Cyclopropanones as intermediates

Photochemical ring contraction of various substrates, e.g. cyclobutane-1,3-diones and 1 -pyrazolin-4-ones - gives either isolable cyclopropanes or cyclopropanones as intermediates which are usually intercepted as adducts or which fragment to alkenes and carbon monoxide. The photoextrusion process most often leads to fragmentation products. 

A possible mechanism for the observed transformation includes the sequence outlined in Scheme 2.327 (i) propargyl (A) - allene (B) tautomerization, (ii) 8jt-cyclization (C), (iii) N-0 cleavage (diradical D), (iv) diradical recombination (cyclopropanone derivative E), and (v) one or two step cyclizations of the azadienyl cyclopropanone into azepinone F. The occurrence of cyclopropanones (type E), as intermediates, is supported by the formation, in some cases, of isoindoles (type I) (789) as minor products (Scheme 2.327) (139, 850, 851). 

There is considerable evidence that the rearrangement involves cyclopropanones and/or the 1,3-dipolar isomers of cyclopropanone as reaction intermediates.39... 

Cyclopropanones deserve special comment, not because of their practical importance (they have no commercial value at this time), but because of their novel behavior and reactivity. No unambiguous synthesis of cyclopropanones was known prior to 1965, and the older textbooks usually contained statements such as cyclopropanones apparently cannot exist. However, they had been postulated as intermediates in various reactions (see, for example, the Favorskii rearrangement, Section 17-2C and Exercise 17-15), but until recently had defied isolation and identification. The problem is that the three-ring ketone is remarkably reactive, especially towards nucleophiles. Because of the associated relief of angle strain, nucleophiles readily add to the carbonyl group without the aid of a catalyst and give good yields of adducts from which the cyclopropanone is not easily recovered ... 

The rearrangement of cyclopropanones, often obtained as intermediates from the base-catalyzed reaction of a-halo ketones, leading to carboxylic acids and derivatives. 

But is the same cyclopropanone an intermediate in the Favorskii reaction If the bromoketone is treated with methoxide in methanol, it gives the Favorskii product but, if it is treated with a much more hindered base, such as the potassium phenoxide shown, it gives the same cyclopropanone with the same stereochemistry. 

The chemistry of cyclopropylideneamines 1, the nitrogen analogs of cyclopropanones 2, was only elucidated during the 1980s. Many reports have proposed the participation of cyclopropylideneamines as intermediates in several reaction mechanisms. 

A conceivable mechanism for this reaction considers that malonate anion initially reacts as a base to give an equilibrium mixture of zwitterion 2 and cyclopropanone 3 intermediates, which have been suggested to be involved in the Favorskii rearrangement. ... 

A noteworthy example of an unexpected result in this area is the cyanation of l-chloro-3-phenyl-propan-2-one (15) with sodium or potassium cyanide in aqueous acetone which yielded the condensation product 16 in 55% yield.It is proposed that the reaction occurs via a Favorskii-type 1,3-dehydrochlorination, followed by trapping of the intermediate cyclopropanone 18 by cyanide to give cyanohydrin 19, which is not isolable. Instead, it adds across the intermediate cyclopropanone 18 to give adduct 20, which opens in the so-called normal way to afford the most stable carbanion 21, the benzylic carbanion. On protonation, the final cyclopropanecar-bonitrile 16 is formed and isolated as one stereoisomer, resulting from stereospecific addition of cyanide to the intermediate cyclopropanone. As expected, the isomeric 1-chloro-l-phenyl-propan-2-one (17) reacted in similar manner with aqueous cyanide to afford adduct 16, albeit in a lower yield. 

Favorski167 noted the formation of acid derivatives when strong bases act on a -halo ketones. The structure of the acid formed can be derived by postulating as intermediate a cyclopropanone derivative whose ring is opened by the base, thus ... 

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. ... 

The reaction has been subjected to extensive mechanistic study. There is strong evidence that the rearrangement involves the open 1,3-dipolar isomers of cyclopro-panone and/or cyclopropanones as reaction intermediates. ... 

We have investigated the reaction of NH phosphinous amides with diphenyl-cyclopropanone. The products were unequivocally identified as the corresponding p-phosphinyl carboxamides 27 resulting from the hydrolysis of a presumed heterocyclic intermediate (Scheme 28) These results await publication. 

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

When the two carbonyl substituents are identical, either the cyclopropanone or the dipolar equivalent is symmetric. As the a- and a -carbons are electronically similar (identical in symmetrical cases) in these intermediates, the structure of the ester product... 

Product distribution in the reaction of 4 with furan depends on the reaction conditions as well as on the oxy group of the acetal substrates 4a-c. The diverse products formed in the reaction of 4a-c with furan are rationalized by the reaction pathways illustrated in Scheme 13. All products arise from nucleophilic addition of furan to alkylideneallyl cation intermediate 5M (5S), which is generated by acid-mediated ring opening of cyclopropanone acetals 4a-c (Scheme 5). The [4 + 3] cycloadduct 23 is simply formed via 27, and the furanyl... 

The reaction of allenes with peracids and other oxygen transfer reagents such as dimethyldioxirane (DM DO) or hydrogen peroxide proceeds via allene oxide intermediates (Scheme 17.17). The allene oxide moiety is a versatile functionality. It encompasses the structural features of an epoxide, an olefin and an enol ether. These reactive intermediates may then isomerize to cyclopropanones, react with nucleophiles to give functionalized ketones or participate in a second epoxidation reaction to give spirodioxides, which can react further with a nucleophile to give hydroxy ketones. 

Semiempirical calculations have been used to study the mechanism of the ring opening of cyclopropanone and substituted analogues in a range of solvents of varying polarity. Transition states and oxyallyl intermediates have been characterized, as have the effects of solvents on their stability. The results are also compared with kinetic data in the literature. 

Treatment of pulegone dibromide with sodium hydroxide leads to a cyclopentane-carboxylic acid [216], Unidirectional opening of the cyclopropanone intermediate is caused by the bromine atom at the p-position which acts as a donor. 

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. 

In 2003, irradiation of isoxazolium anhydrobase in acetonitrile has been reported to give a novel (3-lactam system such as a 4,5-dihydrofuroazetidinone (yield 60%) [174], The mechanistic interpretation of this result involved a photochemical N-O bond cleavage, followed by the formation of a cyclopropanone intermediate (Scheme 75). 

Until quite recently, cyclopropanones were known only as transient intermediates, or in the form of derivatives such as the hydrate or hemi-acetal. x> During the past decade, however, through the work of the groups at Columbia 2> and Amsterdam 3> among others, methods have been developed for preparing a number of representatives of this class. Table 1 lists various cyclopropanones which have been isolated as well as several, more elusive examples which have been characterized in solution. 

In connection with the above discussion, formation of 3,3-disubsti-tuted 2 (3 H)-oxepinones (73) in the dye-sensitized photooxygenation of 6,6-disubstituted fulvenes is of special interest. 57>58> The reaction may be pictured in terms of an allene oxide intermediate which, as shown in Scheme 11, isomerizes to a cyclopropanone, followed by intramolecular rearrangement. 

Presumably, 1-acetoxycyclopropanol (88) is the intermediate in this reaction as well as that between the hydrate and ketene. 80> Although 88 has not been isolated in the above cases, it may be prepared from acetic acid and cyclopropanone and reacts with ketene to give 87. 5>15>... 

An extension of this reaction leading to a general synthesis of N-substituted (3-lactams involves the addition of a primary amine to a freshly prepared solution of cyclopropanone, conversion of the resulting carbinol amine to the N-chloro derivative, and then decomposition of this intermediate with silver ion in acetonitrile. 87a> The method permits one to prepare N-substituted (3-lactams of great variety (Table 14), including those constructed from amino acid esters. 87b The use of valine ethyl ester (123) as a nitrogen source leading to 124 is illustrated. 

Alkyl substituted cyclopropanols and cyclopropanone hemiacetals 115,116a) aiso undergo oxidative cleavage when exposed to air or peroxides the initial products are hydroperoxides such as 148. In the case of l-methoxy-2,2-dimethylcyclopropanol, the reaction can be followed by observing the emission peaks in the NMR spectrum, and these CIDNP effects have enabled identification of radical intermediates.1154) With di-f-butylperoxylate (TBPO), the isomeric radicals 143 and 144 are formed and these may undergo a diverse number of further reactions as indicated by the complex product mixture given in Table 20. 

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