Formates free” carbenes

However, formation of the metal carbene complex was not observed in pure, halide-free [BMIM][Bp4], indicating that the formation of carbene depends on the... 

This group showed that isolable silver(I) diaminocarbene complexes can be use in situ instead of free carbenes, to generate the copper carbene complex. The silver salts that precipitates during the formation of the copper complex have not any negative effect on the conversion. This method is advantageous since most of the silver complexes are isolable, air-stable and easily obtained by treatment of the corresponding imidazohnium salt by 0.5 equiv of silver oxide (Scheme 53). The solid structure of 78 was analyzed by X-ray diffraction. 

Transition metal-catalyzed carbenoid transfer reactions, such as alkene cyclopro-panation, C-H insertion, X-H insertion (X = heteroatom), ylide formation, and cycloaddition, are powerful methods for the construction of C-C and C-heteroatom bonds [1-6]. In contrast to a free carbene, metallocarbene-mediated reactions often proceed stereo- and regioselectively under mild conditions with tolerance to a wide range of functionalities. The reactivity and selectivity of metallocarbenes can be... 

The most convenient tool for the characterisation of NHCs is NMR spectroscopy, in particular C H NMR. As a case study, the carbenes IPr and SIPr, and their corresponding salts IPr HCl and SIPr HCl were chosen. As described above (Scheme 1.2), free carbenes are often obtained by deprotonation of the corresponding salt. The best diagnostic tool to observe the salt deprotonation, and thus indirectly monitor the carbene formation, is H NMR spectroscopy, by means of the disappearance of the characteristic acidic proton resonance. The signal corresponding to the latter (ff) is largely shifted downfield (typically 8-12 ppm) and disappears upon deprotonation (Fig. 1.5). 

The carbene formation can be monitored by C H NMR, as the carbene carbon atom of free NHCs has a signal significantly shifted downfield. Typically, the signal for the O atom is found between 200 and 250 ppm for the free carbene and between 130 and 160 ppm for the corresponding salt... 

Based on this work, it has been proposed that a specifically solvated carbene (Scheme 4.6, Reaction 2) nndergoes bimolecular reactions at slower rates than a free carbene (Scheme 4.6, Reaction 1). Other alternatives that mnst be considered are participation of rapid and reversible ylide formation with the ylide acting as a... 

A Mechanism for Alkylidene Formation. There is no unambiguous example of free-carbene capture by a metal substrate, and the mild reaction conditions used in the generation of these carbene complexes from diazoalkanes suggests that such a mechanism is highly unlikely here. Transition metal diazoalkane complexes, then, are almost certainly implicated as intermediates in these reactions. 

Utilizing prochiral a,a-disubstituted Michael acceptors, the Stetter reaction catalyzed by 76a has proven to be both enantio- and diastereoselective, allowing control of the formation of contiguous stereocenters Eq. 8 [73]. It is noteworthy that a substantial increase in diastereoselectivity is observed, from 3 1 to 15 1, when HMDS, the conjugate acid formed upon pre-catalyst deprotonation, is removed from the reaction vessel. Reproducible results and comparable enantioselectivities are observed with free carbenes for example, free carbene 95 provides 94 in 15 1 diastereoselectivity. The reaction scope is quite general and tolerates both aromatic and aliphatic aldehydes (Table 9). 

The MCR toward 2//-2-imidazolines (65) has found apphcation in the construction of A(-heterocyclic carbene (NHC) complexes (74). Alkylation of the sp Af-atom with an alkyl halide followed by abstraction of the proton at C2 with a strong base (NaH, KOtBu) resulted in the formation of the free carbene species, which could be trapped and isolated as the corresponding metal complexes (Ir or Rh) [160]. The corresponding Ru-complexes were shown to be active and selective catalysts for the transfer hydrogenaticm of furfural to furfurol using iPrOH as hydrogen source [161]. 

The most generally employed approach for the formation of cyclopropanes is the addition of a carbene or carbenoid to an alkene. In many cases, a free carbene is not involved as an actual intermediate, but instead the net, overall transformation of an alkene to a cyclopropane corresponds, in at least a formal sense, to carbene addition. In turn, the most traditional method for effecting these reactions is to employ diazo compounds, R R2 —N2, as precursors. Thermal, photochemical and metal-catalyzed reactions of these diazo compounds have been studied thoroughly and are treated separately in the discussion below. These reactions have been subjects of several comprehensive reviews,8 to which the reader is referred for further details and literature citations. Emphasis in the present chapter is placed on recent examples. 

These carbene (or alkylidene) complexes are used as either stoichiometric reagents or catalysts for various transformations which are different from those of free carbenes. Reactions involving the carbene complexes of W, Mo, Cr, Re, Ru, Rh, Pd, Ti and Zr are known. Carbene complexes undergo the following transformations (i) alkene metathesis (ii) alkene cyclopropanation (iii) carbonyl alkenation (iv) insertion to C—H, N—H and O—H bonds (v) ylide formation and (vi) dimerization. Their chemoselectivity depends mainly on the metal species and ligands, as discussed in the following sections. 

Chavan and coworkers provide evidence that the Wolff rearrangement is facilitated by the formation of silver nanoclusters, which initiate electron transfer to the diazo compound providing 8. While the precise fate of this species remains to be firmly established, they suggest a multicycle process involving the intermediacy of a silver carbene 10 (Scheme 8.2).10 12 Decomposition of the silver carbene to the free carbene 14 precedes rearrangement to ketene 13, which is then trapped with water to provide the carboxylic acid 15 (Scheme 8.2). 

Although some carbenes are reported not to add to cyclopropenes207, there are several examples of inter- and intra-molecular addition leading initially to the formation of bicyclobutanes. l,2-Diphenylcyclopropene-3-carboxylates are converted to a mixture of three stereoisomeric bicyclo[1.1.0]butanes by reaction with ethoxy-carbonylcarbene generated from the thermolysis of ethyl diazoacetate an additional product is the diene (278) which is apparently formed by rearrangement of an intermediate zwitter ion208). It should be noted, however, that cyclopropenes readily undergo addition to diazo-compounds, and that subsequent transformations may then lead to bicyclobutanes (see Section 8), and that a free carbene may therefore not be involved in the above process. 

The formation of five- and six-membered heterocycles by radical cyclization is discussed in a comprehensive review <2004H(63)1903>. Representative examples of ring syntheses involving carbenoid (Table 6) or nitrenoid (Table 7) intermediates are given. In many cases, the free carbene or nitrene is probably not involved, and the distinction between insertion and addition reactions given in the tables is not always clear cut. Such reactions are particularly useful for the preparation of tricyclic compounds. The application of carbenes and carbenoids in the synthesis of heterocyles is summarized in a review <1996AHC(65)93>. 

The complications that occasionally arise in the use of diazoalkanes reflect the possible further reactions of carbene ligands, which will be dealt with subsequently, e.g. insertion into adjacent M-H or M-halide bonds and the formation of bimetallic complexes supported by bridging carbene ligands. In some cases, transition metals may catalyse reactions of diazoalkanes, leading to products which are suggestive of the reactions of free carbenes, i.e. dimerization, addition to alkenes (cyclo-propanation) and insertion into C-H bonds (Figure 5.9). In such cases, however, the actual mechanism does not involve free carbenes but rather transient diazoalkane/carbene complexes. This is supported by the obser-... 

In consideration of conceivable strategies for the more direct construction of these derivatives, nitriles can be regarded as simple starting materials with which the 3+2 cycloaddition of acylcarbenes would, in a formal sense, provide the desired oxazoles. Oxazoles, in fact, have previously been obtained by the reaction of diazocarbonyl compounds with nitriles through the use of boron trifluoride etherate as a Lewis acid promoter. Other methods for attaining oxazoles involve thermal, photochemical, or metal-catalyzed conditions.12 Several recent studies have indicated that many types of rhodium-catalyzed reactions of diazocarbonyl compounds proceed via formation of electrophilic rhodium carbene complexes as key intermediates rather than free carbenes or other types of reactive intermediates.13 If this postulate holds for the reactions described here, then the mechanism outlined in Scheme 2 may be proposed, in which the carbene complex 3 and the adduct 4 are formed as intermediates.14... 

An elegant method to generate the free carbene is the reaction of the imidazoUum salt precursor with sodium hydride in liquid ammonia. In contrast to other solvents, liquid ammonia dissolves both, the imidazolinm salt and the base (NaH) providing a medium for smooth, efficient deprotonation and carbene formation in high yields [57,58] (see Figure 1.8). 

Phosphino functionalised carbenes do not need to be used in situ or the carbene complexes generated without the formation of the free carbene. Danopoulos et al. have isolated and structurally characterised a phosphino functionahsed carbene after deprotonation of the corresponding imidazoUum salt with KNfSiMej) [280], a feat repeated by Hodgson and Douthwaite using a chiral imidazolium salt [243]. 

The more popular routes towards transition metal phosphino functionalised carbene complexes avoid the formation of the free carbene and apply one of several in situ methods. Lee et al. reacted the phosphino functionalised imidazolium salt with palladium(II) chloride in the presence of sodium acetate as base [241,281] resulting in the expected paUadium(II) chelate complex. 

The next challenge encountered was the formation of the free carbene ligand which failed irrespective of the base and reaction conditions. In each case decomposition of the azolium salt was the only result. A similar observation was made for certain electron deficient annulated... 

Asymmetric copper catalysts arc less efficient. Low optica) yields were obtained with chiral phosphine liijpinds, and these experimems wctc significant in proving the formation of copper carbenoids rather than free carbenes in the copper catalyzed decomposition of diaio compounds. From a practical point of view, however, the optical yield was too low to be of much interest. The best results with copper catalysts were those obtained by Aratani [36] using complex (36). 

The availability of free carbene as a reagent prompted the development of TM complexes bearing these NHC ligands. Their formation can be achieved using various... 

Treatment oftheRu hydride [RuHCl(CO)(PCy3)] (67) with a free carbene such as IMes proceeds by the easy and selective phosphine displacement and formation of complex (68) (equation 8). At the time of this article, this synthetic pathway has been extended to analogs [(IPr)RuHCl(PCy3)], [(IMes)RuHCl(PPh3)], and [(SIMes)RuHCl (PPh3)]... 

In conclusion, we have shown that the mercury way is another route to generate amino carbenes. In the case of diaminocarbenes, this synthetic approach provides us with metal-free carbenes, which are usually not accessible by the deprotonation procedure. The fact that we never observed the formation of dimers in our experiments with diaminocarbenes showed that metal cations are also of importance for the dimerization. 

Of the three classes of divalent carbon species—free carbenes, reactive transition-metal carbene complexes (carbenoids), and stable metal carbenes—we restrict our consideration to the first two. Taking into account the fact that a fine reaction mechanism in planning the synthesis of specific molecules is of secondary importance, we discuss carbene and carbenoid reactions together. We concentrate solely on reactions and reaction sequences that result in a formation of a new heterocycle. Within subsections, the material is organized on the basis of reaction type. 

The formation of free carbene 425 was postulated in the reaction of sulfides 426 with methyllithium. It is stabilized via cyclization into a four-membered sulfonium ylide 427, followed by rearrangement with ring expansion into thiabicyclo[3.1.0]hexane 428, which is isolated as a mixture of endo (72%) and exo (28%) isomers in an overall yield of 17-38%. However, simultaneous occurrence of side processes makes this reaction synthetically inappropriate [82ACS(B)593],... 

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. 

Although transition metal complexes do not usually react directly with free carbenes (with the exception of the formation of NHC-metal complexes, Section 10-2-3), low-valent Group 7 to 9 metal complexes in particular react with diazoalkanes to produce alkylidenes. Equation 10.17 shows a general example of this reaction. The complex must either be unsaturated or possess a labile L-type ligand so that the reaction can occur. The intermediate in this reaction is unlikely to be a free carbene. 

Another cyclopropanation procedure that is quite general involves the use of Rh-carbene complexes, which can act catalytically to effect ring formation. Scheme 10.7 shows some of the details of this method. Ccaibene is derived from corresponding diazo compounds, which were traditionally used directly as sources of free carbenes. The scheme includes a catalytic cycle for conversion of the diazo compound to the Rh-carbene complex, which then delivers Ccarbene to the alkene. Transfer of Ccaibene regenerates an active catalyst that can react with another mole of diazo compound. The detailed mechanism of step c in the cycle resembles path b from Scheme 10.6. 

Cyclopropane formation is achieved to a much larger extent when the dianion of cycloocta-tetraene is allowed to react with dichlorodiphenylmethane. It is doubtful that the reaction involves a free carbene, but in any case 9,9-diphenylbicyclo[6.1.0]nona-2,4,6-triene (2) was obtained in 51 % yield together with tetraphenylethene, isolated in 21 % yield, when the reaction was carried out in a diethyl ether/tetrahydrofuran solution at 0°C. ... 

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