Cyclopropanones 4 + 3 cycloaddition reactions

Further analysis of the microwave spectra provides a precise description of the bond lengths and angles (Table 7). The C2C3 bond is unusually long and relatively weak as shown by the reactivity of substituted cyclopropanones in cycloaddition reactions (see Section 4.4). The carbon-oxygen bond is somewhat shorter than the average carbonyl group and this feature is reflected in the infrared properties of cyclopropanones outlined below. 

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>... 

Other 4 +3- 7 cycloaddition reactions of cyclopropanones with dienes are listed in Table 23. Of particular interest is the reaction of 2,2-dimethylcyclopropanone with N-methylpyrrole to give the tropane alkaloid 150. 121>... 

Cyclopropanones act as three-carbon sources in [4 + 3] cycloadditions. However, these small-ring compounds are impractical for preparative scale experiments, because they are generally inaccessible and also must be handled with special precautions, in contrast to other oxyallyl species. One of the early descriptions of the synthesis of cyclopropanones appeared in 1932. NeverAeless, the development of the chemistry of cyclopropanones proceeded at quite a slow pace until the late 1960s when Turro reported their utilization in [4 -i- 3] cycloaddition reactions. 2,2-Dimethylcyclopropanone (14) adds to furan, cyclopentadiene, 6,6-dimethylfulvene and the relatively nucleophilic N-methylpyrrole to give the corresponding cycloproducts, but fails to react with anthracene and 1,3-butadiene. Parent cyclopropan-one cannot be used. 

Translation of these results into compound I leads to structure X. Unraveling of the strained zwitterion XI derived from this would yield keto aldehyde XII, a structure that plays a central role in the various possible reaction mechanisms that branch off from the starting material I. Furthermore, under photo-lytic conditions, some alkenes react with carbonyl compounds to form four-membered cyclic ethers, namely, oxetanes, by way of a [2-1-2] cycloaddition reaction known as the Patemo-Buchi process. Such a reaction would be all that is necessary to convert XII into the bicyclic cyclopropanone XIII required for the Favorskii-type rearrangement (see Scheme 42.3). Splitting by methanol attack would directly yield compound II. 

Cyclopropanone ketals undergo a unique [2s + 2a] cycloaddition reaction with tetracyanoethylene (TCNE) ". In the case of cis- and trans-dimethyl 0,S ketals 151... 

It is quite a critical question to know whether the cyclopropanone and the zwitterion are mesomeric forms, or two real chemical species in equilibrium with each other. According to Burr and Dewar the unsubstituted zwitterion is not a mesomeric representation of the unsubstituted cyclopropanone in fact, the zwitterion is an individual chemical species which is the precursor of the cyclopropanone, Unfortunately, there is no experimental proof of this hypothesis as cycloaddition reactions are not observed when nonsubstituted cyclopropanones are interacted with dienophiles. It should be noted that this kind of cycloaddition reaction probably proceeds via a dipolar mechanism. ... 

However, evidence for the existence of a zwitterionic intermediate has been obtained by Bordwell when the zwitterion is substituted. In this case, Bordwell assumed an equilibrium between the zwitterion and the corresponding cyclopropanone. This was confirmed by Fort, who was able to trap the zwitterion by a cycloaddition reaction. 

Ketenes rarely produce [3+ 2]-cycloaddition products with diazo compounds. The reaction possibilities are complex, and nitrogen-free products are often obtained (5). Formation of a cyclopropanone represents one possibihty. Along these lines, the synthesis of (Z)-2,3-bis(trialkylsilyl)cyclopropanones and (Z)-2-trialkylsilyl-3-(triethylgermyl)cyclopropanones from diazo(trialkylsilyl)methanes and appropriate silyl- or germylketenes has been reported (256,257). It was found that subsequent reaction of the cyclopropanone with the diazoalkane was not a problem, in contrast to the reaction of diazomethane with the same ketenes. The high cycloaddition reactivity of diazomethylenephosphoranes also extends to heterocumulenes. The compound R2P(C1)=C=N2 (R = N(/-Pr)2) reacts with CS2, PhNCO and PhNCS to give the corresponding 1,2,3-triazole derivative (60). 

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. 

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 ... 

The first example of a product from a 4 + 3- -7 cycloaddition of a cyclopropanone was provided by Fort 119>, who isolated the bicyclic ketone 37 from the reaction of a-chlorodibenzyl ketone with 2,6-lutidine in the presence of furan. Cookson and Nye 40> isolated 37 from the reduction of bis- a-bromobenzyl ketone with sodium iodide in the presence of furan, and also obtained the corresponding adduct with cyclopentadiene. The... 

The third type of cycloaddition results from the reaction of cyclopropanones with activated olefins. For example, dimethylketene adds to methyl substituted cyclopropanones affording the spiro lactones 153 a—c. 96,n8,i22b) Similarly the ortho ester 154 is formed from 1,1-dimethoxy-ethylene and 2,2-dimethylcyclopropanone 154 dimerizes to 155 upon standing. ng>... 

Irradiation of tetramethylcyclobutanedione (16) in furan gives an 8-oxabicyclo[3.2.1]oct-6-en-3-one derivative via oxyallyl cation (17). This reaction is the first example of the cycloaddition of cyclopropanones. Although the syntheses of a few seven-membered ring compounds have been subsequently carried out by means of this photoreaction, interest in cyclopropanone chemistry has been directed to structure and reactivity relationships, but not to organic synthesis. ... 

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. 

Dehalogenation has provided routes to cyclopropanones which may then be trapped in the form of hemiketals or cycloaddition products. Thus, electrolytic reduction of l,3-dibromo-2-propanones served as a method for preparing the derivatives 6 and 7 as shown in equation 2. In a related reaction, treatment of a,a -dibromobenzyl ketone with sodium iodide in acetone in the presence of furan yielded the cycloadduct 8 (equation 3) . 

A 1,3-dibromo ketone was also reductively cyclized with lithium dimethylcuprate in diethyl ether, containing furan, to form tetramethylcyclopropanone by a two-electron reduction and subsequent addition of the cuprate across the reactive carbonyl function to give 34. Side products include 2,2,4-trimethylpentan-3-one and the [3-f4] cycloaddition product of the cyclopropanone with furan. An ethereal medium is a requirement, since the same reaction in pentane at — 50°C did not lead to cyclopropane derivatives. More detailed information on the in situ generation of cyclopropanenes and subsequent addition of nucleophiles is given in Section 1.1.3.3. 

Besides the addition of classical reagents to cyclopropanones vide supra), there are some reactions of cyclopropanones which lead to functionalized cyclopropanes via such reactions as cycloadditions with various reagents. Cycloadditions of the 2 + 2 - 4 type with the carbonyl moiety of 2,2-dimethylcyclopropanone (1) and dimethylketene and 1,1-dimethoxyethene give spiro compounds 2 and 3, respectively. ... 

This looks as though each of the C—C bonds is independently the result of both HOMO/LUMO interactions, with an endo selectivity as well. In the presence of dienes, these species behave as allyl cations (see p. 259) and undergo clean [4 + 2] cycloadditions, as in the reaction of the oxyallyl 6.372 giving the tricyclic ketone 6.373, which is similar to the diene 6.369. Normally, oxyallyls are in equilibrium by disrotatory electrocyclic ring closures with cyclopropanones and with allene oxides, but the presence of the five-membered ring in these particular examples makes these pathways counter-thermodynamic. 

Possible pathways to the pyridopyridazinones are shown in Scheme 3. One route (path a) involves initial 1,3-dipolar cycloaddition of the JV-imine with the cyclopropenone and subsequent opening of the cyclopropanone ring with transfer of the amino hydrogen to afford 41. An alternate route (path b) is very similar to that proposed for the reaction with 2//-azirines (Section IV,A,6). 

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