Carbene complexes Fischer-type

Fischer-type carbene complexes in the synthesis of furan, pyrrole, 5//-furanone, and 5//-pyrrolone derivatives 98YGK413. 

The surprising stability of N-heterocyclic carbenes was of interest to organometallic chemists who started to explore the metal complexes of these new ligands. The first examples of this class had been synthesized as early as 1968 by Wanzlick [9] and Ofele [10], only 4 years after the first Fischer-type carbene complex was synthesized [2,3] and 6 years before the first report of a Schrock-type carbene complex [11]. Once the N-heterocyclic ligands are attached to a metal they show a completely different reaction pattern compared to the electrophilic Fischer- and nucleophilic Schrock-type carbene complexes. 

Scheme 4 Schrock-type and Fischer-type carbene complexes...

Scheme 5 Synthesis of the first Fischer-type carbene complex...

Fischer-type carbene complexes, generally characterized by the formula (CO)5M=C(X)R (M=Cr, Mo, W X=7r-donor substitutent, R=alkyl, aryl or unsaturated alkenyl and alkynyl), have been known now for about 40 years. They have been widely used in synthetic reactions [37,51-58] and show a very good reactivity especially in cycloaddition reactions [59-64]. As described above, Fischer-type carbene complexes are characterized by a formal metal-carbon double bond to a low-valent transition metal which is usually stabilized by 7r-acceptor substituents such as CO, PPh3 or Cp. The electronic structure of the metal-carbene bond is of great interest because it determines the reactivity of the complex [65-68]. Several theoretical studies have addressed this problem by means of semiempirical [69-73], Hartree-Fock (HF) [74-79] and post-HF [80-83] calculations and lately also by density functional theory (DFT) calculations [67, 84-94]. Often these studies also compared Fischer-type and... 

The kinetic and thermodynamic properties of Fischer-type carbene complexes have also been addressed by Bernasconi, who relates the strength of the 7r-donor substituent to the thermodynamic acidity [95-101] and the kinetics and mechanism of hydrolysis and reversible cyclization to differences in the ligand X [96,102]. 

Fig. 1 A,B Dominant orbital interactions in Fischer-type carbene complexes (A) and Schrock-type carbene complexes (B)...

Anionic alkoxy Fischer-type carbene complexes were shown to react with (Ph3P)AuGl to give a unique vinyl ether complex, which is bound in a quasi-771 fashion to the Cr/Mo centers. Upon treatment with triphenylphosphine, the gold-vinyl ether ligand can be liberated and isolated. This reaction thus gives access for the first time to aurated vinyl ethers (Scheme 57).38... 

E.O. Fischer s discovery of (CO)sW[C(Ph)(OMe)D in 1964 marks the beginning of the development of the chemistry of metal-carbon double bonds (1). At about this same time the olefin metathesis reaction was discovered (2), but It was not until about five years later that Chauvln proposed (3) that the catalyst contained an alkylidene ligand and that the mechanism consisted of the random reversible formation of all possible metallacyclobutane rings. Yet low oxidation state Fischer-type carbene complexes were found not to be catalysts for the metathesis of simple olefins. It is now... 

Molybdenum dinitrosyl complexes with the general formula Mo(NO)2(CHR) (0R )2(A1C12)2 have been found to be active in a variety of metathesis reactions [110]. New alkylidenes could be identified. Variations such as Mo(NO)2(CHMe) (RC02)2 also are known [111]. Complexes of this type are believed to be more reduced than typical d° species discussed here, although they appear to be much more active as metathesis catalysts than typical Fischer-type carbene complexes. 

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>. 

Metallic groups as in case (c) lead to electrophilic or even carbocation-like carbene complexes. Typical examples are Fischer-type carbene complexes [e.g. (CO)5Cr=C(Ph)OMe] and the highly reactive carbene complexes resulting from the reaction of rhodium(II) and palladium(II) carboxylates with diazoalkanes. Also platinum ylides [1,2], resulting from the reaction of diazoalkanes with platinum(Il) complexes, have a strong Pt-C o bond but only a weak Pt-C 7t bond. In situation (d) the interaction between the metal and the carbene is very weak, and highly reactive complexes showing carbene-like behavior result. Similar to uncomplexed carbenes. 

Fischer-type carbene complexes, on the other hand, have a metallic group L M with d orbitals of lower energy than the group H4Ta- . This leads to a lower-lying 7t orbital, more susceptible to nucleophilic attack, and to a weaker M-C n bond [3,18]. 

The decisive difference between, e.g., [Cp(CO)2Fe]" and H4Ta- is the smaller amount of orbital overlap of the former with the carbene 2 p orbital, resulting in less efficient transfer of electron density from the metal to C . Although Fischer-type carbene complexes are formally low valent, backbonding to the carbene is less effective than in tantalum alkylidene complexes. 

The molybdenum complex 1, a typical high-valent Schrock-type carbene, efficiently catalyzes the self-metathesis of styrene. On the other hand, the cationic iron complex 3 does not induce metathesis but stoichiometrically cyclopropanates styrene. The tungsten complex 2, again a Fischer-type carbene complex, mediates... 

Calculations [28] on the formation of cyclopropanes from electrophilic Fischer-type carbene complexes and alkenes suggest that this reaction does not generally proceed via metallacyclobutane intermediates. The least-energy pathway for this process starts with electrophilic addition of the carbene carbon atom to the alkene (Figure 1.9). Ring closure occurs by electrophilic attack of the second carbon atom... 

Particularly stable are coordinatively saturated, 18-electron carbene complexes of the type (CO)5M=C(X)R (M W, Cr X OR, NR2 R H, alkyl, aryl). These complexes are often referred to as Fischer-type carbene complexes, in honor of E. O. Fischer, who prepared these compounds for the first time in 1964 [61]. Since then these compounds have attracted broad interest, and many hundreds of heteroatom-substituted carbene complexes have been synthesized. Thereby valuable new insights were gained into the nature of the carbon-metal double bond. These complexes are also becoming increasingly important for organic synthesis, both as reagents and as catalysts. 

Electrophilic vinylidene complexes, capable of reacting with non-carbon nucleophiles to yield Fischer-type carbene complexes, can be obtained by addition of electrophiles to alkynyl complexes (Figure 2.11, Table 2.7, Entries 11, 12) [134,144]. 

The reaction of alkoxy(aryl)carbene iron complexes with two equivalents of an isonitrile leads to the formation of azetidin-2-ylidene complexes [197]. For other reactions of Fischer-type carbene complexes with isonitriles see [198]. 

Heteroatom-substituted (Fischer-type) carbene complexes are mostly used as stoichiometric reagents. For this reason only carbene complexes of reasonably cheap metals, such as chromium, molybdenum, tungsten, or iron have found broad application in organic synthesis. 

As in carboxylic esters it is possible to substitute alkoxy groups of Fischer-type carbene complexes by non-carbon nucleophiles, such as other alcohols [73,214,218], enols [219], aliphatic amines [43,64,66,220-224], aniline [79], imines [225], or pyrroles [226]. Strong nucleophiles can also lead to a dealkylation of methoxy-substituted carbene complexes (5 2 at the methyl group, [227]), in the same way as methyl esters can be cleaved by nucleophiles such as iodide. Carbon... 

In addition to reactions characteristic of carbonyl compounds, Fischer-type carbene complexes undergo a series of transformations which are unique to this class of compounds. These include olefin metathesis [206,265-267] (for the use as metathesis catalysts, see Section 3.2.5.3), alkyne insertion, benzannulation and other types of cyclization reaction. Generally, in most of these reactions electron-rich substrates (e.g. ynamines, enol ethers) react more readily than electron-poor compounds. Because many preparations with this type of complex take place under mild conditions, Fischer-type carbene complexes are being increasingly used for the synthesis [268-272] and modification [103,140,148,273] of sensitive natural products. 

Treatment of Fischer-type carbene complexes with different oxidants can lead to the formation of carbonyl compounds [150,253]. Treatment with sulfur leads to the formation of complexed thiocarbonyl compounds [141]. Conversion of the carbene carbon atom into a methylene or acetal group can be achieved by treatment with reducing agents. Treatment of vinylcarbene complexes with diborane can also lead to demetallation and formation of diols [278]. The conversion of heteroatom-substituted carbene complexes to non-heteroatom-substituted carbene complexes... 

Fig. 2.19. Typical reactions of Fischer-type carbene complexes with carbanions and ylides.

Heteroatom-substituted carbene complexes are less electrophilic than the corresponding methylene, dialkylcarbene, or diarylcarbene complexes. For this reason cyclopropanation of electron-rich alkenes with the former does not proceed as readily as with the latter. Usually high reaction temperatures are necessary, with radical scavengers being used to supress side-reactions (Table 2.16). Also acceptor-substituted alkenes can be cyclopropanated by Fischer-type carbene complexes, but with this type of substrate also heating is generally required. 

Several reaction sequences have been reported in which Fischer-type carbene complexes are converted in situ into non-heteroatom-substituted carbene complexes, which then cyclopropanate simple olefins [306,307] (Figure 2.22). This can, for instance, be achieved by treating the carbene complexes with dihydropyridines, forming (isolable) pyridinium ylides. These decompose thermally to yield pyridine and highly electrophilic, non-heteroatom-substituted carbene complexes (Figure 2.22) [46]. 

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

The reaction of enynes with Fischer-type carbene complexes can also lead to the formation of cyclobutanones (Figure 2.23) [315]. The mechanism for this reaction is likely to be rearrangement of the intermediate, non-heteroatom-substituted vinylcarbene complex to a vinylketene, which undergoes intramolecular [2 -i- 2] cycloaddition to form the observed cyclobutanones. 

In addition to the reaction of vinylcarbene complexes with alkynes, further synthetic procedures have been developed in which Fischer-type carbene complexes are used for the preparation of benzenes. Most of these transformations are likely to be mechanistically related to the Dbtz benzannulation reaction, and can be rationalized as sequences of alkyne-insertions, CO-insertions, and electrocycli-zations. A selection of examples is given in Table 2.18. Entry 4 in Table 2.18 is an example of the Diels-Alder reaction (with inverse electron demand) of an enamine with a pyran-2-ylidene complex (see also Section 2.2.7 and Figure 2.36). In this example the adduct initially formed eliminates both chromium hexacarbonyl ([4 -I- 2] cycloreversion) and pyrrolidine to yield a substituted benzene. 

The reaction of alkoxy(alkyl)carbene chromium complexes with alkynes has been reported to give modest yields of cyclopentenones [368] and a few examples of intramolecular carbene C-H insertions of Fischer-type carbene complexes, leading to five-membered heterocycles, have been reported [369,370] (Table 2.22). 

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. 

Non-heteroatom-substituted vinylcarbene complexes are readily available from alkynes and Fischer-type carbene complexes. These intermediates can undergo the inter- or intramolecular cyclopropanation reactions of non-activated alkenes. Cyclopropanation of 1,3-butadienes with these intermediates also leads to the formation of cycloheptadienes (Entry 4, Table 2.24). 

A further synthetic approach to carbon-metal double bonds is based on the acid-catalyzed abstraction of alkoxy groups from a-alkoxyalkyl complexes [436 -439] (Figure 3.11). These carbene complex precursors can be prepared from alk-oxycarbene complexes (Fischer-type carbene complexes) either by reduction with borohydrides or alanates [23,55,63,104,439-445] or by addition of organolithium compounds (nucleophilic addition to the carbene carbon atom) [391,446-452]. 

Low-valent, 18-electron (Fischer-type) carbene complexes with strong n-acceptors usually are electrophilic at the carbene carbon atom (C ). These complexes can undergo reactions similar to those of free carbenes, e.g. cyclopropanation or C-H insertion reactions. The carbene-like character of these complexes becomes more pronounced when electron-accepting groups are directly bound to C (Chapter 4), whereas electron-donating groups strongly attenuate the reactivity (Chapter 2). 

Calculations performed for cyclopropanation with Fischer-type carbene complexes [28] indicate that the electrophilic attack of the carbene complex at the alkene and the final ring closure are concerted. Extrapolation from this result to the C-H insertion reaction (in which a a-bond instead of a 7i-bond is cleaved) suggests that C-H bond cleavage and the formation of the new C-C and C-H bonds might also be concerted (Figure 3.38). 

Although the applications of Fischer-type carbene complexes are discussed in Chapter 2, their use as catalysts for olefin metathesis (a minor aspect of the chemistry of these compounds) will be discussed in this section. 

Table 3.15. Fischer-type carbene complexes as catalysts for homogeneous-phase alkene metathesis.

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

Heteroatom-substituted allenylidene and higher odd-chain cumulenylidene complexes [M]=C(=C) =CR R ( = 1, 3, 5 R /R = NR2, OR, SR, SeR) are directly related to the classical Fischer-type carbene complexes, being regarded as their functional carbo-mers [5-7]. However, although two of the first allenylidene complexes synthesized were the amino-allenylidene derivatives [M =C=C=CPh (NMe2) 1(00)5] (M = Or, W) [8], the chemistry of these compounds has been much less developed [9, 10]. In fact, as aheady discussed in Chapter 6 the chemistry of metallacumulenes is largely dominated by the all-carbon substituted representatives... 

The starting Fischer-type carbene complexes 1 were obtained by Michael addition of dimethylamine to the carbon-carbon triple bond of the corresponding ethoxy-(phenylethynyl)carbenes. In this regard, de Meijere and co-workers observed that the reactions of several primary and secondary amines with this sort of carbenes, in particular chromium derivatives 3 containing bulky substituents at the terminal carbon of the acetylenic unit, result in formation of the aminoallenylidene derivatives 5 as by-products of the expected Michael adducts 4 (Scheme 2) [20-24]. 

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