From metal carbenoids

Using a Cu(n)-catalyzed reaction of 2-(4-diazo-3-oxoalkyl)pyridines 225, tetrahydroquinolizinium ylides 226 were obtained in high yields. This transition metal-catalyzed decomposition was found to be superior to that promoted by 

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Diazomethane is also decomposed by N O)40 -43 and Pd(0) complexes43 . Electron-poor alkenes such as methyl acrylate are cyclopropanated efficiently with Ni(0) catalysts, whereas with Pd(0) yields were much lower (Scheme 1)43). Cyclopropanes derived from styrene, cyclohexene or 1-hexene were formed only in trace yields. In the uncatalyzed reaction between diazomethane and methyl acrylate, methyl 2-pyrazoline-3-carboxylate and methyl crotonate are formed competitively, but the yield of the latter can be largely reduced by adding an appropriate amount of catalyst. It has been verified that cyclopropane formation does not result from metal-catalyzed ring contraction of the 2-pyrazoline, Instead, a nickel(0)-carbene complex is assumed to be involved in the direct cyclopropanation of the olefin. The preference of such an intermediate for an electron-poor alkene is in agreement with the view that nickel carbenoids are nucleophilic 44). 

It has been widely accepted that the carbene-transfer reaction using a diazo compound and a transition metal complex proceeds via the corresponding metal carbenoid species. Nishiyama et al. characterized spectroscopically the structure of the carbenoid intermediate that underwent the desired cyclopropanation with high enantio- and diastereoselectivity, derived from (91).254,255 They also isolated a stable dicarbonylcarbene complex and demonstrated by X-ray analysis that the carbene moiety of the complex was almost parallel in the Cl—Ru—Cl plane and perpendicular to the pybox plane (vide infra).255 These results suggest that the rate-determining step of metal-catalyzed cyclopropanation is not carbenoid formation, but the carbene-transfer reaction.254... 

The metal-carbenoid intermediates, especially ones derived from a-diazocarbonyl compounds, are electrophilic, and electron-rich olefins in general react more easily with the carbenoid intermediates than electron-deficient olefins. For the interaction of metal carbenoid and olefin, three different mechanisms have been proposed, based on the stereochemistry of the reactions and the reactivity of the substrates (Figure 12) 21 (i) a nonconcerted, two-step process via a metallacyclobutane 226,264... 

The electrophilic reactivity of lithium carbenoids (reaction b) becomes evident from their reaction with alkyl lithium compounds. A, probably metal-supported, nucleophilic substitution occurs, and the leaving group X is replaced by the alkyl group R with inversion of the configuration . This reaction, typical of metal carbenoids, is not restricted to the vinylidene substitution pattern, but occurs in alkyl and cycloalkyl lithium carbenoids as well ". With respect to the a-heteroatom X, the carbenoid character is... 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

A promising synthetic transformation is the reaction of carbenoid intermediates with heteroatoms to form ylides that are capable of undergoing further transformations [5,6]. Enantioselective transformations in which the ylide intermediates undergo either 1,2- or 2,3-sigmatropic rearrangement were briefly reviewed in the previous issue (Vol. II, pp. 531-532) and several recent examples have appeared [37]. A major breakthrough has been made in the enantioselective transformation of carbonyl ylides derived from capture of the metal carbenoid intermediates by carbonyl groups. The carbonyl ylides have been ex-... 

The Tebbe Reagent is a metal carbenoid prepared from the dimetallomethylene species derived by the reaction of trimethyl aluminium with titanocene dichloride this reagent exhibits carbenoid behaviour after the addition of a catalytic amount of pyridine. The Tebbe Reagent reacts with various carbonyl partners to give the product of methylenation ... 

Intramolecular insertions of metal carbenoids from diazo compounds... 

Since the observation that Rh(II) carboxylates are superior catalysts for the generation of transient electrophilic metal carbenoids from a-diazocar-bonyls compounds, intramolecular carbenoid insertion reactions have assumed strategic importance for C-C bond construction in organic synthesis [1]. Rhodium(ll) compounds catalyze the remote functionalization of carbon-hydrogen bonds to form carbon-carbon bonds with good yield and selectivity. These reactions have been particularly useful in the intramolecular sense to produce preferentially five-membered rings. 

Examples of alkane functionalization reactions of the type shown in equation (1) are first considered, in which the atom X to which the new C—X bond is form comes from metals in Group I, followed by subsequent groups in the Periodic Table. Within each section, radical, electrophilic and carbenoid mechanisms are (Uscussed. 

The formation of transition metal carbenoids originates from dilTcrem possible pathways ... 

Dihydrofuran derivatives 319 are formed as major products in Rh2(OAc)4-catalyzed reactions of a-diazoacetophenone with 2-methoxy-propene or a-methoxystyrene (84MI1). Copper chelate or rhodium(II) acetate-catalyzed 1,3-dipolar cycloaddition of metal carbenoids, generated from ethyl formyldiazoacetate (90JOC4975), ethyl diazopyruvate... 

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. 

Development of chiral transition-metal catalysts enables one to perform the catalytic C—H insertion to metal carbenoids, generated from diazo compounds, in an enantioselective manner. Davies et al. reported that the asymmetric intramolecular reaction of the aryldiazoacetates 684 in the presence of Rh2-(S-DOSP)4 gave the C-H insertion products 685 (Scheme 212). 288b The enantioselectivity is strongly dependent on the site of the C-H activation the highest enantioselectivity was obtained for insertion into the methyne C—H bond. 

Carbenoid insertion. The Ru complex is also effective in forming metal-carbenoids from diazoalkanes for insertion into X—H bonds, as exemplified by the formation of pioline... 

Formation of cyclopropanecarboxylic esters by capture of the metal-carbenoid derived from diazoacetates with alkenes is rendered enantioselective by a chiral 2,2 -bipyridine (2) [complexed to Cu] and a bis(oxazolinyl)pyridine (2a) [complexed to Ru]. ... 

Furans may be formed in the reaction with metal carbenoids derived from diazocarbonyl compounds, if alkynes are used instead of alkenes. Furan formation is particularly favored when the carbenoid is a 3-diazo-2-oxopropionate (e. g., 8.110, Wenkert et al., 1983) or contains two electron-withdrawing groups (see Davies and Romines, 1988) and when electron-donating groups are present in the alkyne. Davies... 

Rhodium (II) catalyzed 1,3-dipolar reactions of metal carbenoid 30 (derived from diazocompound 31) leads to the formation of 2-peifluoroaIkylfurans 32." ... 

On the other hand, the dirhodium bridge caged within a lantern structure is thought to be essential to the success of dirhodium complexes in which two rhodium atoms are surrounded by four ligands in a nominal symmetry. Both computational studies and characterization of dirhodium car-benoid intermediates suggested that the intermediate adopts a Rh—Rh=C framework. In another word, two rhodium atoms are bound to one carbene center, and the bonding scenario obeys the three-center orbital paradigm. As such, metal carbenoids derived from chiral Rh complexes and donor/ acceptor diazo compounds are routinely utilized. 

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