Cyclopropane addition reactions

Methylene transfer from lodo methylzinc iodide converts alkenes to cyclopropanes The reaction is a stereo specific syn addition of a CH2 group to the double bond... 

Furan and thiophene undergo addition reactions with carbenes. Thus cyclopropane derivatives are obtained from these heterocycles on copper(I) bromide-catalyzed reaction with diazomethane and light-promoted reaction with diazoacetic acid ester (Scheme 41). The copper-catalyzed reaction of pyrrole with diazoacetic acid ester, however, gives a 2-substituted product (Scheme 42). 

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. 

Additions to cyclopropanes can take place by any of the four mechanisms already discussed in this chapter, but the most important type involves electrophilic attack. For substituted cyclopropanes, these reactions usually follow Markovnikov s rule, though exceptions are known and the degree of regioselectivity is often small. The application of Markovnikov s rule to these substrates can be illustrated by the reaction of 1,1,2-trimethylcyclopropane with The rule predicts that the... 

In addition to a-additions to isocyanides, copper oxide-cyclohexyl isocyanide mixtures are catalysts for other reactions including olefin dimerization and oligomerization 121, 125, 126). They also catalyze pyrroline and oxazoline formation from isocyanides with a protonic a-hydrogen (e.g., PhCH2NC or EtOCOCHjNC) and olefins or ketones 130), and the formation of cyclopropanes from olefins and substituted chloromethanes 131). The same catalyst systems also catalyze Michael addition reactions 119a). 

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... 

Addition reactions with alkenes to form cyclopropanes are the most studied reactions of carbenes, both from the point of view of understanding mechanisms and for synthetic applications. A concerted mechanism is possible for singlet carbenes. As a result, the stereochemistry present in the alkene is retained in the cyclopropane. With triplet carbenes, an intermediate 1,3-diradical is involved. Closure to cyclopropane requires spin inversion. The rate of spin inversion is slow relative to rotation about single bonds, so mixtures of the two possible stereoisomers are obtained from either alkene stereoisomer. 

Metal-Catalyzed. Cyclopropanation. Carbene addition reactions can be catalyzed by several transition metal complexes. Most of the synthetic work has been done using copper or rhodium complexes and we focus on these. The copper-catalyzed decomposition of diazo compounds is a useful reaction for formation of substituted cyclopropanes.188 The reaction has been carried out with several copper salts,189 and both Cu(I) and Cu(II) triflate are useful.190 Several Cu(II)salen complexes, such as the (V-f-butyl derivative, which is called Cu(TBS)2, have become popular catalysts.191... 

Other Cyclopropanation Methods. Haloalkylmercury compounds are also useful in synthesis. The addition reactions are usually carried out by heating the organomercury compound with the alkene. Two typical examples are given in Section C of Scheme 10.9. 

Chapter 10 considers the role of reactive intermediates—carbocations, carbenes, and radicals—in synthesis. The carbocation reactions covered include the carbonyl-ene reaction, polyolefin cyclization, and carbocation rearrangements. In the carbene section, addition (cyclopropanation) and insertion reactions are emphasized. Recent development of catalysts that provide both selectivity and enantioselectivity are discussed, and both intermolecular and intramolecular (cyclization) addition reactions of radicals are dealt with. The use of atom transfer steps and tandem sequences in synthesis is also illustrated. 

Here the alkene and pyridine will compete for the carbene at a constant concentration of pyridine the observed pseudo first order rate constant for ylide formation will increase with increasing alkene concentration. A plot of kobs vs. [alkene] will be linear with a slope of kad, which is the rate constant for the carbene/alkene addition reaction affording cyclopropane 5 (Scheme 1). 

Finally, one example of trityl salt analogues in the phase-transfer catalysis is presented. The highly stable triazatriangulenium cations 62 [161, 162] were jnst recently introduced to the phase-transfer chemistry [163], Persistent to strongly basic and nncleophilic conditions, these salts revealed efficient catalytic activity in addition reactions (Scheme 64). Modification of the alkyl side chains on nitrogen allowed matching the fair hydro/lipophilicity with the optimised conditions in the alkylation, epoxidation, aziridination and cyclopropanation reactions. The results are comparable to those of tetrabutylammonium salts and in some cases showed even a better outcome. 

Mono-functionalization of Cyg affords, preferrably, C(l)-C(2) adducts (type a) (Figure 13.3). In some cases, for example, upon nucleophilic cyclopropanations they even represent the exclusively formed monoadducts [1-3,17]. Typical examples of addition reactions that afford monoadducts are epoxidations [18,19], osmylation [9], transition metal complex formations [20, 21], hydrogenation [13, 22], many cycloadditions [1, 2] and additions of nucleophiles [23]. For the formation and the chemical transformation of azahomo[70]fullerenes see also Chapter 12 (Schemes 12.4 and 12.5). 

Finally, addition reactions of the isolable phosphasilylcarbenes (13) to such electron-poor substrates as methyl acrylate, C4F9CH=CH2, and styrene afford cyclopropanes. The additions of 13a to (E)- or (Z)-p-deuteriostyrene are stereospecific, and the competitive additions of 13b to ring-substituted styrenes exhibit nucleophilic selectivity, consistent with singlet, nucleophilic carbene addition (Fig. 7.8). ... 

The synthesis of bicyclo[n. 1.0]alkanes (82) from various 1-chlorovinyl p-tolyl sulfoxides (80) and lithium enolate of ieri-butyl acetate, propionate and hexanoate through the adducts (81) are summarized in Table 3. As shown in Table 3, addition reaction of tert-butyl carboxylates to 1-chlorovinyl p-tolyl sulfoxides (80) proceeds smoothly to afford the adducts (81) in high to quantitative yields. Cyclopropanation of 81 with i-PrMgCl... 

Starting from optically active 1-chlorovinyl p-tolyl sulfoxide derived from 2-cyclohex-enone, the asymmetric synthesis of cyclopropane derivative (85) was realized (equation 23) . Addition reaction of lithium enolate of tert-butyl acetate to 83 gave the adduct (84) in 96% yield with over 99% ee. Treatment of the latter with i-PrMgCl in a similar way as described above afforded optically pure (15,6/ )-bicyclo[4.1.0]hept-2-ene (85) in 90% yield. 

Problem 9.25 Although cyclopropanes are less reactive than alkenes, they undergo similar addition reactions, (fl) Account for this by geometry and orbital overlap, (b) How does HBr addition to 1,1-dimethylcyclopropane resemble Markovnikov addition <... 

One of the most extensively used addition reactions of cyclobutanes is hydrogenolysis.36 With regard to the mechanistic aspect, evidence has been provided that hydrogenolysis of cyclobutane is structure sensitive to the particle size of the platinum on alumina catalysts.37 Moreover, a kinetic study has also revealed that the mechanism for the hydrogenolysis of cyclobutanes is likely to be different from that for cyclopropanes.37... 

In marked contrast to those of cyclopropanes, the addition reactions of cyclobutanes usually require drastic conditions and activating substituents. Notwithstanding these shortcomings, the cleavage of cyclobutanes by addition reactions has been widely employed in the synthesis of organic molecules of moderate complexity. In this section, electrophilic addition, as well as nucleophilic addition, of cyclobutanc derivatives are reviewed with the aim of demonstrating their synthetic profile. 

---