isoxazoline N-oxides has been developed from nitrostyrenes using dimethylsulfoxonium methylide. The addition of the ylide (572) to the nitrostyrene (571) was greatly facilitated by the presence of copper(I) salts, the isoxazoline N-oxide (573) being obtained in excellent yield (76JOC4033). 

Bravo et al. studied the reaction of various ylides with monooximes of biacetyl and benzil. Dimethylsulfonium methylide and triphenylarsonium methylide gave 2-isoxazolin-5-ol and isoxazoles, with the former being the major product. Triphenylphosphonium methylide and dimethyloxosulfonium methylide gave open-chain products (Scheme 135) (70TL3223, 72G395). The cycloaddition of benzonitrile oxide to enolic compounds produced 5-ethers which could be cleaved or dehydrated (Scheme 136) (70CJC467, 72NKK1452). 

Carbanions in the form of ylides also add to azirines. For example, treatment of 1-azirine (227) with dimethylsulfonium methylide gives 1-azabicyclobutane (229) in good yield (72JA2758). The addition of the methylene group occurs by initial nucleophilic attack by the ylide to give intermediate (228) which cyclizes with expulsion of dimethyl sulfide. 

Ring expansion of activated aziridines (43) with sulfur ylides also provides a synthesis of azetidines (75JOC2990, 58BSF345, 81CC417). The highly reactive sulfonium methylide (44 R = R = H) undergoes further reaction with the azetidines (46), but the reaction is satisfactory for substituted methylides. The less reactive sulfoxonium methylide (45 R = R = H)... 

Pyridinium bis(alkoxycarbonyl)methylides radical anions ESR, 2, 144 radical cations ESR, 2, 144... 

Although steroidal spiro oxiranes are difficult to obtain stereochemically pure by peracid epoxidations of exocyclic methylenes,the recently developed methylene transfer reagents, dimethylsulfonium methylide and di-methylsulfoxonium methylide in tetrahydrofuran, proved useful in the stereoselective transformation of steroid ketones to a- and -oxiranes, (87) and (88), respectively. ... 

Dimethylsulfonium methylide is less stereoselective than dimethylsul-foxonium methylide. 

Base-catalyzed proton abstraction from trimethylsulfoxonium halides (1) with formation of dimethylsufoxonium methylide (2) was described by Corey in 1962. Solutions of (2) in dimethyl sulfoxide are conveniently prepared from the chloride or iodide (1) by stirring with one equivalent of sodium hydride at room temperature. 

In the presence of suitable a,/5-unsaturated carbonyl compounds (3) the nucleophilic methylide (2) undergoes conjugate addition followed by expulsion of dimethyl sulfoxide to give cyclopropanes (5). 

Addition of dimethylsulfoxonium methylide to the a-face of A -20-ketones, A -5a-H-ketones and A " -3-ketones results in the formation of the corresponding 16a,17a-methylene (1), la,2a-methylene-5a-H (2) and la,2a-methylene-A" steroids (3), respectively. Smooth reaction is also observed in the presence of 2-chloro and 2-bromo substituents in the A -5a-H-3-ketone series.Yields of 90% are obtained within a reaction period of 5 hr at room temperature. A A -3-keto system in (1) is not attacked under these conditions. 

Under the conditions of the Corey reaction quarternary Mannich bases (10) would be expected to undergo /9-elimination to the unsaturated ketones (12) which could then react in situ with dimethylsulfoxonium methylide (11) to give the a,of-ethylene ketones (13). 

Thus a 1 1 mixture of 6a,7a- and 6/9,7/9-methylene adducts is obtained from 17/6-hydroxyandrosta-4,6-dien-3-one (17) or its acetate and dimethylsul-foxoniiim methylide. 

Similar results are obtained by reaction of 6-chloropregna-4,6-diene-3,20-dione with dimethylsulfoxonium methylide. In this case a 2 1 mixture of 6a,7a-methylene and 6) ,7 -methylene adducts is obtained. 

Addition of dimethylsulfoxonium methylide has also been studied in the retro steroid (9, 10a) series. Results are somewhat different from observations in the normal series. Thus only the 6, 7)3-methylene adduct is obtained from a 4,6-dien-3-one while 6-chloro-9) ,10a-l,4,6-trien-3-ones undergo attack at the 6,7-double bond in preference to the 1,2-double bond resulting in the formation of 6a-chloro-6)5,7i5-methylene-A -3-ones. ... 

Dimethyl-5a-cholestan-3-one, 92 Dimethylmagnesium, 86 Dimethylsulfonium methylide, 18, 113 Dioxane dibromide, 220... 

Another triflate ester that recently has found growing application in organic synthesis is commercially available trimethylsilylmethyl trifluoromethanesul fonate. This powerful alkylating reagent can be used for the synthesis of various methylides by an alkylation-desilylation sequence A representative example is the generation and subsequent trapping by 1,3-dipolar cycloaddition of indolium methanides from the corresponding indole derivatives and trimethylsilylmethyl trifluoromethanesulfonate [108] (equation 54)... 

Thus Ph3P=CH2 is triphenylphosphonium methylide (see pp. 274-304 of reference 2, or textbooks of organic chemistry for a fuller treatment of the Wittig reaction). 

The Corey-Chaykovsky reaction entails the reaction of a sulfur ylide, either dimethylsulfoxonium methylide (1, Corey s ylide, sometimes known as DMSY) or dimethylsulfonium methylide (2), with electrophile 3 such as carbonyl, olefin, imine, or thiocarbonyl, to offer 4 as the corresponding epoxide, cyclopropane, aziridine, or thiirane. ... 

Dimethylsulfoxonium methylide (1) is the reagent of choice for the cyclopropanation of a,p-unsaturated carbonyl substrates. The reaction is generally carried out at more elevated temperatures in comparison to that of 2, although exceptions exist. The method works for 0 ,P-unsaturated ketones, esters and amides. Representative examples are found in transformations of 2(5//)-furanone 55 to cyclopropane 56 and 0 ,P-unsaturated Weinreb amide 57 to cyclopropane 58. ... 

In the initial report by Corey and Chaykovsky, dimethylsulfonium methylide (2) reacted smoothly with benzalaniline to provide an entry to 1,2-diphenylaziridine 67. Franzen and Driesen reported the same reaction with 81% yield for 67. In another example, benzylidene-phenylamine reacted with 2 to produce l-(p-methoxyphenyl)-2-phenylaziridine in 71% yield. The same reaction was also carried out using phase-transfer catalysis conditions.Thus aziridine 68 could be generated consistently in good yield (80-94%). Recently, more complex sulfur ylides have been employed to make more functionalized aziridines, as depicted by the reaction between A -sulfonylimine 69 with diphenylsulfonium 3-(trimethylsilyl)propargylide (70) to afford aziridine 71, along with desilylated aziridine 72. ... 

C-Methylation products, o-nitrotoluene and p-nitrotoluene, were obtained when nitrobenzene was treated with dimethylsulfoxonium methylide (I)." The ratio for the ortho and para-methylation products was about 10-15 1 for the aromatic nucleophilic substitution reaction. The reaction appeared to proceed via the single-electron transfer (SET) mechanism according to ESR studies. 

Treatment of trimethyloxosulfonium iodide with sodium hydride generates dimethyloxosulfonium methylide according to the reaction. This reagent has the remarkable... 

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