Cyclopropanones cleavage

Nucleophilic addition of the base to the intermediate 2 leads to ring opening. With a symmetrically substituted cyclopropanone, cleavage of either Ca-CO bond leads to the same product. With unsymmetrical cyclopropanones, that bond is broken preferentially that leads to the more stable carbanion 5 ... 

Cyclopropanone cleavage with elimination 72 can also lead to ring contraction as in the synthesis of the trans acid 74 from natural pulegone13 70. Bromination gives the unstable dibromide 71 that is immediately treated with ethoxide to initiate the Favorskii rearrangement. The product is a mixture of cis and trans isomers of the ester 73 but hydrolysis under vigorous conditions (reflux in aqueous ethanol) epimerises the ester centre and gives exclusively the trans acid 74. 

This mechanism for cyclopropanone cleavage is supported by recent deuterium-incorporation, experiments [2gg]. The reaction in CH3OD/ D2O as solvent gave products with only one deuterium atom in the methyl group, consistent with the addition of D+ during the final step. 

The formation of a cyclopropanone derivative (originally determined by the isolation of degradation products from this unstable species) stimulated considerable interest in this reaction. Tetramethylcyclopropanone, however, cannot be isolated from the reaction mixture under normal photolysis conditions even with the use of an inert solvent. That it is indeed formed as an initial product of a-cleavage results from various trapping experiments in which chemical agents present in the reaction mixture were used to produce stable derivatives of the cyclopropanone [see equation (4.65)]. 

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). 

Cyclopropanones are also reactive toward cycloadditions of various types. Probably a dipolar species is first formed from reversible cleavage of cyclopropanone ring. 

As usual, the key to this problem is numbering correctly. The main question is whether the ester C in the product is C3 or C4. Because a ring contraction from 6- to 5-membered is likely to proceed by a Favorskii rearrangement, where the last step is cleavage of a cyclopropanone, it makes sense to label the... 

Horse radish peroxidase on the other hand, is a hemoprotein which is inhibited by alkylation of the porphyrin ring 48 by a -propionic acid radical resulting from the ring cleavage of the cyclopropanone hydrate 21, providing the car-boxylate 49,Eq. (17). 

Cyclopropanones are also reactive toward certain types of cycloadditions. Theoretical modeling indicates that a dipolar species resulting from reversible cleavage of the cyclopropanone ring is the reactive species.96 cis-Disubstitutcd cyclopropanes with bulky substituents exhibit NMR features that indicate a barrier of 10-13 kcal/mol for... 

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). 

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. 

In this case the cleavage of the cyclopropanone system is directed by the concerted loss of the second bromine. The cis/trans ratio appears to be determined by a subsequent epimerisation in which the thermodynamically more stable trans isomer predominates. Hydrolysis of the mixed isomers with aqueous alkali leads to the exclusive formation of frans-pulgenic acid, resulting from the rapid base catalysed equilibration of the cis/trans esters and the retarded rate of hydrolysis of the sterically hindered cis ester. 

Table 15. Cleavage reactions of cyclopropanones with base...

Cyclopropanone acetals require far more vigorous conditions (concentrated acid and heating) for ring cleavage compared to hemiacetals. As shown in Scheme 28, the reaction may proceed in two directions, one involving O-protonation (a) and the other C-protonation (b). In the case of 1,1-diethoxycyclopropane where both paths are competitive, refluxing hydrochloric acid yields both chloroacetone and ethyl propionate (Table 17).25)... 

A cyclopropanone thioacetal has also been observed to undergo Ci—C2 cleavage under the normal conditions for thioacetal solvolyses.110> Thus, the esters 135 a and 135 b are formed when the 1,3-dithiopropane ketal of 7,7-norcarane is reacted with mercuric chloride. In this case, HgCl+ acts as an electrophile and attacks the three-membered ring. However, under similar conditions, the cyclopropanone methyl thioketal 136 forms the mixed ketal 137. While the authors consider this result to represent an unusual example of a nucleophilic displacement at a cyclopropyl carbon atom 110), the reaction mechanism may involve the inter-... 

When the cyclopropanone ring is unsymmetrically substituted, two radicals are produced if C1—C2 and Ci—C3 cleavages are competitive. In the reaction of l-methoxy-2,2-dimethylcyclopropanol with cupric ion, product studies indicate that approximately twice as much primary radical (143) is produced as tertiary (144) (Table 19). Although these two radicals would be expected to condense with methyl (3-methylcrotonate (145), addition of 145 to the reaction mixture does not affect the nature of the products and the principal materials obtained, 146 and 147, (Table 19) probably arise by radical coupling.113)... 

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. 

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). 

Another mode of reaction exhibited by cyclopropanones involves the cleavage of the C(2)-C(3) bond under thermolysis to generate the oxyallyl species. This can usually be trapped as a cycloadduct with a diene such as furan (equation 18). 

In the case of unsymmetrically substituted cyclopropanones, one would expect two possibilities for the ring cleavage, reflecting the relative stabilities of the anions formed according to Scheme 14. While this accounts for the facts in most cases, there are examples where the product distribution does not parallel the expected order of carbanion stability. Thus, in the reaction of 2,2-di-t-butylcyclopropanone , the main product is not derived from the primary carbanion but rather from the tertiary carbanion, as shown in Scheme 15. Here, the propensity of the C(l)-C(2) bond to cleave appears to be enhanced by steric considerations involving the presence of two bulky t-butyl substituents at... 

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