Carbenes addition-fragmentations

An important synthetic application of this reaction is in dehalogenation of dichloro- and dibromocyclopropanes. The dihalocyclopropanes are accessible via carbene addition reactions (see Section 10.2.3). Reductive dehalogenation can also be used to introduce deuterium at a specific site. The mechanism of the reaction involves electron transfer to form a radical anion, which then fragments with loss of a halide ion. The resulting radical is reduced to a carbanion by a second electron transfer and subsequently protonated. 

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

Another approach to substituted bicyclopropylidenes is by carbene addition onto butatrienes and alkenylidenecyclopropanes bringing the substituents in with the allene or with the carbene moiety as well as with both fragments. This way, Skattebol et al. [41] and later Kostikov et al. [42] have prepared tetrahalote-... 

The carbene derived by metal-catalysed decomposition of ethyl diazoacetate attacks alkenes to introduce a two-carbon fragment into a cyclopropane—an industrial synthesis of ethyl chrysanthe-mate, a precursor to the pyrethrin insecticides (see p. 000), uses this reaction. The diene in the starting material is more nucleophilic (higher-energy HOMO see Chapter 20) than the single alkene in the product, so the reaction can be stopped after one carbene addition. 

Carbanions can exist as metal salts, and are also important intermediates in reactions carried out under basic conditions. They react as strong bases and nucleophiles, undergoing hydrogen abstraction reactions, nucleophilic substitution and addition, fragmentation, and loss of halide ions to give carbenes, They can be identified spectroscopically or by trapping. 

Corey s method20 relies on metal exchange with the bromocyclopropane 69 prepared by carbene addition. The extra stabilisation of cyclopropyl anions (chapter 8) makes both this lithium derivative and the ylid 63 more easily handled. Addition to aldehydes or ketones gives mixtures of adducts 70 [it turns out that none of the stereochemistry of 69 or 70 matters] which fragment under Lewis acid catalysis to give the thioacetal 71. Careful hydrolysis releases the 3,4-enal -72, the product of a homoaldol reaction with an aldehyde homoenolate and RCHO and a difficult compound to make as the double bond moves into conjugation very easily. 

The 1,3-dipolar cycloadditions are a powerful kind of reaction for the preparation of functionalised five-membered heterocycles [42]. In the field of Fischer carbene complexes, the a,/ -unsaturated derivatives have been scarcely used in cyclo additions with 1,3-dipoles in contrast with other types of cyclo additions [43]. These complexes have low energy LUMOs, due to the electron-acceptor character of the pentacarbonyl metal fragment, and hence, they react with electron-rich dipoles with high energy HOMOs. 

Seven-membered carbocycles are also available from the reaction of alkenylcarbene complexes of chromium and lithium enolates derived from methyl vinyl ketones [79b] (Scheme 65). In this case, the reaction is initiated by the 1,2-addition of the enolate to the carbene complex. Cyclisation induced by a [1,2]-migration of the pentacarbonylchromium group and subsequent elimination of the metal fragment followed by hydrolysis leads to the final cyclo-heptenone derivatives (Scheme 65). 

Lappert has described the three-fragment oxidative addition of (halomethylene) dimethylammonium halides to Ru and Ir ds complexes (62,72). The products are compounds containing the secondary carbene ligand CHNMe2, e.g.,... 

It was proposed that electrophilic addition of a metal carbene rather than direct insertion or fragmentation of an initially formed 2-azabicyclo[3.1.0]hex-3-ene accounts for the formal insertion products 239) (Scheme 33). 

In addition, 18-19% of isobutene and chloroacetylene formed via fragmentation. Photolysis of the diazirine in up to 9 M trimethylethylene in pentane led to a sharp decrease in 27 and 28 (to 32% and 8.5%), along with 40% of cyclopropanes formed via the capture of 19. However, the yield of isobutene and chloroacetylene was unchanged, indicating that these products did not stem from the carbene, but arose directly by fragmentation of its excited diazirine precursor.45... 

The olefin binding site is presumed to be cis to the carbene and trans to one of the chlorides. Subsequent dissociation of a phosphine paves the way for the formation of a 14-electron metallacycle G which upon cycloreversion generates a pro ductive intermediate [ 11 ]. The metallacycle formation is the rate determining step. The observed reactivity pattern of the pre-catalyst outlined above and the kinetic data presently available support this mechanistic picture. The fact that the catalytic activity of ruthenium carbene complexes 1 maybe significantly enhanced on addition of CuCl to the reaction mixture is also very well in line with this dissociative mechanism [11] Cu(I) is known to trap phosphines and its presence may therefore lead to a higher concentration of the catalytically active monophosphine metal fragments F and G in solution. 

DFT calculations confirmed the similarities with the alkyne/vinylidene transformation but have revealed that additional parameters were essential to achieve the isomerization [8, 20-23]. The hydride ligand on the 14-electron fragment RuHC1L2 opens up a pathway for the transformation similar to that obtained for the acetylene to vinylidene isomerization. However, thermodynamics is not in favor of the carbene isomer for unsubstituted olefins and the tautomerization is observed only when a re electron donor group is present on the alkene. Finally the nature of the X ligand on the RuHXL2+q (X = Cl, q=0 X = CO, q=l) 14-electron complex alters the relative energy of the various intermediates and enables to stop the reaction on route to carbene. 

On the other hand, complexes with weak Jt interaction between the metal and the carbene will have an energetically low-lying K orbital. In addition to this, electron-transfer from the metal to C will be less efficient, thus leading to a more positively charged carbene fragment. Hence, carbene complexes with a large energy gap and poor orbital overlap between the metal d orbital and the carbene 2 p orbital will be prone to react with nucleophiles. 

The carbene-bound alkyl groups are acidic pX [(CO)5Cr=C(OMe)Me in H2O] 12.3 and can be easily deprotonated and alkylated [45,211,212] or acylated [213] (Figure 2.16). Stereoselective aldol-type additions can be realized with the aid of Fischer-type alkylcarbene complexes [214-216]. In these reactions the metallic fragment can either play the role of a bulky carbonyl group or stabilize a given conformation of the substrate by chelate formation [216,217]. 

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