Synthesis of Metal Carbene Complexes

There are numerous synthetic routes to Fischer carbene complexes.21 We may classify these routes as fundamentally of two kinds  

In this section, our discussion focuses on the type A pathway. Because modification of an existing carbene ligand to produce a new carbene is an example of a type of reaction carbenes may undergo, we will postpone discussion of type B reactions until Section 10-3. 

Following are a few general methods for the preparation of Fischer-type carbene complexes. 

Formation of Carbene Complexes by Nucleophilic Attack at a Carbonyl Ligand 

Equation 10.6 shows the original work of Fischer and Maasbol in preparing the first reported metal-carbene complex. Attack by the carbanion (see equation 8.28 

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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. 

Many of the recent efforts in this area of chemistry have been designed to explore the chemistry of the trifluoromethyl species prepared by these reactions. Among the more interesting results have been the construction of carbene and tetramethylcyclobutadiene ligands affixed to trifluoromethyl platinum cations (78), the synthesis of difluoro-carbene complexes like (Cp)Mo(CO)3CF2+ (79), the formation of (CF3)2CS from CF3Re(CO)5 (38), and the insertion reaction of S02 into CF3-metal bonds (80). 

There is one exception to this statement. One route to the synthesis of AMieterocyclic carbene complexes involves complexation of the free carbene with a metal salt. Such complexes will be discussed later in this section. 

Because free NHCs bind so strongly to a metal, it is not necessary to use an excess amount of these ligands to make NHC-metal complexes. This contrasts with the synthesis of metal phosphine complexes, where often an excess of the ligand is required for success. There are numerous examples of simple combination of the free carbene and a suitable metal complex. Equation 10.25 illustrates one example.43... 

Chiral catalysts with heterocyclic ligands and asymmetric synthesis of heterocycles with participation of metal carbene complexes 01JOM(617-618)98. 

Various elementary processes such as oxidative addition, reductive elimination, olefin and CO insertion into the metal-to-carbon bond have found extensive applications in organic synthesis. Other processes such as attack of nucleophiles on metal-bound CO and olefins, unique reactions of metal carbene complexes, and a-bond metatheses are among the topics of special interest to organometalhc chemists as well as to synthetic organic chemists. Our aim is to provide the reader with detailed accounts of elementary processes with the hope that the information provided here is used for further development of molecular catalysis. 

IV. Application of Metal-Carbene Complexes in Organic Synthesis.. 228... 

In addition to the syntheses of metal-carbene complexes from compounds not containing the carbene ligand, a variety of methods for modifying the structure of carbene complexes have been developed. Three different reactive centers in a transition metal-carbene complex can be utilized in designing a synthesis of a new carbene complex (see Scheme 4). For example, (CO)s-CrC(OCH3)CH3 can be converted into a wide range of carbene complexes by (a) nucleophilic attack at the carbene carbon atom followed by loss of... 

The ligand substitution reactions of carbene complexes such as (CO)s-CrC(OCH3)CHj allow the synthesis of many phosphine- and phosphite-substituted carbene complexes. It is expected that these complexes will have modified reactivity and will provide a means of fine tuning reactions of carbene complexes. More importantly, the substitution reactions of carbene complexes proceed by a dissociative mechanism involving coordinatively unsaturated intermediates. Study of the ligand substitution reactions can give valuable information about these coordinatively unsaturated intermediates which are also involved in the important cyclopropanation, alkene scission, and thermolysis reactions of metal-carbene complexes. 

The ultimate utility of metal-carbene complexes in organic synthesis hinges on the discovery of synthetically useful ways of releasing the carbene ligand from its metal complexes. Several useful means of releasing the carbene... 

VI. APPLICATION OF METAL-CARBENE COMPLEXES IN ORGANIC SYNTHESIS... 

The rich and varied chemistry of metal-carbene complexes outlined in this chapter should eventually lead to the wide use of metal-carbene complexes in organic synthesis. To date, carbene complexes have not been used extensively as their chemistry was not widely understood and the reagents are moderately expensive. However, the applications of metal-carbene complexes in peptide synthesis, in the synthesis of an indole alkaloid, and in the synthesis of a-methylenebutyrolactone have been reported. These applications indicate some of the ways in which metal-carbene complexes may prove useful in synthesis. 

The use of metal-carbene complexes as an amino-protecting group in peptide synthesis has been reported by Fischer and Weiss (1973). The free amino group of an amino acid ester readily displaces the alkoxy group of an alkoxy-substituted carbene complex. The nitrogen atom of the resulting N-substituted carbene complex is nonbasic and nonnucleophilic because it bears a partial positive charge. The low reactivity of the amino-substituted carbene complex allows a series of reactions to be carried out to construct a peptide chain. Finally, the completed peptide chain can be removed from the carbene complex by treatment with trifluoroacetic acid at 20°. Scheme 16 illustrates the variety of reactions that can be carried out in the presence of the metal-carbene functionality. 

The conversion of an aminocarbene complex to an imine has been used to synthesize tetrahydroharman (XXIX) (Connor and Rose, 1972). This synthesis illustrates the use of metal-carbene complexes in the synthesis of complex organic structures. 

In Volume I, the versatility of olefin complexes in organic synthesis is amply demonstrated in Chapter 1 by Birch and Jenkins. Noyori has summarized the extensive work on coupling reactions of allyl complexes. In the final chapter of Volume 1, Casey considers both achievements and possible areas of use of metal-carbene complexes. 

These complexes, synthesized by E.O. Fischer in 1964, form a category called Fischer carbenes. They were the first successful approach to the synthesis and stabilization of metal-carbene complexes. They gave a rich chemistry (see Part V) because of their stability and ease of access. The presence of carbonyl ligands on the metal and of electronegative heteroatoms on the carbenic carbon makes this type of carbene electrophilic. i ... 

Complexes of nucleophilic carbenes are expected to react, like ylids, with electrophiles whereas complexes of electrophilic carbenes are expected to react, like carbocations, with nucleophiles and bases. All the complexes of terminal carbenes have in common the reactions with olefins, although their nature also varies. The principles of these reactions are detailed here, and application in catalysis and organic synthesis, are exposed in Parts IV and V respectively. Reactions of metal-carbene complexes leading to metal-carbyne complexes are mentioned in section 2. 

The reactions of metal-carbene complexes with olefins are important in catalysis and organic synthesis. The first reaction disclosed by Pettit in 1966 involved transient [FeCp(CO)2(=CH2)] that reacted with styrene to give phenylcyclopropane resulting from methylene transfer from the metallacarbocation to the olefin, a reaction that was shown later to be general with iron-methylene complexes of this series. ... 

In the same way, the reactions of metal carbene complexes with alkynes give metallacyclobutenes, which leads to applications in organic synthesis. Tebbe s methylene complex is in equilibrium with the metallacyclobutane by... 

A few years later, Tebbe and co-workers found that the methylene-bridged metallacycle 3, which has become known as the Tebbe reagent, is useful for the methylenation of ketones and aldehydes [5]. Titanocene-methylidene 4, the active species of this olefination, also transforms carboxylic acid derivatives into heteroatom-substituted olefins. Because the carbene complex 4 is much less basic than conventional olefination reagents such as phosphorus ylides, it can be employed for the olefination of carbonyl compounds possessing highly acidic a-protons or of highly hindered ketones, and has become an indispensable tool in organic synthesis. Various methods for the preparation of titaniumcarbonyl olefination. This chapter focuses on the use of metal-carbene complexes and some related species in carbonyl olefination (Scheme 4.2). 

As shown above, dianions 6O2 and 7Li2 appeared ideal for the synthesis of U carbene complexes of various oxidation states (IV, V, and VI), yet not for the stabilization of U(III) carbene (as of today). It is to be noted that this stabilization of different oxidation states by these kinds of ligands has not been observed so far for any other metal center. The nature of the interaction between the carbon center and the U center was therefore of high importance. This characterization was done by different experimental techniques (X-ray, UVWis/NIR, magnetism) as well as by DFT calculations. The U=C bond distances vary to a great extent in the reported complexes. 

A decade after Fischer s synthesis of [(CO)5W=C(CH3)(OCH3)] the first example of another class of transition metal carbene complexes was introduced by Schrock, which subsequently have been named after him. His synthesis of [((CH3)3CCH2)3Ta=CHC(CH3)3] [11] was described above and unlike the Fischer-type carbenes it did not have a stabilizing substituent at the carbene ligand, which leads to a completely different behaviour of these complexes compared to the Fischer-type complexes. While the reactions of Fischer-type carbenes can be described as electrophilic, Schrock-type carbene complexes (or transition metal alkylidenes) show nucleophilicity. Also the oxidation state of the metal is generally different, as Schrock-type carbene complexes usually consist of a transition metal in a high oxidation state. 

The potential of Fischer carbene complexes in the construction of complex structures from simple starting materials is nicely reflected in the next example. Thus, the reaction of alkenylcarbene complexes of chromium and tungsten with cyclopentanone and cyclohexanone enamines allows the di-astereo- and enantioselective synthesis of functionalised bicyclo[3.2.1]octane and bicyclo[3.3.1]nonane derivatives [12] (Scheme 44). The mechanism of this transformation is initiated by a 1,4-addition of the C -enamine to the alkenylcarbene complex. Further 1,2-addition of the of the newly formed enamine to the carbene carbon leads to a metalate intermediate which can... 

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