Cyclopropanones cyclobutanones

The most common reaction involving this type of cycloaddition is the reaction of ketenes with diazoalkanes (Houben-Weyl, Vol. 4/4, pp 406-408) which proceed via cyclopropanone intermediates. This type of reaction finds limited use due to nonregioselective formation of substituted cyclobutanones as mixtures. 

Proof that the intermediate cyclopropanones are involved in these reactions was shown by spectroscopic observation, isolation and trapping with various dipolarophiles.1 3 Yields of the double ring expansion products are quite good ranging up to 90% for the parent cyclobutanone,1 but the separation of the regioisomeric mixture can be tedious. 

Using diazomethane as the limiting reagent, silyl- and germyl-substituted ketenes5-7 in certain cases gave cyclopropanones which were isolated as stable compounds.5,6 Transformations of trimethylsilylketene and triethylgermylkelene to the 2- and 3-substituted cyclobutanones was accomplished in 90 and 82% yield, respectively. Mild reaction conditions (— 78 °C) in diethyl ether solutions were employed. 

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... 

In situ ring enlargement of intermediate cyclopropanones to silyl- and germyl-substituted cyclobutanones was achieved by treatment of silyl- and germyl-substituted ketenes 12 with an excess of diazomethane.129,130... 

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. 

Thus the hemiketal from cyclopropanone will have 109.5° — 60° = 49.5°, and that from cyclobutanone 109.5° — 90° = 19.5° of strain at Cl. This change in the angle strain means that a sizable enhancement of both the reactivity and equilibrium constant for addition is expected. In practice, the strain elfect is so large that cyclopropanone reacts rapidly with methanol to give a stable hemiketal from which the ketone cannot be recovered. Cyclobutanone is less reactive than cyclopropanone but more reactive than cyclohexanone or cyclopentanone. 

Butanedioic and pentanedioic acids take a different course. Rather than form the strained cyclic ketones, cyclopropanone and cyclobutanone, both acids form cyclic anhydrides that have five- and six-membered rings, respectively. 1,2-Benzenedicarboxylic (phthalic) and cis-, 4-butenedicar-boxylic (maleic) acids behave similarly ... 

The high-frequency shifts in the CO and CH stretching vibrations of cyclopropanones are related to ring strain and occur to a lesser extent in cyclobutanone. Although normal coordinate analysis has been employed in predicting these shifts, the theoretical models do not appear to be completely reliable.6 ) An important factor causing the above shifts... 

Cyclobutanones may be prepared in a one-step procedure, i.e., without isolating the intermediate cyclopropanone, simply by adding the ketene to excess diazoalkane. 97>98) That cyclopropanones are intermediates has been established by carbon-14 labeling studies "> and... 

It appears that this route to cyclobutanones is applicable only to the most stable as well as the most favorably substituted cyclopropanones. 

The three-membered ring is, of course, flat. The others are not. Even the four-membered ring is slightly puckered, the five- and especially the six-membered rings more so, This is all discussed in Chapter IB, But you have already met the concept of ring strain in Chapter 6, where we used it to explain why cyclopropanones and cyclobutanones are readily hydrated. 

Most importantly, additions of electrophiles to vinylcyclopropanes can lead to cyclobutanones if a suitably located donor substituent is present. It was Wasserman and coworkers who showed that vinylcyclopropanols—obtained from cyclopropanone hemiacetals and vinylmagnesium bromide—can be expanded to functionalized cyclobutanones (equation 147). ... 

A recent example of the preparation of a silylated and germylated cyclopropanone has been provided by Russian workers who added diazomethane in ether or methylene chloride at —130 °C to an equimolar amount of trimethylsilyl and trimethylgermylketene. The authors were able to obtain PMR spectra of the parent ketones which show an ABC system of cyclopropane ring protons at 0.8-1.8 ppm. These products react with methanol to form hemiketals and undergo ring expansion with excess diazomethane to form the corresponding cyclobutanone derivatives. 

As noted above, reactions of cyclopropanones with nucleophiles may yield intermediates such as vinyl cyclopropanols which are readily converted to cyclobutanones through carbinyl cations . In like manner, generation of electron-deficient nitrogen species may lead to the formation of ) -lactams by related ring enlargement Hydrazoic acid, amines and hydroxylamine derivatives have all been used in this context as shown in Scheme 12. These reactions are summarized in the examples outlined below. 

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). ... 

Cyclopropanones and cyclobutanones are very reactive, rather like epoxides, because, while the 60° or 90° angle in the ring is nowhere near the tetrahedral angle (108°), it is nearer 108° than the 120° preferred by the sp C of the C=0 group. Conversely, the small ring ketones are resistant to enolization, because that would place two sp carbon atoms in the ring. 

Vinyl cyclopropanols have been prepared by the addition of alkenyl Grignard reagents to a variety of cyclopropanone equivalents. Upon treatment with acid, the vinyl cyclopropanols rearrange to a-substituted cyclobutanones. Alternatively, a variety of a-heteroatora-substituted cyclopropyllithiura reagents have been developed. These react with aldehydes and ketones to afford cyclopropylcarbinols which also rearrange to cyclobutanones under acid catalysis.Lastly, vinyl cyclopropanols and cyclopropylcarbinols have been prepared by the cyclopropanation of enol silyl... 

Cyclobutyl compounds were found S7) to have reactivities closely related to the ones already disclosed for open chain and other cyclic derivatives 7 8,U). Moreover, in several instances, compounds possessing a cyclobutane ring have been prepared from a-selenoalkyllithiums and cyclobutanones (Compare Scheme 8B to 8 A) using the strategy already presented. This is not, however, the case of cyclopropane analogs due to the unavailability of cyclopropanones. 

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