Cyclopropane 1,1-difluorocyclopropane

Dolbier WR, Sellers SF (1982) J. Am. Chem. Soc. 104 2494. A review of the authors works on thermal rearrangements of gem-difluorocyclopropanes covering, inter alia, cyclopropane thermolysis, methylene cyclopropane and spiropentane rearrangements, vinyl-cyclopropane and cyclopropylcarbinyl isomerizations has been published Dolbier WR (1981) Acc. Chem. Res. 14 195... 

Methylene difluorocyclopropanes are relatively rare and their rearrangement chemistry has been reviewed recently [14]. In addition, electron deficient alkenes such as sesquiterpenoid methylene lactones may be competent substrates. Two crystal structures of compounds prepared in this way were reported recently [15,16]. Other relatively recent methods use dibromodifluoromethane, a relatively inexpensive and liquid precursor. Dolbier and co-workers described a simple zinc-mediated protocol [17], while Balcerzak and Jonczyk described a useful reproducible phase transfer catalysed procedure (Eq. 6) using bromo-form and dibromodifluoromethane [18]. The only problem here appears to be in separating cyclopropane products from alkene starting material (the authors recommend titration with bromine which is not particularly amenable for small scale use). Schlosser and co-workers have also described a mild ylide-based approach using dibromodifluoromethane [19] which reacts particularly well with highly nucleophilic alkenes such as enol ethers [20], and remarkably, with alkynes [21] to afford labile difluorocyclopropenes (Eq. 7). 

Difluorocyclopropane has a lengthened distal C2-C3 (1.533 A), and shortened proximal C1-C2, C1-C3 bonds (1.464 A) in comparison with cyclopropane (1.514 A).3 In all other fluorinated cyclopropanes for which data is available, all of the ring bonds are slightly shorter than those of cyclopropane. Data for fluorocyclopropane is not available, but the crude assumption is that the distal C2-C3 bond has an average value between that of 1,1-difluorocyclopropane... 

The chemical effect of a gem-difluoro group on cyclopropane is to facilitate the thermal cleavage of the distal ring bond. This is illustrated by the facile endojexo isomerization of tricyclic cTO-difluorocyclopropane 1, which occurs at 60 C.4... 

The cis/trans isomerization of l,l-difluoro-2,3-dimethylcyclopropane (2) has an activation energy about lOkcal mol-1 lower than that of the parent hydrocarbon.5 Unlike the parent hydrocarbon, competing cyclopropane to propene rearrangement is not observed, a generalization that extends to other gem-difluorocyclopropanes studied in the Dolbier laboratories.1... 

The increasing tendency toward thermal extrusion of CF2 with increasing number of fluorine substituents on the cyclopropane ring has been demonstrated in studies of 1,1-difluorocyclo-propane, 1,1,2-trifluorocyclopropane, 1,1.2,2-tetrafluorocyclopropane,19 and perfluorocyclo-propane.20 Studies of the thermolysis of 1,1,2,2-tetrafluorospiropentane 8 21 and 1,1.2,2-tetra-fluoro-3-methylenecyclopropane (25),22 however, demonstrated that the CF2-CF2 bond in a tetrafluorocyclopropane is substantially weakened. In the case of 25, rearrangement to 2-(di-fluoromethylene)-l,l-difluorocyclopropane (26) occurs irreversibly at 150°C at a rate that was calculated to be 7850 times faster than that of the gem-difluoro analog 21. 

While the cyclopropane to propene isomerization is not observed in the thermal rearrangements of gem-difluorocyclopropanes (vide supra), this is the principal reaction of polyfluorocy-clopropanes in the presence of Lewis acids.23 Perfluoro(alkylcyclopropanes) 27 isomerize to perfluoroalkenes 28 in high yield, despite the harsh conditions (100°C) required in some cases. It should be noted that double-bond migration under these reaction conditions occurs readily (see Section 5.1.2.2.). 

Difluoro(methylene)cyclopropanes have been obtained in modest yields from allene by difluorocarbene addition.61 The difluorocyclopropane moiety proved stable upon... 

This rather unusual reaction is possible because of the exceptional stability of the CF- biradical. All fluorinated cyclopropanes, above 1,1-difluorocyclopropane, appear to follow a similar reaction mechanism . 

Next we focus on fluorinated cyclopropanes where we discuss, for example, the fact that 1,1-difluorocyclopropane and hexafluorocyclopropane show unusual behavior which in part or whole reflects extra strain. Contrariwise, cyclopropanes and other strained molecules substituted by perfluoroalkyl groups such as CF3 are anomalously stable despite having some slight extra strain. 

The strain energy of methylenecyclopropane (2) exceeds" that of cyclopropane by about 13 kcal mol "S a value similar to the excess strain in 1,1-difluorocyclopropane. This is certainly a part of the propensity for ring-opening although the stability of trimethylene-methane (3) is undoubtedly the more important factor (cf. equation 3). Similarly, the ringopening facility of cyclopropanone (see Chapter 23 by Wasserman and coworkers) partially reflects additional ring strain. 

In the presence of more conventional bases carbene production is supressed. The decomposition of the chlorodifluoromethyl anion has been shown to be reversible and the yield of difluorocyclopropane is increased by increasing the alkene concentration. Epoxides upon treatment with dichlorocarbene afford cyclopropanes stereospecific-ally. The reaction proceeds by stereospecific deoxygenation of the epoxide to give olefin (41) which is subsequently trapped by the carbene. 

Higher fluoroalkenes and difluorocyclopropanes are also sources of CF2. Dalby (59) obtained this radical by the flash photolysis of perfluoropropylene. The kinetics of CF2 formation from the thermal decomposition of perfluorocyclopropane at 526° - 549°K were reported by Atkinson and McKeagan (78). Birchall, Haszeldine and Roberts (79) investigated the thermal decomposition of a series of gem-difluorohalocyclopropanes as sources of CF2. The cyclopropanes studied were placed in the following approximate order of decreasing stability toward CF2 elimination ... 

Introduction of the cyclopropane group into DDT chemistry was first tried in 1944 but l,l-bis-( -chlorophenyl)-cyclopropane is essentially inactive (Musca 7500, Culex 1.0). However, the corresponding l,l-di-( -chlorophenyl)-2,2-dichloro-cyclopropane (11) (Musca 12.0, Culex 0.042) is ap( i ximately as toxic as DDD (, whose configuration it approximates. The corresponding l,l-di-( -chlorophenyl)-2-chlorocyclopropane was about one-tenth as active and in agreement with the trihaloethanes the 2,2-difluorocyclopropane (Musca 415) was of low activity, the 2,2-dibromocyclopropane (Musca 365) only slightly more active, while the 2-chloro-2-fluoro (Musca 60) and 2-chloro-2-bromocyclopropane were intermediate . ... 

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