Reactive cyclopropane species

Figure 15.8 The Bingel reaction for the modification of fullerenes involves the in situ formation of a reactive halogen species in the presence of the strong base DBU. The cyclopropanation product can be used to create many bioconjugates.

The second major advantage of this method is that a wide range of new cyclopropanating reagents with new properties became available. If a sufficiently acidic compound reacts with diethylzinc, a mixed zinc species is formed (equation 5). The second ethyl group can then be exchanged with an iodomethyl unit to generate a potentially reactive iodomethylzinc species. 

Simmons-Smith cyclopropanation proceeds via the addition of a zinc carbenoid (6/8) to an olefin. There are three classes of reactions, however, that can generate the reactive zinc species, each with it is own mechanistic pathway. The oxidative addition of an activated form of zinc metal into a C-X bond is by far the most widely used method for the formation of 6... 

Various cyclopropanated molecules such as chrysanthemic acid, and pyrethrins are well known as nonpolluting insecticides, and one of the synthetic routes to these biologically active compounds appeals to the copper or rhodium catalyzed decomposition of diazo esters to promote the generation of the reactive carbenoid species [103]. 

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-... 

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. 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

From the point of view of both synthetic and mechanistic interest, much attention has been focused on the addition reaction between carbenes and alkenes to give cyclopropanes. Characterization of the reactivity of substituted carbenes in addition reactions has emphasized stereochemistry and selectivity. The reactivities of singlet and triplet states are expected to be different. The triplet state is a diradical, and would be expected to exhibit a selectivity similar to free radicals and other species with unpaired electrons. The singlet state, with its unfilled p orbital, should be electrophilic and exhibit reactivity patterns similar to other electrophiles. Moreover, a triplet addition... 

Cyclopropanation with Halomethylzinc Reagents. A very effective means for conversion of alkenes to cyclopropanes by transfer of a CH2 unit involves reaction with methylene iodide and a zinc-copper couple, referred to as the Simmons-Smith reagent.169 The reactive species is iodomethylzinc iodide.170 The transfer of methylene occurs stereospecifically. Free CH2 is not an intermediate. Entries 1 to 3 in Scheme 10.9 are typical examples. 

Where we have reason to suspect the involvement of a particular species as a labile intermediate in the course of a reaction, it may be possible to confirm our suspicions by introducing into the reaction mixture, with malice aforethought, a reactive species which we should expect our postulated intermediate to react with particularly readily. It may then be possible to divert the labile intermediate from the main reaction pathway—to trap it—and to isolate a stable species into which it has been unequivocally incorporated. Thus in the hydrolysis of trichloromethane with strong bases cf. p. 46), the highly electron-deficient dichlorocarbene, CClj, which has been suggested as a labile intermediate (p. 267), was trapped by introducing into the reaction mixture the electron-rich species cis but-2-ene (11), and then isolating the resultant stable cyclopropane derivative (12), whose formation can hardly be accounted for in any other way ... 

Cyclopropanones are also reactive toward certain types of cycloadditions. Theoretical modeling indicates that a dipolar species resulting from reversible cleavage of the cyclopropanone ring is the reactive species.96 cis-Disubstitutcd cyclopropanes with bulky substituents exhibit NMR features that indicate a barrier of 10-13 kcal/mol for... 

Of the cyclopropanation reactions studied, the reaction between styrene and ethyl diazoacetate has become the benchmark for determining the utility of a bis(oxazoline) ligand in cyclopropanations. In 1990, Masamune and co-workers introduced several bis(oxazoline) ligands including 2 and 35-40 as catalysts for the cyclopropanation of styrene with ethyl diazoacetate. The reactive species in these reactions were determined to be the bis(oxazoline) dimers of type 2a and 38a-40a, as shown in Figure 9.10. 

In cyclopropane carboxylates the ring strain influences the acidity of the a-carbon, thus the enolates are more difficult to prepare and once made, are more reactive than in the higher-inem-bered rings. These enolates probably do not have an enolate structure, but rather are a-metal-lated species. 

The large difference in reactivity between cyclopropanes and cyclobutanes toward most electrophiles arises because there is little strain relief in the rate-determining step. The cleavage of C-C bonds by transition metal species leads to metallocy-cloalkanes, and if cleavage proceeds to a significant extent in the rate-determining step, the reactivities of cyclopropanes and cyclobutanes should become more comparable. 

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