Cyclopropanes reactivity

In order to sec the influence that a trifluoromethyl substituent has on cyclopropane reactivity, l-(trifluoromethyl)-2-vinylcyclopropane (18) was prepared and its thermal reactions studied.13 Both the cisitrans isomerization and the vinylcyclopropane rearrangement were slower than those of any 2-substituted vinylcyclopropane previously reported. When m-18 is heated at 275 C, a clean and reversible cisitrans isomerization takes place (Kequi, = 5.33). At 332-364 C, 18 undergoes normal vinylcyclopropane rearrangement to 4- and 3-(tri-fluoromethyl)cyclopentenc (19) and (20). respectively. 

A special note about nomenclature is in order. Both the terms carbene and alkylidene complex have come into use, and attempts have been made to use these terms to differentiate various types of reactivity of these species. However, the term carbene complex is used throughout this chapter, primarily because of the emphasis on cyclopropanation reactivity. 

More recently, the bis-cyclopropanation reactivity has also been observed to make highly strained cyclopropyl-substituted diquinane frameworks in a completely diastereoselective manner [82] (Scheme 43). It is noteworthy that the formal metathesis product was also observed in these reactions, albeit as a minor product, and that the simple introduction of a methyl group on one ene partner was quite troublesome. 

It is important to remember that the major electron density is on the edges of the cyclopropane rings, not in the middle of the ring. The cyclopropane MO with large density in the middle of the ring formed from the ufout) group orbitals is too low-lying to be important in cyclopropane reactivity. 

Whenever functional groups are connected with a C=C double bond, their reactivity is often relayed through that double bond. Analogous rules can be applied to the corresponding cyclopropane derivatives. 

Historical Inhalation Agents. Diethyl ether produces excellent surgical anesthesia, but it is flammable (see Ethers). Chloroform is a nonflammable, sweet smelling, colorless Hquid which provides analgesia at nonanesthetic doses and can provide potent anesthesia at 1% (see Chlorocarbons AND CHLOROHYDROCARBONs). However, a metabohte causes hepatic cell necrosis. Tdlene, a nonflammable colorless Hquid, has a slower onset and recovery and a higher toxicity and chemical reactivity than desirable. Cyclopropane is a colorless gas which has rapid induction (2 —3 min) and recovery characteristics and analgesia is obtained in the range of 3—5% with adequate skeletal muscle relaxation (see Hydrocarbons). The use of cyclopropane has ceased, however, because of its flammabiHty and marked predisposition to cause arrhythmias. 

In solutions of n-propyllithium in cyclopropane at 0°C, the hexamer is the main species, but higher aggregates are present at lower temperatures. The reactivity of the organo-... 

The behavior of strained,/Zuorimiret/ methylenecyelopropanes depends upon the position and level of fluorination [34], l-(Difluoromethylene)cyclopropane is much like tetrafluoroethylene in its preference for [2+2] cycloaddition (equation 37), but Its 2,2-difluoro isomer favors [4+2] cycloadditions (equation 38). Perfluoromethylenecyclopropane is an exceptionally reactive dienophile but does not undergo [2+2] cycloadditions, possibly because of stenc reasons [34, 45] Cycloadditions involving most possible combinations of simple fluoroalkenes and alkenes or alkynes have been tried [85], but kinetic activation enthalpies (A/f j for only the dimerizations of tetrafluoroethylene (22 6-23 5 kcal/mol), chlorotri-fluoroethylene (23 6 kcal/mol), and perfluoropropene (31.6 kcal/mol) and the cycloaddition between chlorotnfluoroethylene and perfluoropropene (25.5 kcal/mol) have been determined accurately [97, 98] Some cycloadditions involving more functionalized alkenes are listed in Table 5 [99. 100, 101, 102, 103]... 

Boche, G, Walborsky, H M In Cyclopropane Derived Reactive Intermediates, Fatal, S, Rappoport, Z, Eds, John Wiley Chichester, 1990, Chapter 1... 

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

Although the rationalization of the reactivity and selectivity of this particular substrate is distinct from that for chiral ketals 92-95, it still agrees with the mechanistic conclusions gained throughout the study of Simmons-Smith cyclopropa-nations. StOl, the possibility of the existence of a bimetallic transition structure similar to v (see Fig. 3.5) has not been rigorously ruled out. No real changes in the stereochemical rationale of the reaction are required upon substitution of such a bimetallic transition structure. But as will be seen later, the effect of zinc iodide on catalytic cyclopropanations is a clue to the nature of highly selective reaction pathways. A similar but unexplained effect of zinc iodide on these cyclopro-panation may provide further information on the true reactive species. 

Examination of cyclopropanation through RT6 and RT7 reveals that a less conventional explanation may be required to rationalize the high reactivity of zinc car-benoids (Fig. 3.29). The structure of RT6 represents a pseudo-dimer as shown in RTS that has been further activated by coordination of zinc chloride to the oxygen of the chloromethylzinc alkoxide. This mode of activation is reminiscent of that observed in RTl. Cyclopropanation proceeding from RT6 through TS3 has an activation energy of 27.8 kcal mol . This represents a negligible decrease in the barrier to methylene transfer when compared to reaction from RTS. 

The activation energy for the favored transition state TS4 (22.8 kcal mol ) is still somewhat high. Still, the qualitative predictions of enhanced reactivity of the zinc alkoxide-zinc chloride complexes are in full agreement with contemporary ideas about this reaction and represent a major advance in the theoretical understanding of the cyclopropanation process. 

Physical properties of cycloalkanes [49, p. 284 50, p. 31] show reasonably gradual changes, but unlike most homologous series, different members exhibit different degrees of chemical reactivity. For example, cyclohexane is the least reactive member in this family, whereas both cyclopropane and cyclobutane are more reactive than cyclopentane. Thus, hydrocarbons containing cyclopentane and cyclohexane rings are quite abundant in nature. 

Yet another kind of alkene addition is the reaction of a carbene with an alkene to yield a cyclopropane. A carbene, R2C , is a neutral molecule containing a divalent carbon with only six electrons in its valence shell. It is therefore highly reactive and is generated only as a reaction intermediate, rather than as an isolable molecule. Because they re electron-deficient, carbenes behave as electrophiles and react with nucieophiiic C=C bonds. The reaction occurs in a single step without intermediates. 

---