Cyclopropanone equivalents reactions

Cyclopropanone equivalent. Unlike cyclopropanone, which is difficult to isolate, 1 is stable, easily obtained from 3-chloropropionic acid (Aldrich), and is a useful substitute for the ketone. Thus reaction of the silyl ether 2 with RMgBr provides adducts in which the OH group of 1 is replaced by R. The carbinol 1 is also a useful precursor to pyrroles, pyrrolines, and pyrrolizidines (equation I). 

In this chapter, we will review methods for preparing cyclopropanones, their physical and spectroscopic properties, and the nature of their reactions with nucleophiles, electrophiles and in cycloaddition processes. Another part of the chapter will deal with cyclopropanone equivalents, 1,1-disubstituted systems which under certain conditions may provide carbonyl-related derivatives of the parent ketones. We will also discuss the role of cyclopropanones in biological phenomena and cite specific examples of the use of cyclopropanone intermediates as key units in the synthesis of natural products. 

The most recent source of these iminium ion precursors is the amide derived from 3-chloropropionyl chloride. Using the procedure reported by Ruhlmann for the preparation of 1-methoxy-l-trimethylsilyloxycyclopropane, Wasserman and Dion " converted the piperidide (58) to the 1-piperidino-l-trimethylsilyloxycyclopropane (59) by treatment with sodium metal in dry ether at 0°C. This reaction, which takes place smoothly and in high yield, serves as a short, inexpensive way to form the stable cyclopropanone equivalent. Further reaction of the silyl derivative (59) with tetrabutylam-monium fluoride in THF yields the corresponding carbinol amine (60). 

Displacement reactions on 1,1-disubstituted cyclopropanes have been used to prepare other cyclopropanone equivalents. The most readily available 1,1-disubstituted cyclopropanes are geminal dihalo derivatives prepared by the addition of dihalocarbenes to olefins. Unfortunately, these materials do not undergo direct displacement easily and therefore do not provide a general route to other cyclopropanone derivatives. Solvolysis usually leads to ring-opened products, although dibromocyclopropanes with a barrier to... 

Gem-dibromocyclopropanes can be converted into synthetically useful cyclopropanone equivalents by a process consisting of lithium-halogen exchange followed by reaction of lithiocyclopropane (113) with dimethyl disulfide (Scheme 43) . The resulting bromo-methylthio derivative (114) undergoes a variety of substitution reactions. Methanolysis gives S,0-dimethylketal (115) which can be converted into l,l bis(methyl-thio)cyclopropane (116) with methyl mercaptan in trifluoroacetic acid. Reaction of 114 with other nucleophiles provides the derivatives shown in Scheme 44 . The sulfur-... 

As discussed in an earlier section, displacement reactions on appropriately 1,1-disubstituted cyclopropanes may give rise to new cyclopropanone equivalents (see Schemes 43, 44). These reactions occur by S 1 processes involving carbenium ions of structure 136. In addition to being susceptible to ring-opening (Scheme 18) and trapping... 

Conversion of -chloro amide 8 by sodium metal in diethyl ether in the presence of chlorotrimethylsilane at 0 C smoothly afforded l-[l-(trimethylsiloxy)cyclopropyl]piperidine (5) in high yield. Reaction of this silyl derivative with tetrabutylammonium fluoride in tetrahydro-furan yielded the corresponding hydroxyamine 9. These preparations of 5 and 9 serve as short, inexpensive ways of forming cyclopropanone equivalents. 

There is evidence that the rearrangement involves cyclopropanones or their open 1,3-dipolar equivalents as reaction intermediates.86... 

Treatment of cyclopropane-1,1-diol with dimethylamine in the presence of molecular sieves gave aminal 2 (R =R = Me) directly.A more carefully executed study on the reaction of cyclopropanone with dimethylamine (4 molar equivalents) revealed that the reaction gave 26% of the adduct 3 and 28% of the dicyclopropyl ether 4. However, inverse addition of cyclopropanone to a solution of dimethylamine in dichloromethane at — 50 °C afforded the monoadduct 3 in 67% yield. 

Cyclopropanones react with Grignard reagents to give 1-substituted cyclopropanols. In practice, the reaction is executed with 1-ethoxycyclopropanol (i) 3.25,75,9o-93 i acetoxy-l-ethoxycyclopropane (3). In each case, two molar equivalents of the Grignard reagent are required to generate the cyclopropanol 2. 

Reaction of cyclopropanone ethyl hemiacetal with methylmagnesium bromide and two equivalents of cyclohexanone lithium enolate provides a very interesting and highly stereospecific synthesis of tricyclic cycloheptanones a serendipitous reaction... 

Reaction with aldehydes. This cyclopropanone ketal in the presence of TiClt behaves as the equivalent of the homoenolate anion of ethyl propanoate, O... 

Reaction with Diazomethane to Form Silylated Cyclopropanes and Cyclohutanones. The reaction of (1) and diazomethane results in a mixture of products. Treatment of equimolar amounts of (1) with diazomethane at — 130°C leads to (trimethylsilyl)cyclopropanone in moderate yield (eq 12). The product obtained can then react with a second equivalent of diazomethane upon warming to — 78°C, resulting in ring expansion to a mixture of 2- and 3-(trimethylsilyl)cyclobutanones. Alternatively, these isomeric products may be obtained directly with 2 equiv of diazomethane. Treatment of the isomeric (trimethylsilyl)cyclobutanone mixture with methanol makes it possible to obtain pure 3-substituted isomer in 84% yield. This 3-(trimethylsilyl)cyclobutanone derivative can also be formed by a more elaborate route via the regioselective [2 + 2] addition of dichloroketene to trimethylsilylacetylene followed by hydrogenation and reductive removal of the two chlorine atoms. trimethylsilyidiazomethane has also been reported to react with (1) to form bis-silyl substituted cyclopropanones. ... 

In the reaction of ketene with diazomethane, cyclopropanone is initially formed, which reacts with another equivalent of diazomethane to give cyclobutanone ". Diazoketones react with ketenes by addition to the diazo compound. The cycloadduct eliminates nitrogen to produce butenolides. However, the ketocarbene 370, generated from... 

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