Generation of Acceptor-Substituted Carbene Complexes

Electrophilic transition metal complexes can react with organic ylides to yield alkylidene complexes. A possible mechanism would be the initial formation of alkyl complexes, which are converted into the final carbene complexes by electrophilic a-abstraction (Figure 3.18). This process is particularly important for the generation of acceptor-substituted carbene complexes (Section 4.1). 

Fig. 4.1. Generation of acceptor-substituted carbene complexes from ylides. X N2, SR2, S(0)Me2, Arl Z COR, CO2R, CONR2, SO2R, CN, P(0)(0R)2.

Electrophilic carbene complexes generated from diazoalkanes and rhodium or copper salts can undergo 0-H insertion reactions and S-alkylations. These highly electrophilic carbene complexes can, moreover, also undergo intramolecular rearrangements. These reactions are characteristic of acceptor-substituted carbene complexes and will be treated in Section 4.2. 

In contrast with non-acceptor-substituted carbene complexes, most of which are rather stable compounds, only few acceptor-substituted carbene complexes have been isolated [500,502,947,948]. In particular, acceptor-substituted carbene complexes relevant to organic synthesis (e.g. copper or rhodium acylcarbene complexes) are normally highly reactive and have remained elusive to spectroscopic characterization (for theoretical treatments, see Section 1.2). The inference that these intermediates are indeed carbene complexes is in part based on the observation that the modes of generation and the reactivity of these reactive species correlate well with those of less reactive carbene complexes. 

Because acceptor-substituted carbene complexes can normally not be isolated, generation must occur in the presence of a suitable substrate. If during carbene-transfer from the intermediate carbene complex to the substrate the complex L M (Figure 4.1) is regenerated, then catalytic amounts of this complex only will be... 

Acceptor-substituted carbene complexes are highly reactive intermediates, capable of transforming organic compounds in many different ways. Typical reactions include insertion into o-bonds, cyclopropanation, and ylide formation. Generally, acceptor-substituted carbene complexes are not isolated and used in stoichiometric amounts, but generated in situ from a carbene precursor and transition metal derivative. Usually only catalytic quantities of a transition metal complex are required for complete conversion of a carbene precursor via an intermediate carbene complex into the final product. 

Carbenes and transition metal carbene complexes are among the few reagents available for the direct derivatization of simple, unactivated alkanes. Free carbenes, generated, e.g., by photolysis of diazoalkanes, are poorly selective in inter- or intramolecular C-H insertion reactions. Unlike free carbenes, acceptor-substituted carbene complexes often undergo highly regio- and stereoselective intramolecular C-H insertions into aliphatic and aromatic C-H bonds [995,1072-1074,1076,1085,1086],... 

Table 4.17. Generation and rearrangement of azomethine ylides from acceptor-substituted carbene complexes and imines.

If chiral catalysts are used to generate the intermediate oxonium ylides, non-racemic C-O bond insertion products can be obtained [1265,1266]. Reactions of electrophilic carbene complexes with ethers can also lead to the formation of radical-derived products [1135,1259], an observation consistent with a homolysis-recombination mechanism for 1,2-alkyl shifts. Carbene C-H insertion and hydride abstraction can efficiently compete with oxonium ylide formation. Unlike free car-benes [1267,1268] acceptor-substituted carbene complexes react intermolecularly with aliphatic ethers, mainly yielding products resulting from C-H insertion into the oxygen-bound methylene groups [1071,1093]. 

When acceptor-substituted carbene complexes are generated in the presence of carbonyl compounds, carbonyl ylides can be formed. These intermediates can undergo a wide variety of further transformations [38,1079] (Figure 4.13). 

Fig. 4.16. Atypical reactions of carbonyl ylides generated from carbonyl compounds and acceptor-substituted carbene complexes [1276,1306],...

If acceptor-substituted carbene complexes are generated in the presence of thioethers, ylide formation is generally the mostly favored process. The resulting sulfonium ylides are often sufficiently stable to be isolated [975,1307-1309]. Typical reactions of sulfonium ylides include 1,2-alkyl migration, leading to products of... 

The most frequently used ylides for carbene-complex generation are acceptor-substituted diazomethanes. As already mentioned in Section 3.1.3.1, non-acceptor-substituted diazoalkanes are strong C-nucleophiles, easy to convert into carbene complexes with a broad variety of transition metal complexes. Acceptor-substituted diazomethanes are, however, less nucleophilic (and more stable) than non-acceptor-substituted diazoalkanes, and require catalysts of higher electrophilicity to be efficiently decomposed. Not surprisingly, the very stable bis-acceptor-substituted diazomethanes can be converted into carbene complexes only with strongly electrophilic catalysts. This order of reactivity towards electrophilic transition metal complexes correlates with the reactivity of diazoalkanes towards other electrophiles, such as Brpnsted acids or acyl halides. 

As mentioned in Sections 3.1.6 and 4.1.3, cyclopropenes can also be suitable starting materials for the generation of carbene complexes. Cyclopropenone di-methylacetal [678] and 3-alkyl- or 3-aryl-disubstituted cyclopropenes [679] have been shown to react, upon catalysis by Ni(COD)2, with acceptor-substituted olefins to yield the products of formal, non-concerted vinylcarbene [2-1-1] cycloaddition (Table 3.6). It has been proposed that nucleophilic nickel carbene complexes are formed as intermediates. Similarly, bicyclo[1.1.0]butane also reacts with Ni(COD)2 to yield a nucleophilic homoallylcarbene nickel complex [680]. This intermediate is capable of cyclopropanating electron-poor alkenes (Table 3.6). 

Interestingly, sulfonium ylides generated from electrophilic carbene complexes and sulfides can react with carbonyl compounds, imines, or acceptor-substituted alkenes to yield oxiranes [1320-1325], aziridines [1321,1326,1327] or cyclopropanes [1328,1329], respectively. In all these transformations the thioether used to form the sulfonium ylide is regenerated and so, catalytic amounts of thioether can be sufficient for complete conversion of a given carbene precursor into the... 

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