Cyclopropanes Substituted with Carbonyl Groups

The first report on what turned out to be a reduction of a carbonyl substituted cyclopropane was published in 1949 41. Reaction of methyl cyclopropyl ketone 33 with sodium in liquid ammonia in the presence of ammonium sulfate yielded instead of the expected methyl cyclopropylcarbinol 34 a mixture of 2-pentanone 35 and 2-pentanol 36. 

From an investigation of several conjugated cyclopropyl ketones, as e.g. 37, Norin discovered 42) that the steric course of the reaction depends on the configuration of the cyclopropyl ketone in such a way that the cyclopropyl bond which is cleaved is the one possessing maximum overlap of the Walsh orbitals with the k-orbitals of the carbonyl group. 37 thus leads to 38. 

By means of the cyclopropyl ketones 39, cis-40 and trcms-41, in which the two bonds of the cyclopropane ring, C-l-C-2 and C-l-C-3, are free to overlap with the carbonyl 7t-system, Dauben evaluated the importance of stereoelectronic versus steric factors43). 

The main products in the reaction mixtures of the 2,2-dimethylcyclopropyl ketone 39 and the cis-2-methylcyclopropyl ketone cis-40, respectively, result from C-l-C-2 bond breaking. In contrast, the frartj-2-methylcyclopropyl ketone trans-41 breaks the C-l-C-3 bond. This strongly suggests that steric factors control the direction of cleavage, presumably through asymmetric overlap of the carbonyl 7r-system with one of the cyclopropane bonds 43). In the absence of these steric effects, as in trans-41, the bond that cleaves is the one to give the more thermodynamically stable (= less substituted) carbanion intermediate. 

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In any chain reaction, apart from initiation steps, the termination steps are also important. In metathesis there are many possibilities for termination reactions. Besides the reverse of the initiation step, the reaction between two carbene species is also a possibility (eq. (17)). The observation that, when using the Me4SnAVCl6 system, as well as methane traces of ethylene are also observed [26] is in agreement with this reaction. Further reactions which lead to loss of catalytic activity are (1) the destruction of the metallacyclobutane intermediate resulting in the formation of cyclopropanes or alkenes, and (2) the reaction of the metallacycle or metal carbene with impurities in the system or with the functional group in the case of a functionally substituted alkene (e. g., Wittig-type reactions of the metal carbene with carbonyl groups). 

With an acceptor-substituted alkene moiety tethered to the molecule, the intermediate silyl enol ether may undergo an intramolecular [2-I-2] cycloaddition.The silyl-assisted addition of hydrogen halides to cyclopropanes is not restricted to ketones with carbonyl groups as activating function or iodide as nucleophile. Esters and other acid derivatives underwent similar reactions when treated with iodotrimethylsilane alone or in the presence of an additional catalyst such as mercury(II) or zinc(II) chloride.Subsequent treatment of the y-iodo ester with potassium carbonate in tetrahydrofuran gave the respective y-butyrolactones in good yield. 

This novel reaction, which in a formal sense involves an ethylene dianion (CH2 —CH22 ) equivalent, can also be conducted with substoichiometric amounts of titanium(IV) isopropoxide (0.05--0.1 equiv) at 20°C.148 149 Using this method several 1-substituted cyclopropanols 2 were prepared. It is likely that the cyclopropanation of the carbonyl group is brought about via an intermediate diisopropoxytitanacyclopropane. 

Salaiin, J. R. Y. Synthesis and Synthetic Applications of 1-Donor Substituted Cyclopropanes with Ethynvl, Vinyl and Carbonyl Groups, 144, 1-71 (1987). 

Some remarks concerning the scope of the cobalt chelate catalysts 207 seem appropriate. Terminal double bonds in conjugation with vinyl, aryl and alkoxy-carbonyl groups are cyclopropanated selectively. No such reaction occurs with alkyl-substituted and cyclic olefins, cyclic and sterically hindered acyclic 1,3-dienes, vinyl ethers, allenes and phenylacetylene95). The cyclopropanation of electron-poor alkenes such as acrylonitrile and ethyl acrylate (optical yield in the presence of 207a r 33%) with ethyl diazoacetate deserve notice, as these components usually... 

The [Rh(CO)2Cl]2-induced ring fission of substituted cyclopropanes 8a-b affords the rhodium complexes 9a-b via carbonylation [8]. The regioselectivity of carbonyl group insertion depends on the substituent. Reduction with NaBH4 leads to the corresponding alcohol. (Scheme 4)... 

Electron-withdrawing substituents generally increase diazo compounds stability toward decomposition. Dicarbonyl diazomethane, which bears two carbonyl groups flanking the diazomethane carbon, are more stable than diazo compounds with only one carbonyl substituent. In general, metal catalysed decomposition of dicarbonyl diazomethane requires higher temperature than does monocarbonyl substituted diazomethane. As indicated before, rhodium(II) carboxylates are the most active catalysts for diazo decomposition. With dicarbonyl diazomethane, the rhodium(II) carboxylate-promoted cyclopropanation process can also be carried out under ambient conditions to afford a high yield of products. 

Phenyl, vinyl or carbonyl substituted cyclopropanes are more easily hydrogenolyzed than are the alkyl substituted species. Such compounds are commonly cleaved over palladium catalysts at room temperature and atmospheric pressure. Hydrogenolyses run over platinum, rhodium or nickel catalysts frequently result in the saturation of the double bond, the benzene ring or the carbonyl group with the cyclopropane ring remaining intact or cleaved to only a slight extent. 20 As illustrated in Fig. 20.22 the bond broken in the... 

Substitution at the cyclopropane ring is also observed when diazocyclopropane reacts with d -20-oxosteroids. ° From pregna-4,16-diene-3,20-dione the major product (25%) was the corresponding dihydro[17a,16-c]pyrazole 3 which, however, reacted further to a significant extent and gave 4 (19%) and 5 (3%). When 3/J-acetoxypregna-5,16-dien-20-one was exposed to diazocyclopropane under the same conditions two products resulted the main product 6 was isolated in 64% yield, but in addition 7 was obtained in 15% yield. The latter product results when 6 is attacked by the diazo compound at the carbonyl group. 

The interaction of the complex tetracarbonyldi-fj-chlorodirhodium with cyclopropane and substituted cyclopropanes produced complexes 3 and 4a, ° respectively, with the same dimeric structure. Contrary to the reaction with the platinum complex a five-membered ring 3 or 4120 jjj which both the metal and the carbon of one of the carbonyl groups were incorporated was formed. The cleavage site was the least substituted C —C bond. Analogous products 4c and 4b (75%) were obtained with bicyclo[4.1.0]heptane and phenylcyclopropane, respective-... 

Treatment of 5,5-dimethyl-e /o-4,6-diphenyltricyclo[4.1.0.0 ]heptan-2-one (36) with lithium aluminum hydride in refluxing tetrahydrofuran cleaved the cyclopropane ring with simultaneous reduction of the carbonyl group and produced the substituted en fo-bicyclo[2.2.1]heptan-2-ol 37 in good yield. 

Lithium is the preferred metal for the reductive cleavage of cyclopropane bonds in cyclopropyl ketones. Sodium is less suited for this reaction because it tends to reduce the carbonyl group rather than open the three-membered ring. With sodium the cyclopropane ring in methyl-substituted benzoylcyclopropanes 1 was retained and the benzoyl group reduced to benzyl contrary to lithium which gave rise to the formation of cleavage products. ... 

Kupchan et al. 88a) derived the structure of A-benzoylcycloxo-buxidine-F from the following observations. The UV spectrum showed that 195 is a secondary benzamide having the carbonyl group conjugated with the cyclopropane ring. The IR spectrum revealed its close relationship to A-benzoylcycloxobuxine-F (197) (see p. 50). The PMR spectrum showed the presence of aromatic protons, one amido proton, and other substitution pattern practically identical with that mentioned above 88a). 

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