Transition Metal-Catalyzed Reactions of Carbenes

Carbene chemistry constitutes a particular but challenging field in organic synthesis. Carbenes offer a straightforward access to small rings (cyclopropanes, cyclopropenes) as well as to cycloheptatriene derivatives (the Buchner reaction) from cheap raw material (olefins, acetylenes, benzenic compounds, etc.). 

However, the selectivity of these processes is difficult to mediate, as may be expected from the high reactivity of carbenes in addition to the above reaction, they also lead to insertion reactions into OH, NH and even aliphatic CH bonds. Moreover, the formation of the formal dimerization and polymerization products of carbenes very often contributes to a decrease in the yield of the desired reaction products. 

Transition metal catalysis offers, in fact, a powerful means to mediate their reactivity and selectivity since the end of the last century, copper catalysis was largely applied in this context. More recently, the discovery of efficient catalysis by Group VIII complexes (particularly of rhodium(II) carboxylates, and (in some particular cases) of palladium(II) carboxylates)) now offers novel opportunities for preparative chemistry. 

Other promising applications of transition metals in carbene based synthesis result from stoichiometric reactions of particular carbene precursors such as  

However, we shall report here only some typical applications of these reactions (an exhaustive review of this interesting but speciahzed area of chemistry being outside the frame of the present publication). 

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Demonceau A, Noels AF, Hubert AJ (1988) Recent Aspects of Transition Metal Catalyzed Reactions of Carbenes in the Realm of Biologically Active Substances in Aspects Homogeneous Catalysis, edited by R. Ugo and D. Reibel, (Publ. Comp., Dordrecht), Vol. 6, pp. 199-232... 

RECENT ASPECTS OF TRANSITION METAL CATALYZED REACTIONS OF CARBENES IN THE REALM OF BIOLOGICALLY ACTIVE SUBSTANCES... 

Transition metal-catalyzed reactions of ct-diazocarbonyl compounds proceed via electrophilic Fischer-type carbene complexes. Consequently, when cr-diazoketone 341 was treated, at room temperature, with catalytic amounts of [ RhiOAcbh, it gave the formation of a single NH insertion product, which was assigned to the enol stmcture 342. At room temperature, in both solid state and in solution, 342 tautomerizes to give the expected 1-oxoperhydropyr-rolo[l,2-c]oxazole derivative 343 (Scheme 50) <1997TA2001>. 

The metal-carbene complexes postulated as intermediates in transition metal-catalyzed reactions of diazo compounds are electrophilic species (especially if they are derived from a-diazocarbonyl compounds). Accordingly, electron-rich olefins are the most suitable substrates for copper-catalyzed cyclopropanations, whereas electron-poor substrates such as a,P-unsaturated carbonyl compounds in general are not sufficiently reactive. 

Diazo compounds can be dediazonized by transition metal complexes to generate metallocarbenes, which are important intermediates in various transformations [45-48]. Since tosylhydrazones have been found to be readily available precursors of diazo compounds through the Bamford-Stevens reaction, a series of transition metal-catalyzed reactions of aldehyde tosylhydrazone salts in the presence of base and phase transfer catalyst (PTC) have been reported since 2000 [49-53]. It has been considered that metal carbenes generated from the in situ generated diazo compounds are involved in the catalytic cycle of these reactions -see (7). 

In the light of these results, it becomes important to question whether a particular catalytic result obtained in a transition metal-catalyzed reaction in an imidazolium ionic liquid is caused by a metal carbene complex formed in situ. The following simple experiments can help to verify this in more detail a) variation of ligands in the catalytic system, b) application of independently prepared, defined metal carbene complexes, and c) investigation of the reaction in pyridinium-based ionic liquids. If the reaction shows significant sensitivity to the use of different ligands, if the application of the independently prepared, defined metal-carbene complex... 

In most transition metal-catalyzed reactions, one of the carbene substituents is a carbonyl group, which further enhances the electrophilicity of the intermediate. There are two general mechanisms that can be considered for cyclopropane formation. One involves formation of a four-membered ring intermediate that incorporates the metal. The alternative represents an electrophilic attack giving a polar species that undergoes 1,3-bond formation. 

The common by-products obtained in the transition-metal catalyzed reactions are the formal carbene dimers, diethyl maleate and diethyl fumarate. In accordance with the assumption that they owe their formation to the competition of olefin and excess diazo ester for an intermediate metal carbene, they can be widely suppressed by keeping the actual concentration of diazo compound as low as possible. Usually, one attempts to verify this condition by slow addition of the diazo compound to an excess (usually five- to tenfold) of olefin. This means that the addition rate will be crucial for the yields of cyclopropanes and carbene dimers. For example, Rh6(CO)16-catalyzed cyclopropanation of -butyl vinyl ether with ethyl diazoacetate proceeds in 69% yield when EDA is added during 30 minutes, but it increases to 87 % for a 6 h period. For styrene, the same differences were observed 65). 

Metallocyclobutanes from cyclopropanes have been frequently invoked in transition metal-catalyzed rearrangements of strained ring hydrocarbons, and this body of chemistry is quite rich and diverse, as evidenced in the excellent review by Bishop (72). Because of this diversity, the significance of isolated observations should not be overstated nevertheless, certain reactions outlined by Bishop are closely related to the carbene retroadditions reported by Gassman and co-workers using metathesis catalysts. 

The transition metal-catalyzed cyclopropanation of alkenes is one of the most efficient methods for the preparation of cyclopropanes. In 1959 Dull and Abend reported [617] their finding that treatment of ketene diethylacetal with diazomethane in the presence of catalytic amounts of copper(I) bromide leads to the formation of cyclopropanone diethylacetal. The same year Wittig described the cyclopropanation of cyclohexene with diazomethane and zinc(II) iodide [494]. Since then many variations and improvements of this reaction have been reported. Today a large number of transition metal complexes are known which react with diazoalkanes or other carbene precursors to yield intermediates capable of cyclopropanating olefins (Figure 3.32). However, from the commonly used catalysts of this type (rhodium(II) or palladium(II) carboxylates, copper salts) no carbene complexes have yet been identified spectroscopically. 

Silanes can react with acceptor-substituted carbene complexes to yield products resulting from Si-H bond insertion [695,1168-1171]. This reaction has not, however, been extensively used in organic synthesis. Transition metal-catalyzed decomposition of the 2-diazo-2-phenylacetic ester of pantolactone (3-hydroxy-4,4-dimethyltetrahydro-2-furanone) in the presence of dimethyl(phenyl)silane leads to the a-silylester with 80% de (67% yield [991]). Similarly, vinyldiazoacetic esters of pantolactone react with silanes in the presence of rhodium(II) acetate to yield a-silylesters with up to 70% de [956]. 

The normal byproducts formed during the transition metal-catalyzed decomposition of diazoalkanes are carbene dimers and azines [496,1023,1329], These products result from the reaction of carbene complexes with the carbene precursor. Their formation can be suppressed by slow addition (e.g. with a syringe motor) of a dilute solution of the diazo compound to the mixture of substrate and catalyst. Carbene dimerization can, however, also be a synthetically useful process. If, e.g., diazoacetone is treated with 0.1% RuClCpIPPhjij at 65 °C in toluene, cw-3-hexene-2,5-dione is obtained in 81% yield with high stereoselectivity [1038]. 

Tejel C, Ciriano MA (2007) Catalysis and Organometallic Chemistry of Rhodium and Iridium in the Oxidation of Organic Substrates. 22 97-124 Tekavec TN, Louie J (2006) Transition Metal-Catalyzed Reactions Using N-Heterocyclic Carbene Ligands (Besides Pd- and Ru-Catalyzed Reactions). 21 159-192 Tesevic V, see Gladysz JA (2008) 23 67-89... 

This article presents the principles known so far for the synthesis of metal complexes containing stable carbenes, including the preparation of the relevant carbene precursors. The use of some of these compounds in transition-metal-catalyzed reactions is discussed mainly for ruthenium-catalyzed olefin metathesis and palladium-Znickel-catalyzed coupling reactions of aryl halides, but other reactions will be touched upon as well. Chapters about the properties of metal- carbene complexes, their applications in materials science and medicinal chemistry, and their role in bioinorganic chemistry round the survey off. The focus of this review is on ZV-heterocyclic carbenes, in the following abbreviated as NHC and NHCs, respectively. 

Reaction of diazo compounds with a variety of transition metal compounds leads to evolution of nitrogen and formation of products of the same general type as those formed by thermal and photochemical decomposition of diazoalkanes. These transition metal-catalyzed reactions in general appear to involve carbenoid intermediates in which the carbene becomes bound to the metal.83 The metals which have been used most frequently in synthesis are copper and rhodium. 

Oxa-l -silabicyclo[ . 1,0 alkanes (n = 3 111 n = 4 113) were the only products isolated from the photochemical, thermal or transition-metal catalyzed decomposition of (alkenyloxysilyl)diazoacetates 110 and 112, respectively (equation 28)62. The results indicate that intramolecular cyclopropanation is possible via both a carbene and a carbenoid pathway. The efficiency of this transformation depends on the particular system and on the mode of decomposition, but the copper triflate catalyzed reaction is always more efficient than the photochemical route. For the thermally induced cyclopropanation 112 —> 113, a two-step noncarbene pathway at the high reaction temperature appears as an alternative, namely intramolecular cycloaddition of the diazo dipole to the olefinic bond followed by extrusion of N2 from the pyrazoline intermediate. A direct hint to this reaction mode is the formation of 3-methoxycarbonyl-4-methyl-l-oxa-2-sila-3-cyclopentenes instead of cyclopropanes 111 in the thermolysis of 110. 

Abstract Major advances in transition-metal catalyzed reactions have taken place since the discovery of N-heterocydic carbenes (NHCs). This review provides a summery of recent M-NHC catalyzed reactions including cycloadditions, rearrangements, coupling reactions, polymerizations, and the additions of H-X. 

With the application of N-heterocyclic carbene (NHC) ligands, the number of transition metal-catalyzed reactions has grown considerably in the past decade. The replacement of traditional amine or phosphine ligands with electron-rich NHC ligands has led to a substantial enhancement in catalytic activity. This chapter summarizes the recent impact that the use of NHC ligands has had in furthering the field of transition metal-mediated catalysis. 

Fischer-type carbenes can also be modified via transition metal catalyzed reactions. Fischer chromium aminocarbene complexes can be used as nucleophiles in palladium-catalyzed allyUc substitution reactions with aUylic acetates and carbonates, alFording the corresponding allyl-substituted aminocarbenes. For example, reaction of the Uthiated carbene (15) gives (16) in good yield (Scheme 25). ... 

A transition metal catalyzed synthesis of ethers by carbene insertion into the O—bond has been reported. Not only saturated but also unsaturated alcohols can be utilized in this catalytic process. ° Intermolecular and intramolecular oxirane ring opening reactions by alkoxides and phenoxides also provide efficient and stereospecific preparations of acyclic and cyclic ethers. The procedures have been surveyed in detail. ... 

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