Dimethylsulfoxonium methylide

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). 

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). 

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. ... 

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. ... 

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. 

Sulfur ylides have several applications as reagents in synthesis.282 Dimethylsul-fonium methylide and dimethylsulfoxonium methylide are particularly useful.283 These sulfur ylides are prepared by deprotonation of the corresponding sulfonium salts, both of which are commercially available. 

Whereas phosphonium ylides normally react with carbonyl compounds to give alkenes, dimethylsulfonium methylide and dimethylsulfoxonium methylide yield epoxides. Instead of a four-center elimination, the adducts from the sulfur ylides undergo intramolecular displacement of the sulfur substituent by oxygen. In this reaction, the sulfur substituent serves both to promote anion formation and as the leaving group. 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

With the more stable dimethylsulfoxonium methylide, the reversal is relatively more rapid and product formation takes place only after conjugate addition. 

Another difference between dimethylsulfonium methylide and dimethylsulfoxonium methylide concerns the stereoselectivity in formation of epoxides from cyclohexanones. Dimethylsulfonium methylide usually adds from the axial direction whereas dimethylsulfoxonium methylide favors the equatorial direction. This result may also be due to reversibility of addition in the case of the sulfoxonium methylide.92 The product from the sulfonium ylide is the result the kinetic preference for axial addition by small nucleophiles (see Part A, Section 2.4.1.2). In the case of reversible addition of the sulfoxonium ylide, product structure is determined by the rate of displacement and this may be faster for the more stable epoxide. 

Examples of the use of dimethylsulfonium methylide and dimethylsulfoxonium methylide are listed in Scheme 2.21. Entries 1 to 5 are conversions of carbonyl compounds to epoxides. Entry 6 is an example of cyclopropanation with dimethyl sulfoxonium methylide. Entry 7 compares the stereochemistry of addition of dimethylsulfonium methylide to dimethylsulfoxonium methylide for nornborn-5-en-2-one. The product in Entry 8 was used in a synthesis of a-tocopherol (vitamin E). 

For the preparation of the benzo[fc]cyclopropa d pyran 2-599, Ohta and coworkers have treated 3-ethoxycarbonylcoumarin (2-597) with dimethylsulfoxonium methylide (2-598), derived from the corresponding trimethylsulfoxonium iodide and NaH (Scheme 2.136) [307]. The isolated product was not 2-599, however, but an unexpected eye lope nia[fc]benzofuran derivative 2-600 probably formed through 2-599. 

It was an interesting idea to create the giant tube-like structures 46 capped with a Lewis acid center by the homologation reaction of 42 with dimethylsulfoxonium methylide and their deboronation to the three-armed star polymethylene polymers 47 incorporating a m, r-l,3,5-trisubstituted cyclohexane core (Scheme 12) <2003JA12179, 20010L3063>. 

Spurred by these observations, we examined a relevant application of the method for nitrocyclopropane synthesis from nitroalkenes and dimethylsulfoxonium methylide (17), Equation 3. It had previously been employed for the synthesis of a 2,3-dideoxv-2,3-C-methylene-3-nitro-hexopyranoside, the first one of the small number of carhohvdrates containing the nitrocyclopropane structure thus far known (18). 

Examples of the use of dimethylsulfoniurn methylide and dimethylsulfoxonium methylide in the preparation of epoxides are listed in Scheme 2.19. Entries 1-4 illustrate epoxide formation with simple aldehydes and ketones. 

An unusual type of dipolar cycloaddition is known to occur to 2//-dihydrooxazine 180 when it is treated with dimethylsulfoxonium methylide 181 (Scheme 16) <1994CPB739>. Ring contraction of the intermediate 182 results in formation of the oxazolidine-4,5-dione 183. 

Dimethylsulfoxonium methylide reacts normally with the ketone carbonyl of dibenz[6,e]azepine-5,11-diones to yield epoxides (116) (75JOC3602). 

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

EPOXIDES Dimethylsulfoxonium methylide. Hydrogen peroxide. Hydrogen pcroxide-Triethyl orthoacctatc. I crmonophosphoric acid. Silica gcL Trifluoromethanesulfonic anhydride. Triphenylarsonium ethylide. 

Synthesis of racemic naproxene Friedel-Crafts acylation (aluminum chloride - nitrobenzene) of p-naphthol methyl ether affords 2-acetyl-6-methoxy naphthalene, which, when treated with either dimethyl sulfonium or dimethylsulfoxonium methylide, gives 2-(6-methoxynaphthalen-2-yl)propylene oxide. Treatment of the latter with boron trifluoride etherate in tetrahydrofuran gives 2-(6-methoxynaphthalen-2-yl)propionaldehyde, which is oxidized using Jones reagent (4 M chromic acid) to yield the racemic 2-(6-methoxynaphthalen-2-yl)propionic acid. 

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