Cyclobutanones reactions with diazomethane

Acetoxycyclopropan-l-ol is a storable source of cyclopropanone. Reaction with diazomethane yielded cyclobutanone (11) and methyl aeetate via a low equilibrium concentration of free cyclopropanone.128... 

Mono- and bis(trimethylsilyl)-substituted cyclopropanones 15 are stable enough to be isolated. Reaction with diazomethane,131 trimethylsilyldiazomethane131 and diazoacetic acid es-ters 130 131 yielded mono-, bis- and tris(trimethylsilyl)-subslitutcd cyclobutanones 16 and 17. In all cases, the regio- and stereochemistry arc in accord with the general rules given. 

Dichloroketene Addition (Enol Ether to [i-Alkoxy-a-dichlorocyclobutanone). Of six different chiral auxiliaries screened for their ability to control stereochemistry in the reaction of dichloroketene with derived civ-propenyl enol ethers, the 10-diisopropylsulfonamidoisobomeol auxiliary was the best. Thus, following ring expansion of the initially formed cyclobutanone (4) with Diazomethane-Chmmium(II) Perchlorate, a-chloro-y-methylcyclopentenone was isolated in 60% yield and 80% ee [C(a)- ( face attack of the ketene] (eq 3). The auxiliary was also recovered in unspecified yield. 

Cyclobutanones may be prepared without isolating the intermediate cyclopropanone by adding the ketene to excess diazoalkane (-78°C, 30 min) . The intermediacy of cyclopropanones in this process has been shown by C-labeling studies and by comparison of the product distributions in the diazoalkane-ketene with the corresponding diazoalkane-cyclopropanone reactions. When the cyclopropanone precursor is un-symmetrically substituted, the reaction with diazomethane leads to a mixture of cyclobutanones . 

For monocyclic and many fused bicyclic ketones the general order of reactivity of3>4>6>7 5 has been observed in the reaction with diazomethane and derivatives. Cyclopropanones react smoothly with diazomethane and diazoethane in the absence of catalysts to form cyclobutanones (equations 1 and 2). ... 

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. ... 

The best large-scale preparation of cyclobutanone is the reaction of diazomethane with ketene.2 It requires a ketene generator and implies handling of large quantities of the potentially hazardous diazo compound. A more frequently used method for the preparation of cyclobutanone starts from pentaerythritol, the final step being the oxidative degradation of methylenecyclobutane,3,4 which can also be prepared from other precursors.5 A general survey of all methods used to obtain cyclobutanone has been published.6,7... 

Although this method is commonly used for preparation of the parent cyclobutanone (ketene,/ diazomethane see Houben-Weyl, Yol. 4/4, pp406), the reaction of substituted ketenes with diazomethane gives mixtures of 2- and 3-substituted cyclobutanones with the 3-substituted derivative being formed preferentially. 

Cyclobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,5 (3) ozonolysis of methylenecyclobutane, (4) epoxidalion of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(cu-chloropropyl)-l,3-dithiane.8... 

The diminished reactivity of cyclopentanones toward diazomethane, while an asset in the ring expansion of cyclobutanones, has also proven to be a disadvantage. Some examples in the older literature demonstrate the problem of further reaction to higher homologs. The successful expansion reactions with... 

It is well known that cyclobutanones can be transformed to cyclopentane derivatives directly with diazomethane or indirectly via the cyanohydrins218> 228), or with tris(phe-nylthio)methyllithium 219,220), but in many cases the reactions are not regioselective and lead to different regioisomers. Cyclobutyl ketones lead to substituted cyclopentanones in highly acidic media 226 and the synthesis of cyclopentanones from methylene-cyclobutanes requires a palladium catalyst 227). 

The utility of cyclopropanones as synthetic intermediates has hitherto been limited by their low accessibility. It has now been shown that a very convenient precursor of cyclopropanone is 1-acetoxycyclopropanol, the acetate group being readily replaced by various nucleophiles (e.g. CN, N3, NRj, OR, SR) via a low equilibrium concentration of the ketone. The existence of this equilibrium was demonstrated by treatment with diazomethane, giving cyclobutanone and methyl acetate. Similarly, the OH group of 1-dimethylaminocyclopropanol is readily replaced by all common nucleophiles via an S l reaction with (487) as intermediate. ... 

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... 

This method for the preparation of cyclobutanone via oxaspiropentane is an adaptation of that described by Salaiin and Conia. The previously known large-scale preparations of cyclobutanone consist of the reaction of the hazardous diazomethane with ketene, the oxidative degradation or the ozonization in presence of pjrridine of methylenecyclobutane prepared from pentaerythritol, or the recently reported dithiane method of Corey and Seebach, which has the disadvantage of producing an aqueous solution of the highly water-soluble cyclobutanone. A procedure involving the solvolytic cyclization of 3-butyn-l-yl trifluoro-methanesulfonate is described in Org. Syn., 54, 84 (1974). 

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