Sulfide, 1 - cyclopropyl phenyl

The ambivalent aptitude of sulfur [19] to stabilize adjacent anionic as well as cationic centers is a remarkable fact that has shown to be a reliable feature for the assembly of four-membered ring scaffolds utilizing cyclopropyl phenyl sulfides [20]. Witulski and coworkers treated the sulfide 1-69 with TsOH in wet benzene (Scheme 1.19) [21]. However, in addition to the expected cyclobutanone derivative 1-70, the bicyclo[3.2.0]heptane 1-70 was also obtained as a single diastereoisomer, but in moderate yield. Much better yields of 1-71 were obtained using ketone 1-72... 

A more recent approach, which also profits from the synthetic versatility of stabilized thionium ions, has been elaborated by Berard and Piras [22]. These authors observed that the cyclobutane thionium ions 1-76 obtained from the cyclopropyl phenyl sulfides 1-75 by treatment with pTsOH under anhydrous conditions can be trapped by an adjacent electron-rich aromatic ring to give the chromane derivatives 1-77 in good to excellent yields (Scheme 1.20). As expected, 1-77 were obtained as single diastereoisomers with a ds-orientation of the methyl and the phenylthio group as a consequence of steric constraints. 

A 3-L, three-ncck, round-bottom flask, equipped with an internal thermometer, a N2 inlet, a mechanical stirrer, and a 1-L pressure-equalizing addition funnel, was charged with cyclopropyl phenyl sulfide (168 g, 1.12 mol) and anhyd THF (1200 mL). The solution was cooled to 0 °C in an ice bath. To the stirred solution... 

Method B To a solution of cyclopropyl phenyl sulfide (2.87 mL, 20.0 mmol) in anhyd TITF (100 mL) at 0 C under argon was added 1.31 M BuLi in hexane (15.3 mL, 20.0 mmol) and the resulting mixiure stirred... 

A variety of three-membered carbocycles including cyclopropylcarbonyl and -sulfonyl derivatives, cyclopropylcarbonitriles and -methanols, nitrocyclopropanes, cyclo-propanols and cyclopropylamines have been prepared via the 1,3-elimination of HX. Some representative cyclopropyl derivatives recently prepared by this method are shown in Scheme 116-18 and in equations 8-26. Conversion of chelated homoserine, 5,to chelated 2-amino-4-bromobutyrate and treatment with aqueous base directly affords chelated 1-aminocyclopropane-l-carboxylate (equation 8)19. The 1,3-elimination in 6 interestingly leads to the preferential formation of the cis isomer, from which 7, a key structural element of synthetic pyrethroid insecticides, is obtained (equation 9)20. A sulfur substituent can serve both as an activating group and as a leaving group in this type of reaction and, thus, 1,3-bis(phenylthio)propane affords cyclopropyl phenyl sulfide upon treatment with butyl-... 

The reagent cleaves epoxides regioselectively to give 1 -(/1-hydroxy)cyclopropyl phenyl sulfides, which are cleaved by HgCl2 to a,/ -enones (equation II).1... 

Preparation. The reagent can be prepared from phenyl 3-chloropropyl sulfide or from cyclopropyl phenyl sulfide. ... 

Several other applications of this method have been published. Reductive lithiation of l-(trimethyl-silyl)cyclopropyl phenyl sulfide gives a-lithio(trimethylsilyl)cyclopropane, which reacts with carbonyl... 

Haloalkyl phenyl sulfides produce cycloalkyl phenyl sulfides on treatment with base. The synthesis of cyclopropyl phenyl sulfides has attracted particular interest since these compounds can be metal-lated - - by Bu"Li in THF and the resulting 1-phenylthiocyclopropyllithium has been used for spiro-annelation of various cycloalkanones. - Thus, 3-chloro-l-phenylthiopropane leads to phenylthiocyclopropane on reaction with potassium amide in liquid ammonia (Scheme 7, entry a), but attempts to prepare 2-methylcyclopropyl phenyl sulfide from 3-chloro-l-phenylthiobutane by an analogous route failed in the cyclization step. Neither 3-mesyloxy- and 3-tosyloxy-l-phenylthiododecanes " nor 3-tosyloxy-l-phenylthiobutane produce cyclopropane derivatives either on reaction with LDA in THF (Scheme 7, entry b). Failure in these ring closure reactions has been attributed to inadequate car-... 

Cyclopropyl aldehydes, 120-121 Cyclopropyl ketones, 218 Cyclopropyl phenyl ketone, 112 Cyclopropyl phenyl sulfides, 231 Cyclosativene, 24... 

Lithiocyclopropyl phenyl sulfide, 5, 372-373 6, 319-320 7, 190. A new synthesis is outlined in equation (I). The method provides a general route to cyclopropyl phenyl sulfides.1... 

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. 

The cyclopropyl anion probably used the most, 1-lithio-l-phenylsulfanylcyclopropane, is obtained when cyclopropyl phenyl sulfide undergoes hydrogen abstraction when treated with butyllithium or another strong base. This anion has been treated with a very large number of aldehydes and ketones and afforded, often in very good yield, a large variety of 1-phenylsul-fanylcyclopropylmethanols (see Table number of cases the cyclopropyl-... 

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. 

The same general methodology applied to the preparation of alkenyl(silyl)cyclopropanes (vide supra) was previously developed for preparing alkenyl(sulfanyl)cyclopropanes. In this method, the lithium derivative of cyclopropyl phenyl sulfide (1) was used to alkylate a ketone and the resulting tertiary alcohol 2 was then dehydrated to give the product... 

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. ... 

Formation of sulfide with concurrent ester hydrolysis was achieved when various Cj cyclopropyl cephalosporin 5-oxide 2,2,2-trichloroethyl esters were treated with phosphorus trichloride followed by zinc under acidic conditions. Sulfoxide reduction also occurred on treatment of cyclopropyl phenyl sulfoxide with a mixture of benzenethiol and chlorotrimethylsilane in chloroform to give cyclopropyl phenyl sulfide in 76% yield and on reaction of various substituted cyclopropyl phenyl sulfoxides with diisobutylaluminum hydride. ... 

Alternatively, 1-phenylsulfanylcydopropyllithium (58), prepared by metalation of cyclopropyl phenyl sulfide (57) with butyllithium, has also been used successfully for the synthesis of cy-clobutanones. Addition to ketones, both saturated and unsaturated, leads to the desired 1,2-adducts 59 in high yield. Subsequent treatment of these cyclopropyl alcohols with either aqueous tetrafluoroboric acid at room temperature or anhydrous tin(IV) chloride in di-chloromethane afforded the corresponding cyclobutanones 60 in 65-88% yield. ... 

CYCLOBUTENES Cyclopropyl phenyl sulfide. Lithium aluminum hydride. 

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