Cyclopropanones intermediates

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... 

The cyclopropanone intermediate (81) undergoes subsequent addition of eOH, followed by ring-opening to yield the more stable of the two possible carbanions (83, benzyl > primary), followed by proton exchange to yield the rearranged carboxylate anion end-product (84). 

Ethyl phenyl cyclopropenone (14) on reduction with NaBH4 gave rise to prod ucts 289-291, which can be ascribed to a common cyclopropanone intermediate 288 ring-opened by further reduction or attack of solvent209 ... 

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. ... 

Benzenetetracarboxylic dianhydride derivatives undergo photolysis in a nitrogen matrix at 13 K to produce benzdiynes by a stepwise process which is dependent on the ring substituents <2002JA4512>. Upon irradiation at 308 nm, the dianhydrides are initially converted into cyclopropanone intermediate 85 by loss of carbon dioxide and subsequently decompose by loss of carbon monoxide to produce the benzyne (Scheme 5). 

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). 

Similarly, cyclopropanones have not been found among the products from the reaction of ethyl diazoacetate with dimethylketene or diphenylketene although cyclopropanone intermediates may be involved (see Section 4.1.5).20) Attempts to prepare the cyclic thioketal 5C) by the addition of diazomethane to the trithiane 6 were also unsuccessful.21)... 

The Favorski rearrangement normally goes with inversion at the terminus, as in 86 (semi-ezo-S) rather than 87 (semi-17). Reusch and Mattison (1967) have verified this for the pulegone oxides of which only one of the optically active forms is given in (181). It is of interest that the cyclopropanone intermediate opens abnormally, that is with retention. These authors note that their conditions are similar to those for electrophilic substitution with retention, namely frontside proton transfer from a polar aggregate (Cram, 1965). 

Eberbach and co-workers have reported [01EJO3313] a fascinating approach to benzazepinones 46 from the nitrone precursors 45. Treatment of 45 with base under unusually mild basic conditions gave 46 in generally high yields e.g. 46, R1 = R3 = H, R2 = Ph 84%). The overall transformation is the result of a complex series of steps proposed to include allene formation, 1,7-dipolar cyclisation and a series of bond cleavage and formation steps (via a cyclopropanone intermediate). 

Phenylethynylcopper and phenacyl bromide afford intractable tars upon long reflux in DMF. However, at higher temperatures ( 240°C) a-haloketones can be converted in one step to furan derivatives [Eqs. (68a), (68b)] uncyclized acetylenic ketones are not isolated. The cycliza-tion is catalyzed by copper(I) through the copper-coordinated enol 128). Reaction of a,a -dibromoketones with an excess of a diorganocuprate is a new method for the a-alkylation of a ketone 231a). Only the monoalkyl derivative is isolated. The evidence points to the formation of a cyclopropanone intermediate which reacts with more of the cuprate to give an a-alkylated metal enolate. 

The bicyclic product 59 proved not to be derived from diazo ketone 58. It may arise from the reaction of diazenyl ketene intermediate 53 with diazomethane via the postulated 2-[2-methyl-2-(phenyldiazenyl)propyl] cyclopropanone intermediate 60 and its subsequent isomerization to the bicyclic product 59 (Scheme 14). The formation of the diazenyl ketene intermediate 53 has been made plausible by carrying out the reaction in the presence of an excess of isobutyl alcohol to afford isobutyl 3-methyl-3-[(E)-phenyldiazenyl]butanoate (61) in a competing addition. 

The generally accepted mechanism for the Favorskii rearrangement involves the formation of reactive cyclopropanone intermediate C. Base abstracts the a-hydrogen from A to give the carbanion B, which undergoes intramolecular Sn2 displacement of the halide ion. The resulting cyclopropanone intermediate C is opened under the reaction conditions to give the more stable carbanion D, which takes proton from solvent to furnish the final product, an ester E (Scheme 2.25). 

In the symmetrical cyclopropanone intermediate, the two a-carbons are equivalent and ring opening via route a or route b gives the same carbanion. However, unsymmetrical cyclopropanone ring opens in such a way so that the more stable carbanion of the two possible carbanions is formed. 

These mechanisms were finally discounted by Loftfield [3047, who used the isotopically labelled compound 15) and showed that only half of the label appeared at the carboxyl-bearing carbon in the product. A mechanism involving the reactive cyclopropanone intermediate (16) accounts for the isotopic distribution, and has gained general acceptance... 

Reduction of 308 with sodium borohydride gives 24% tetraphenylethylene with lithium borohydride, 75% of 2,2-diphenylethanol and 16% of 2,2-diphenylethyl disulfide with di-isobutylaluminum hydride, 39% l,l,3,3-tetraphenyl-2-propanone and 30% of benzophenone. Lithium aluminum hydride gives four products that may be formed by way of cyclopropanone intermediates. ... 

The catalytic hydrogenation of various cyclopropenones gives acyclic ketones 318 via the corresponding cyclopropanone intermediate 317 3 - 2,444,445 contrast, Pd/C promoted reaction of di-n-propylcyclopropenone delivers the a,j5-unsaturated aldehyde... 

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. 

Enolization occurs on the side of the ketone away from the bromine atom and the enolate cyclizes as before but the cyclopropanone intermediate is symmetrical so that the product is the same whichever C-C bond breaks after nucleophilic attack by the methoxide ion. 

Favorskii rearrangement Skeletal rearrangement of a-halo ketones via a cyclopropanone intermediate to give carboxylic acids or carboxylic acid derivatives. 164... 

Numerous more recent experiments (reviewed in ref. 12) have confirmed the general accuracy of the mechanism shown in Scheme 4, and the actual intermediate involved depends upon the relative stabilities of the zwitterions/oxyallyl cations and the corresponding cyclopropanones. These will be affected by the choice of solvent and structural features of the starting ketone, such as the degree of substitution and ring strain (in cyclic halo ketones). A recent example in which an oxyallyl intermediate and a cyclopropanone intermediate were both intercepted is shown in Scheme 8. ... 

When the Favorskii rearrangement is carried out on a substrate which contains an internal nucleophile, this can attack the cyclopropanone intermediate to yield cyclic products. The reaction shown in Scheme 13 provides a route to polysubstituted "y-butyrolactones by this kind of mechanism. 

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