Ketones cyclopropanone

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 ... 

A THF or ethereal solution of selenoacetals derived from aldehydes must be added to n-BuLi or s-BuLi in hexane to avoid side reactions, i. e. their metalation is achieved not by the butyllithium but by the selanylalkyllithium produced in situ [11] (Scheme 10). Moreover, it was observed that selenoacetals formed from aromatic aldehydes and ketones, cyclopropanones are more reactive than those derived from aliphatic carbonyl compounds [11]. The second factor governing the reaction is the steric hindrance around the reactive site. Selenoacetals derived from aldehydes react in a few minutes but those derived from ketones... 

The currently accepted mechanism for the Favorskii rearrangement of dihalo ketones involves a cyclopropanone intermediate formed by loss of HX. This is followed by attack of alkoxide synchronous with cyclopropanone fragmentation and departure of halide ion to form the unsaturated ester... 

In the initial step " the a-halo ketone 1 is deprotonated by the base at the a -carbon to give the carbanion 4, which then undergoes a ring-closure reaction by an intramolecular substitution to give the cyclopropanone derivative 2. The halogen substituent functions as the leaving group ... 

Hemiacetals themselves are no more stable than the corresponding hydrates (16-1). As with hydrates, hemiacetals of cyclopropanones and of polychloro and polyfluoro aldehydes and ketones may be quite stable. 

The net structural change is the same for both mechanisms. The energy requirements of the cyclopropanone and semibenzilic mechanism may be fairly closely balanced.87 Cases of operation of the semibenzilic mechanism have been reported even for compounds having a hydrogen available for enolization.88 Among the evidence that the cyclopropanone mechanism operates is the demonstration that a symmetrical intermediate is involved. The isomeric chloro ketones 12 and 13, for example, lead to the same ester. 

It has been found that the bromo ketones 10-7a-c can rearrange by either the cyclopropanone or the semibenzilic mechanism, depending on the size of the ring and the reaction conditions. Suggest two experiments that would permit you to distinguish between the two mechanisms under a given set of circumstances. 

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. 

The mechanism of the novel transformation of a-nitro- to a-hydroxy-ketones has been probed. The reaction, which proceeds under basic aqueous conditions, requires that the Q -nitro substrate be CH-acidic in the a -position, and that it be readily depro-tonated under the conditions employed. NO2 -OH exchange occurs with retention of configuration, with the hydroxyl oxygen being predominantly derived from the solvent. A mechanism involving neighbouring-group participation, via a Favorskii-like cyclopropanone intermediate, is proposed. 

A double 5n2 reaction, which proceeds via a Favorskii-like cyclopropanone intermediate, has been proposed to account for the novel stereoretentive replacement of NO2 by OH on reaction of a-nitro ketones (which must bear an acidic hydrogen at the O -position) with aqueous base. ... 

The rearrangements of 3-methylbut-l-ene oxides" and l,2-epoxybut-3-ene on lithium phosphate have been studied, and a detailed theoretical study of the rearrangement of allene oxide (342) to cyclopropanone (344), which shows that the transformation proceeds via an intermediate oxyallyl (343), has been presented. It has been shown that aldehydes, ketones, and cyclic ethers are all produced... 

In order to activate the 21 position to halogenation, it is hrst converted to an oxalate. Condensation of the triketone with ethyl oxalate in the presence of alkoxide proceeds preferentially at the 21 position to give (12-2) due to the well-known enhanced reactivity of methyl ketones. Reaction of the crude sodium enolate with bromine leads to the dibromide (12-3), the oxalate moiety being cleaved under the reaction conditions. The Favorskii rearrangement is then used to, in effect, oxidize the 17 position so as to provide a site for the future hydroxyl group. Thus, treatment of (12-3) with an excess of sodium methoxide hrst provides an anion at the 17 position (12-4). This then cyclizes to the transient cyclopropanone (12-5)... 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

Alternatively, the reaction of cyclopropylethynylmagnesium bromide with cyclo-propanone hemiacetal gives l-(cyclopropylethynyl)cyclopropanol (equation 152)232. The reaction of cyclopropanone acetal with other alkynyl Grignard reagents serves as a general route to alkynylcyclopropanols. Similarly, alkynyllithium derivatives of vitamin D were coupled with cyclopropane carbonyl isoxazolidine to give the corresponding alkynyl-cyclopropyl ketones (equation 153). 

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. 

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 ... 

When seemingly simple organic structures defy isolation, this usually stimulates many theoretical and experimental studies in an effort to rationalize anomalous behavior. In the case of cyclopropanone, the possibility was considered that the molecule might preferably exist as an open-chain dipolar structure rather than as the cyclic ketone ... 

Although the spectral properties of cyclopropanones and the easy formation of hydrates and hemiketals are inconsistent with the dipolar form, some reactions of cyclopropanones do indicate that the ring carbons are much more electrophilic than in other cyclic or acyclic ketones. For example, nucleophilic ring opening often occurs easily ... 

How would you expect the proton nmr spectrum of cyclopropanone in the cyclic ketone and dipolar ion structures (Section 17-11) to differ Show your reasoning. 

It should be noted that in this case either of the carbonyl-carbon bonds in the symmetrical intermediate cyclopropanone system could be cleaved. With unsymmetrically substituted cyclic ketones (or indeed open chain ketones), the direction of cleavage is that which would lead to the more stable carbanion. 

A significant step in studying the chemistry of cyclopropanones has resulted from the discovery that many labile carbonyl derivatives such as hemiacetals and carbinol amines are useful precursors of the parent ketone. 4-6> Such derivatives may be isolated, purified and used as cyclopropanone substitutes or, alternatively, may be generated in solution and used as in situ precursors. As a result of these advances, exploration of cyclopropanone chemistry has recently been accelerated. The aim of this article is to review some of this chemistry, noting areas where there may be potential applications in synthesis. 

In reviewing the methods available for preparing cyclopropanones (Section 2), it becomes clear that a reliable, general method for the preparation of three-membered ketones has still to be devised. For example, the key combination of X and Y substituents and conditions needed to effect a conversion such as shown in Scheme 1 has not yet been discovered. 

A versatile synthesis of cyclopropanones and closely related derivatives is provided by the diazoalkane-ketene reaction as shown in Scheme 2. Using this method, the parent ketone 2>3> and alkyl-substituted cyclopropanones 1()) have been prepared in yields of 60—90% based upon the concentration of diazoalkaneb) (Table 2). The reaction is rapid at Dry Ice-acetone temperatures and is accompanied by evolution of nitrogen. Although most cyclopropanones are not isolable, dilute solutions of 3 (0.5—0.8 M) may be stored at — 78 °C for several days or at room temperature in the presence of suitable stabilizing agents.15) The hydrate and hemiketal derivatives are readily prepared by the addition of water or alcohols to the solutions of. .2>8>5)... 

As shown in Table 2, the application of this method to the synthesis of aryl-substituted cyclopropanones 16> and cyclopropanone acetals 17>18> has been moderately successful, although products other than the expected ketones may be obtained. For example, the oxadiazoline 4 and not tetraphenylcyclopropanone is formed when diphenylketene is allowed to react with diphenyldiazomethane.19>... 

In other special cases, cyclopropanones have been prepared by photochemical rearrangements. For example, 9,9 -dianthracyl ketone (27) 32> and carbinol (28) 33> undergo ring closure to their respective... 

Cyclization reactions by 1,3-dehalogenation or dehydrohalogenation d> have provided additional routes to cyclopropanones. The application of the former reaction to the formation of 3-ring ketones was suggested by the isolation of the cycloadduct 37 from the reaction of a, -dibromo-benzyl ketone with sodium iodide in the presence of the trapping agent furan.39> More recently, Giusti n> has synthesized several cyclopropanone... 

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