Cyclopropyl sulfoxides

A solution of dimethyloxosulfonium methylide in DMSO (30 ml) was prepared under argon from trimethyloxosulfonium iodide (9.6 mmol) and NaH (60% dispersion in oil, 9.6 mmol) at room temperature. After stirring for 90 min (the evolution of hydrogen ceased) the solution of the ylide was added dropwise to a solution of the vinyl sulfoxide (3.2 mmol) in DMSO (25 ml) over a 30 min period. The reaction mixture was stirred at room temperature for 14h, poured into an ice water mixture, and extracted twice with ether. The ether layers were washed twice with water, dried over anhydrous MgS04 and evaporated in vacuo to give a crude cyclopropyl sulfoxide as a white solid. Flash chromatography (silica, ethyl acetate/n-hexane (25 75) gave the (7 c,Ss) isomer (1.02g, 82%), m.p. 227-228°C and the (Sc,5s) isomer (0.17g, 14%), m.p. 202-203°C. 

The anion of the cyclopropyl sulfoxide 295 has been prepared with n-butyllithium in THF at — 20°C as shown by deuteration. The stereochemistry of the anion has not been investigated so far. 

A large number of cyclopropanes have been synthesized from cyclopropyl sulfones, cyclopropyl sulfoxides and cyclopropyl sulfides by taking advantage of the acidity of the cyclopropyl proton a to the C-S bond. Butyllithium is used almost exclusively as the base. The cyclopropyl anions obtained are capable of reacting with alkyl halides, aldehydes, enamines, epoxides, esters. 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

Cyclopropyl sulfoxides are readily oxidized to the corresponding sulfones. Thus, treatment of 4-tolyl 1, ci5-2,tra jf-3-triphenylcyclopropyl sulfoxide (1) with potassium permanganate in acetic acid gave 4-tolyl l,m-2,tram-3-triphenylcyclopropyl sulfone (2) in 50% yield. ... 

Methylation of t-butyl-l-dimethylphosphono-2-p-tolylsulfinyl cyclopropanecar-boxylic ester has been shown to occur with inversion of configuration. Reaction of cyclopropyl sulfoxide with Pr MgCl leads to 1,2-migration of the phosphoryl group (Scheme ( )... 

Diethyl N-cyclopropyl(6-chloro-5-trifluoromethyl-2-pyridinyl)amino-methylenemalonate (1701, R = Cl, R1 = Et) was obtained in the reaction of sodium salt of diethyl cyclopropylaminomethylenemalonate and 2,6-dichoro-3-trifluoromethylpyridine in dimethyl sulfoxide at 50°C for 4 hr in 86% yield (90JHC1527). When 1701 (R = Cl, R1 = Et) was reacted with ethoxycarbonylpiperazine in dimethyl sulfoxide at 100°C for 16 hr, then a 1 1 mixture of 2-pyridylaminomethylenemalonate (1701, R = 4-eth-oxycarbonylpiperazinyl, R1 = Et) and 2-(cyclopropylamino)-6-ch oro-5-trifluoromethylpiridine were obtained in 40% yield. However, the 6-phe-nylthio derivative (1701, R = SPh, R1 = Et) was prepared in high yield in the reaction of the 6-chloro derivative (1701, R = Cl, R1 = Et) and sodium phenylsulfide in dimethyl sulfoxide at ambient temperature for 2.5 hr. 

Chiral 2,2-disubstituted cyclobutanones have been obtained by asymmetric rearrangement of chiral sulfinyl- 177,178 and sulfanylcyclopropanes.179 Using readily available cyclopropyl 4-tolyl (/ )-sulfoxide (l),180 the requisite sulfinylcyclopropanes 3 and 3 were obtained by a sequence of lithiation, reaction with carboxylic acid esters and stereoselective addition of Grignard reagents to the ketones 2 thus formed.178 The corresponding sulfanylcyclopropanes 4 and 4 resulted from a sequence of protection, reduction and deprotection.179... 

Generally, chiral tricoordinate centers are configurationally stable when they are derived from second-row elements. This is exemplified by sulfonium salts, sulfoxides and phosphines. In higher rows, stability is documented for arsines and stibines. In contrast, tricoordinate derivatives of carbon, oxygen, and nitrogen (first-row atoms) experience fast inversion and are configurationally unstable they must therefore be viewed as conformationally chiral (see Fig. 3, Section 3.b). Oxonium salts show very fast inversion, as do carbanions. Exceptions such as the cyclopropyl anion are known. Carbon radicals and carbenium ions are usually close to planarity and tend to be achiral independently of their substituents [21-23]. 

Normal nucleophilic substitution occurred on treatment of 2-carbamoyl-3-chloropyrazine with alcoholic methylamine at 130° (423, 836) 2-chloro-3-(4 -morpholinocarbonyOpyrazine with morpholine at reflux in benzene (867) 2dimethyl sulfoxide at 65° (857) and cyclohexylamine in benzene at reflux (946) 3-chloro-2-methoxycarbonyl-5-phenylpyrazine with alcoholic methylamine at 140° (375) 2-carboxy-3-chloropyrazine with anhydrous ammonia at 100° for 5 hours (947) 2-carbamoyl-6-chloropyrazine with aqueous methylamine at reflux (940) 2-chloro-6-(4 -morpholinocarbonyl)pyrazine (and other amides) and 2-chloro-6-methoxycarbonylpyrazine with morpholine (and other amines) (870, 948, 949) and 2-chloro-6-methoxycarbonylpyrazine with liquid ammonia at 80° (870). 2-Chloro-3-methoxycarbonylpyrazine fused with guanidine carbonate gave 2-amino4-hydroxypteridine and its 7-methyl-, 7-phenyl, and 6,7-diphenyl analogues were prepared similarly (371,375). 

More investigations have been performed with cyclopropyl ketones. The isomerization of the cis-cyclopropyl ketone 209 to its trans isomer 210 was only achieved by means of the rather basic dimsyl sodium in dimethyl sulfoxide at 60°C . Similarly, esters of cyclopropane carboxylic acids have been isomerized ... 

Addition of the a,3-unsaturated anion (21) to the Michael acceptor (22), in which either alkylation or 1,4-addition is possible, affords only the Michael product. Internal alkylation of the interme ate ester enolates leads to cyclopropyl derivatives (equation 7). Terpenoid polyenes are prepared through conjugate addition of the lithiat protected cyanohydrins (23) to dienyl sulfoxide (24 equation 8). ... 

Dimethyl sulfoxide-derived reagent (c). Dimethyloxosulfonium methylide, (C H. i)2S=C H 2. This more stable reagent introduced by Corey reacts with monofunctional carbonyl compounds to give epoxides (oxiranes), but with a,/3-unsaturated ketones it gives cyclopropyl ketones. In one procedure a mixture of 0.1 mole each of powdered sodium hydride and trimethyloxosulfonium iodide (I) - is placed in a three-... 

Cyclopropyl thioacetals are conveniently prepared by treating 1,1-dichlorocyclopropanes with a thiol under basic conditions using methanol, ethanol or dimethyl sulfoxide as solvent. Almost all the thioacetals synthesized this way are l,l-bis(phenylsulfanyl)cyclopropanes. The reaction... 

Irradiation at 350 nm of 1,1-dibromocyclopropanes dissolved in liquid ammonia or dimethyl sulfoxide in the presence of sodium benzenesulfanate leads to l,l-bis(phenylsulfanyl)cyclo-propanes. The yields are in all cases below 50% which is due to both decomposition of the product on longer irradiation and formation of significant amounts of cyclopropyl phenyl sulfide. Most 1,1-dichlorocyclopropanes are unreactive, and no reaction occurs in the presence of oxygen, di- erf-butyl nitroxide and 1,3-dinitrobenzene, which supports the notion that the reaction is a radical process. The cleanest reaction took place during irradiation of 2,2-dichloro-1 -methylcyclopropanecarbonitrile, which gave no sulfide, little unreacted starting material, and 1-methyl-2,2-bis(phenylsulfanyl)cyclopropanecarbonitrile (4) in 47% yield. 

A number of cyclopropyl silyl ethers have been prepared by treating cyclopropanols with chloro-silanes. Most frequently the alcohol is reacted with chlorotrimethylsilane in the presence of a weak base such as triethylamine, or pyridine, but reactions without base present have also been performed. The yields are often good thus, l-(l-ethylidenehexyl)cyclopropanol reacted with chlorotrimethylsilane in diethyl ether and dimethyl sulfoxide containing triethylamine to give l-(l-ethylidenehexyl)-l-trimethylsiloxycyclopropane (1) in excellent yield. ... 

Efficient oxidation also results from treatment of cyclopropyl phenyl sulfide (7) with ( —)-camphorsulfonyloxaziridines 8. Due to the optical activity of the reagents, the product cyclopropyl phenyl sulfoxide 9 is optically active. The best results were obtained when (-)- , -dichlorocamphorsulfonyloxaziridine [( —)-8b] was used the sulfoxide was obtained in 90% yield with 92% ee of the 5 -isomer. Application of ( —)-camphorsulfonyloxaziridine ( —)-8a, on the other hand, lowered both the yield and the enantiomeric excess to 23%.Moderate optical purity was obtained when cyclopropyl phenyl sulfide was incubated with Mortierella isabellina, cyclopropyl phenyl sulfoxide was isolated in 58% yield with 66%ee of the (-1-)-sulfoxide, together with cyclopropyl phenyl sulfone (2% yield). Optically inactive cyclopropyl phenyl sulfoxide was obtained in 98% yield when the corresponding sulfide was treated with sodium metaperiodate. ... 

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