1.1- Elimination reactions, carbenes from

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Diamino-substituted complexes of type 37 were first obtained by Fischer et al. [12] in two steps via the 1,2-addition-elimination product 34 from di-methylamine and 35 (Scheme 6). The (3-aminoallenylidene)chromium complexes 36, which can be prepared either from 33 [47,48] or directly from 35 [33], can also be transformed to l,3-bis(dialkylamino)-substituted complexes of type 37 (e.g., R2=z Pr) by treatment with dimethylamine in excellent yields [33]. Although the complex 37 is accessible by further reaction of the complex 34 with dimethylamine, and 34 itself stems from the reaction of 35 with dimethylamine, the direct transformation of 33 to 37 could not be achieved [12]. In spite of this, heterocyclic carbene complexes with two nitrogens were obtained by reactions of alkynylcarbene complexes 35 with hydrazine [49] and 1,3-diamines [50]. 

The reactions of dichlorocarbene with phosphorus ylides result in the corresponding olefins and phosphines.66-68 In the reaction of dichlorocarbene generated in situ with tributyl- and triphenylmethylenephosphoranes or triphenylethylidenephosphorane, the olefin yield increases as the nucleo-philicity of phosphorus ylide increases. According to,67 the reaction starts from the electrophilic attack of carbene at the a-C atom of phosphorus ylide. Then the intermediately formed betaine (28) (Scheme 14) decomposes to eliminate the phosphine molecule and form dichloroolefin (29). 

A more general method for preparing carbenes often involves the a elimination of halides from carbanions.1-57 PAC can be used to examine the rates and energetics of the reverse reactions, the complexation of halides with carbenes (Fig. 5).58 Plots of A//com versus the proton affinities (PA) of the halides are linear for the two carbenes studied. Although the slopes of the plots are similar, complexation of the halides with phenylchlorocarbene is more exothermic than phenylfluorocarbene. This indicates that fluoro substitution stabilizes the carbene relative to the carbanion more than chloro substitution. The rate of complexation of carbenes with salts has also been examined by nanosecond absorption spectroscopy.59... 

Furans. Reaction of a,a-dimethoxy ketones with 1 affords a dihydrofuran (2) presumably via a carbene (a) that inserts intramolecularly into a C—H of an adjacent methoxy group. The reaction often results directly in a furan, since the elimination of methanol from 2 is facile. 

Few examples of the preparation of six-membered heteroaromatic compounds using Fischer-type carbene complexes have been reported [224,251,381]. One intriguing pyridine synthesis, reported by de Meijere, is sketched in Figure 2.35. In this sequence a (2-aminovinyl)carbene complex first rearranges to yield a complexed 1 -azadiene, which undergoes intermolecular Diels-Alder reaction with phenylacetylene. Elimination of ethanol from the initially formed adduct leads to the final pyridine. 

As would be expected from their electron-deficient nature, carbenes are highly reactive. Carbenes can be generated by a-elimination reactions. 

Azirines are also made by carbene addition to nitriles (89 — 90) and by thermal or photochemical (68JA2869) elimination of N2 from vinyl azides (e.g. 91 — 92). Vinyl azides are prepared by the Hassner reaction (68JOC2686, 71ACR9), where iodine azide is first added to an alkene and the resultant (3-iodoazide is dehydrohalogenated with base (Scheme 37) (86RTC456). 

These reactions are important in synthetic organic chemistry, because they lead to highly reactive chemical species called carbenes and nitrenes. A carbene has two unpaired electrons on a carbon atom, a nitrene has two unpaired electrons on a nitrogen atom. They are formed through the elimination of N2 from azo-compounds, RN2, and from azides, RN3 (Figure 4.34b). 

Iron(II) porphyrins react readily with haloalkanes in the presence of reducing agents, e.g., excess iron powder, to give chlorocarbene complexes 15,32). With the insecticide DDT [2,2-bis(4-chlorophenyl)-1,1,1 -trichloro-ethane, (C1C6H4)2CHCC13], the reaction proceeds one step further, by elimination of HC1 from the carbene complex, to give diarylvinylidene complexes 33) ... 

The three-component reaction of bis(phenylthio)-(trimethylsilyl)methyl lithium (243), phenyloxirane and a terminal alkene yields cyclopropanes 245142 (equation 82). It is assumed that a-elimination of LiSPh from the carbenoid-like species 243 generates phenylthio(trimethylsilyl)carbene (244) which is in equilibrium with 243 although this equilibrium is probably far on the side of the latter, trapping of the thiophenolate ion by the... 

Dehydroadamantanes are most readily obtained from either carbene insertion reactions or from 1,3-reductive eliminations. Pyrolysis of the dry sodium salt of the tosylhydrazone of adamantanone gives good yields of 2,4-dehydroada-mantane 133>. The unstable 1,3-dehydroadamantane is obtained from the treatment of 1,3-dibromoadamantane with sodium (Eq. (43)) 134>. 

Carbenes are formed in a number of other similar reactions—for example, loss of carbon monoxide from ketenes or elimination of nitrogen from azirines—but these are rarely used as a way of deliberately making carbenes. 

The observation by Fischer et al.18 that the 4,1-addition of dimethylamine to compound la is thermodynamically controlled at 20°C, whereas 2,1-addition/elimination is kinetically controlled at -115°C, turned out to be limited to few cases.20 It has been shown9a 9b 42 112 113 that for most cases, three competing reaction paths must be considered (i) 2,1-addition/elimina-tion with formation of (l-amino)alkynylcarbene complexes (= 2-amino-l-metalla-l-en-3-ynes) 98 (ii) 4,1-addition to give [(2-amino)alkenyl]carbene complexes (= 4-amino-l-metalla-l,3-butadienes) 96 and (iii) 4,1-addition/ elimination to (3-amino)allenylidene complexes (= 4-amino-l-metalla-1,2,3-butatrienes) 99 (Scheme 33, M = Cr, W). The product ratio 96 98 99 depends on the bulk of substituents R and R1, as well as on the reaction conditions. Addition of lithium amides instead of amines leads to predominant formation of allenylidene complexes 99.112 Furthermore, compounds 99 also can be generated by elimination of ethanol from complexes 96 with BF3 or AlEt3114 and A1C13,113 respectively. 

The oxidation state of the precursor ranges from W(0) to W(VI). but the oxidation state of the actual active site is very probably low. Tlie intriguing problem of the initial carbene formation has received acceptable explanations from Muetterties and Green s observations of a-elimination of hydrogen from W-CH) groups [9], Several reports of the formation of carbenoids by such reactions have been given in the literature (4.9). 

On the other hand, generation of free carbenes can be thermally achieved from C-protected NHC . In 1995, Enders reported the thermal elimination of methanol from 5-methoxy-l,3,4-triphenyl-4,5-dihydro-l//-l,2,4-triazole (12) affording the corresponding carbene l,2,4-triazol-5-ylidene (13) in quantitative yield (Scheme 2). Methanol adduct (12) is easily synthesized from reaction of triazolium perchlorate (11) and NaOCH3 in methanol. 

The Si-C bond is also broken in various elimination reactions. Thermally induced a elimination of RgSiX can occur either from saturated or unsaturated carbon to produce the corresponding carbene. 

In the Diels-Alder reaction, the typical dienophile will display lower stereoselectivity with acyclic dienes than with cyclic dienes. This is the case for the reactions of both methyl ciotonate and the prope-nyl tungsten complex (52b) with Danishefsky s diene (Scheme 9). Carbene complex (52b) gives a 58 42 selectivity in favor of the exo adduct (66), while methyl crotonate gives a similar selectivity of 66 34 in favor of the exo adduct (63) (64 and 65 are both derived from elimination of methanol from the endo adduct). This example reveals that the Diels-Alder reactions of caibene complexes are viable with functionalized and highly electron rich dienes. Furthermore, although the reaction of the carbene complex (52b) with Danishefsky s diene is not stereoselective, it does occur with a much greater rate and efficiency than that for the organic ester for which it can serve as synthon. 

As already mentioned for rhodium carbene complexes, proof of the existence of electrophilic metal carbenoids relies on indirect evidence, and insight into the nature of intermediates is obtained mostly through reactivity-selectivity relationships and/or comparison with stable Fischer-type metal carbene complexes. A particularly puzzling point is the relevance of metallacyclobutanes as intermediates in cyclopropane formation. The subject is still a matter of debate in the literature. Even if some metallacyclobutanes have been shown to yield cyclopropanes by reductive elimination [15], the intermediacy of metallacyclobutanes in carbene transfer reactions is in most cases borne out neither by direct observation nor by clear-cut mechanistic studies and such a reaction pathway is probably not a general one. Formation of a metallacyclobu-tane requires coordination both of the olefin and of the carbene to the metal center. In many cases, all available evidence points to direct reaction of the metal carbenes with alkenes without prior olefin coordination. Further, it has been proposed that, at least in the context of rhodium carbenoid insertions into C-H bonds, partial release of free carbenes from metal carbene complexes occurs [16]. Of course this does not exclude the possibility that metallacyclobutanes play a pivotal role in some catalyst systems, especially in copper-and palladium-catalyzed reactions. 

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