Cyclopropanone, addition reaction

The method that is used in the present preparation is based upon the formal concept of employing cyclopropanone in an aldol condensation with an eholate of another ketone. The resulting aldolate exhibits characteristics of a "homoenolate" and may undergo a second carbonyl addition reaction to form a five-membered ring as suggested in the following generalized pathway ... 

Introduction by addition reactions a. Addition of amines to cyclopropanones... 

The addition of ammonia and amines to cyclopropanone provides carbinol amines which may undergo further reaction to form more complex products, as shown in Scheme 8. In some cases, the initially formed carbinol amines may be isolated, as in the case of 1-piperidino and 1-morpholino cyclopropanol. The further reaction of these derivatives appears to take place through cyclopropyl iminium salts (Scheme 9). The nature of the product formed in these imine addition reactions depends significantly on the reaction conditions. Thus, with cyclopropanone and excess aniline at low temperature, the simple addition product is formed almost quantitatively . However, at 25°C, both monoanilino and the dianilino derivatives are formed (equation 16) . 

The Favorskii rearrangement will not be treated in detail here because, in general, it does not lead to isolable cyclopropanones. Additions to cyclopropanones are treated amongst the reactions of cyclopropanes, while the Favorskii rearrangement has been reviewed extensively in the literature. ... 

With bulkier alkoxides, e. g. potassium ter/-butoxide in fcrr-butyl alcohol or potassium (4-chlorophenyl)dimethylcarbinolate, a-bromo ketone 16 is converted into rra x-2,3-di-/cr/-butyl-cyclopropanone (17). Addition of methanol or 2-propanol to cyclopropanone 17 at 25 °C gives a fast addition reaction resulting in hemiacetal 21, which slowly undergoes ring opening at 80 °C in methanol to give a-methoxy ketone 22 (R = Me). ... 

The reaction of lithium aluminum hydride with cyclopropanones, e. g. trans-2, i-6 -tert-h xiy -cyclopropanone (l)A 2-(trimethylsilyl)cyclopropanone (3) ° and 2-(trialkylgermyl)cyclo-propanone (5, Me = Ge)A ° gave rise to the 1,2-addition products which, upon aqueous workup, delivered cyclopropanols 2, 4, and 6. Under forcing conditions the addition reaction may be followed by ring opening. 

The most general entry into functionalized sulfur-containing cyclopropanes is the addition reactions of cyclopropanones and thiols (see Section 5.2.3.5.4.). Thus, reaction of cyclo-propanone with thiols in dichloromethane affords l-(alkylsulfanyl)cyclopropanols 39 which are readily transformed into the corresponding cyclopropyl bromides 40 and cyclopropyl chlorides 41 upon reaction with anhydrous hydrogen bromide and hydrogen chloride, respectively. ... 

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... 

Also, both [3 + 4] cycloadditions of cyclopropanone to dienes and [3 + 2] additions to carbonyl groups have been observed. These reactions seem easiest to understand if cyclopropanone can behave as if it had, or could be converted to, a dipolar open-chain structure ... 

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)... 

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)... 

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... 

Other hemiacetals which have been prepared include the methyl 8<9a>, ethyl 9b), and isopropyl hemiacetals 81) of tetramethylcyclopropanone, the phenyl, a- and (3-naphthyl hemiacetals of cyclopropanone 82>, and the benzyl hemiacetal of 2,3-di-f-butylcyclopropanone. 13> In the last case, the benzylic methylene protons display an AB pattern in the PMR spectrum indicating that the two Ybutyl groups are trans to one another. Although derivatization of this di-f-butyl ketone was possible, carbonyl addition may be hindered by steric factors as suggested by the lack of reaction of 2,2-diY-butylcyclopropanone with methanol. 55a>... 

The reaction of cyclopropanone with hydrogen chloride affords the chlorohydrin 90 (65%). 5 15) Acetylation of 90 with ketene gives the expected acetoxy compound 91 (34%) while the addition of methanol to a methylene chloride solution of 90 affords cyclopropanone methyl hemiketal (100%). The latter reaction illustrates the use of 91 as an in situ source of cyclopropanone. 

N-Methylaniline adds to cyclopropanone to give the expected carbinol amine in quantitative yield. 5-90> On the other hand, a mixture of addition products may be isolated from the reaction of cyclopropanone 5>90> or cyclopropanone ethyl hemiketal4) with aniline (Scheme 18). At — 78°C, the carbinol amine 104 (66%) and the dimeric species 105 (33%) were obtained when the reactants were present in stoichiometric amounts. With excess aniline, 104 was produced almost quantitatively. However, at 25 °C, both 104 and the dianilino product 106 were obtained. These products could be interconverted by the addition of aniline or cyclopropanone, respectively. At 125 °C, o-propionylaminopropiophenone (107) was formed, possibly by further reaction of the carbinol amine with cyclopropanone as shown. 4>... 

Other alkylation reactions are observed in the condensation of cyclo-propanium ions (generated in situ) with ketones 89.92)> enamines6, nitroalkanes 93>, dimethylmalonate 92>, and phenol. 92> Thus, 7-hydroxy-7-pyrrolidinobicyclo[4.1.0]heptane (56) as well as the 7,7-dipyrrolidino derivative (54) react with acetone to give the amino ketone 113. 89> This reaction may be pictured as an addition of the enol form of the ketone to the reactive iminium salt formed from the carbinol amine. In like manner, phenol undergoes ortho substitution with the carbinol amine 114 formed from cyclopropanone and dimethyl amine. 

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. 

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)... 

In accord with their unusually high reactivity, cyclopropanones may undergo various types of cycloaddition reactions. In addition to Diels-Alder type addition with conjugated dienes (4+3- 7 cycloadditions), substituted cyclopropanones also react with aldehydes forming dioxo-lanes (3 +2->-5), and with ketenes yielding (3-lactones (2 +2- 4).118>... 

Cyclopropanone ethyl hemiacetal is a molecule of considerable interest since its reactions appear to involve the formation of the labile cyclopropanone.7 It readily undergoes nucleophilic addition of Grignard reagents,4,5 azides,4 and amines5 to provide 1-substituted cyclopropanols in high yields. It has been reported that upon treatment with an equimolar amount of methylmagneslum iodide, the cyclopropanone ethyl hemiacetal is... 

What is happening here is that the oxyallyl cation is in equilibrium with the cyclopropanone by an electrocyclic reaction (Chapter 36) and the alcohol is capturing this unstable ketone by nucleophilic li addition. Hemiacetals of cyclopropanones form spontaneously in alcoholic solution (Chapter 6)... 

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