Rhodium-carbene intermediates

It is commonly accepted that rhodium-carbene intermediates are the active species preceding the C-C bond-forming insertion step (cf. Scheme 1 with M = Rh). The in situ generation of carbenes is in line with the characteristics of diazoalkane reactivity [1, 2]. However, neither has the carbenoid primary adduct B been observed nor is there any spectroscopic evidence of the metal-earbene species C. It is likely that the electrophilic addition of the active catalyst A (e. g., sol-... 

By analogy with the rhodium carbene intermediate proposed in the C H insertion reaction with diazo compounds, C— H amination is believed to proceed via a rhodium nitrene species, although such an intermediate has never been characterized. However, as chiral dimeric rhodium complexes lead to the formation of enantioen-riched amination products, it suggests that the metal center is closely associated with the reactive nitrogen during the C—H insertion step. Both a rhodium nitrene or rhodium phenyliminoiodinane species may be involved (Figure 5.2). 

Many rhodium(II) complexes are excellent catalysts for metal-carbenoid-mediated enantioselective C-H insertion reactions [101]. In 2002, computational studies by Nakamura and co-workers suggested the dirhodium tetracarboxylate catalyzed diazo compounds insertion reaction to alkanes C-H bonds proceed through a three-centered hydride-transfer-like transition state (Fig. 25) [102]. Only one rhodium atom of the catalyst is involved in the formation of rhodium carbene intermediate, while the other rhodium atom served as a mobile ligand, which enhanced the electrophilicity of the first one and facilitate the cleavage of rhodium-carbon bond. In this case, the metal-metal bond constitutes a special example of Lewis acid activation of Lewis acidic transition-metal catalyst. 

Step 1 involves the complexation of 1 with the Rh(II) catalyst and step 2 (the rate-determining step) is the generation of the rhodium carbene intermediate 4 by decomposition of complex 3. We should point out that step 3, the reaction of the carbene 4 with triethylsilane, is a fast step that has no influence on the current study. 

Recently, Aumann et al. reported that rhodium catalysts enhance the reactivity of 3-dialkylamino-substituted Fischer carbene complexes 72 to undergo insertion with enynes 73 and subsequent formation of 4-alkenyl-substituted 5-dialkylamino-2-ethoxycyclopentadienes 75 via the transmetallated carbene intermediate 74 (Scheme 15, Table 2) [73]. It is not obvious whether this transformation is also applicable to complexes of type 72 with substituents other than phenyl in the 3-position. One alkyne 73, with a methoxymethyl group instead of the alkenyl or phenyl, i.e., propargyl methyl ether, was also successfully applied [73]. 

While metalloporphyrin carbene complexes are well established for ruthenium and osmium, they are less well known for rhodium. Cationic rhodium porphyrin carbene intermediates were implicated in a report by Callot et al. in w- hich... 

Rh(Por)l (Por = OEP. TPP, TMP) also acts as a catalyst for the insertion of carbene fragments into the O—H bonds of alcohols, again using ethyl diazoacetate as the carbene source. A rhodium porphyrin carbene intermediate was proposed in the reaction, which is more effective for primary than secondary or tertiary alcohols, and with the bulky TMP ligand providing the most selectivity. ... 

Both rhodium and osmium porphyrins are active for the cyclopropanation of alkenes. The higher activity of the rhodium porphyrin catalysts can possibly be attributed to a more reactive, cationic carbene intermediate, which so far has defied isolation. The neutral osmium carbene complexes are less active as catalysts but the mono- and bis-carbene complexes can be isolated as a result. 

A rhodium-catalyzed intramolecular C-H functionalization has been employed for the synthesis of bicyclic imidazoles. The alkene acts as an anchor to the metal, directing the C-H functionalization process, which involves the formation of an Rh(l) carbene intermediate (Equation (118)).107... 

The axial alignment of Rh2(5R-MEPY)4 leads to probable structures for the carbene intermediate as shown in Figure 17.15. Approach of styrene will occur with the phenyl group pointing away from the rhodium complex, and also in a trans (anti) fashion with respect to the ester group of the carbene moiety. The 2-phenylcyclopropane-l-carboxylic ester resulting from this is indeed the 1R,2R (1R-trans) diastereomer. 

An understanding of the mechanism [10] for rhodium-mediated intramolecular C-H insertion begins with the recognition that these a-diazo carbonyl derivatives can also be seen as stabilized ylides, such as 15 (Scheme 16.4). The catalytic rhodium(II) car-boxylate 16 is Lewis acidic, with vacant coordination sites at the apical positions, as shown. The first step in the mechanism, carbene transfer from the diazo ester to the rhodium, begins with complexation of the electron density at the diazo carbon with an open rhodium coordination site, to give 17. Back-donation of electron density from the proximal rhodium to the carbene carbon, with concomitant loss of N2, then gives the intermediate rhodium carbene complex 18. 

The mechanism by which this intermediate rhodium carbene complex 18 reacts can be more easily understood if it is written as the inverted ylide 19, as this species would clearly be electrophilic at carbon. We hypothesized that for bond formation to proceed, a transition state 20 in which the C-Rh bond is aligned with the target C-H bond... 

In 1981 it was shown that rhodium(II) carboxylates smoothly catalyze the addition of ethyl diazoacetate to a variety of alkanes11. While some differentiation between possible sites of insertion was observed, selectivity is not as high for this carbenoid process as it is for the free radical process above. Rhodium-catalyzed intermolecular C-H insertion is thought to proceed via electrophilic addition of an intermediate rhodium carbene into the alkane C—IT bond. 

Transition-metal catalysis, especially by copper, rhodium, palladium and ruthenium compounds, is another approved method for the decomposition of diazo compounds. It is now generally accepted that short-lived metal-carbene intermediates are or may be involved in many of the associated transformations28. Nevertheless, these catalytic carbene transfer reactions will be fully covered in this chapter because of the close similarity in reaction modes of electrophilic carbenes and the presumed electrophilic metal-carbene complexes. 

Pyridone is O-alkylated more readily than normal amides, because the resulting products are aromatic. With soft electrophiles, however, clean N-alkylations can be performed (Scheme 1.7). The Mitsunobu reaction, on the other hand, leads either to mixtures of N- and O-alkylated products or to O-alkylation exclusively, probably because of the hard, carbocation-like character of the intermediate alkoxyphosphonium cations. Electrophilic rhodium carbene complexes also preferentially alkylate the oxygen atom of 2-pyridone or other lactams [20] (Scheme 1.7). 

Rearrangement of N-nitrosoamides. N-Nitrosamides (1), prepared by acetylation of primary amines followed by nitrosation, are known to decompose in nonpolar solvents at 80-100° to form alkyl acetates with elimination of nitrogen.9 The presumed diazoalkane intermediate (a) can be trapped as a rhodium carbene (b), which undergoes rearrangement to an alkene (equation I). The overall result is a mild, nonbasic version of the classical Hofmann degradation of amines. 

In CHEC-II(1996), carbene insertion reactions into the N-H bond to form a fused-ring azetidinone warranted a separate section. In the last decade, the popularity to this approach to bicyclic systems seems to have markedly declined. Nevertheless, dirhodium tetraacetate and rhodium octanoate were used to generate the corresponding bicyclic compounds from the diazo compounds 241 (R2 = H and /3-Me), respectively, via the carbene intermediates. In the latter case, the produced enol was esterified and then the ester group replaced with a hydroxymethyl substituent to give derivatives 242 in a one-pot process <2001JCM166, 1999TL427>. 

Reaction 7.34 involves a metal-carbene intermediate, while reaction 7.35 involves nucleophilic attack by the diazo compound to the coordinated alkene. With a rhodium-porphyrin catalyst direct spectroscopic evidence has been obtained for the carbene pathway (see Section 2.5.2). 

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... 

For the rhodium-catalyzed cyclopropanation of olefin substrates with activated allylic C—H groups, the selectivity between cyclopropanation and C—H insertion is sometimes unsatisfactory. Very recently, Davies and Thompson (128) reported a selective silver-catalyzed cyclopropanation of olefins to give predominately cyclopropane products. Aryldiazoacetates were used as carbene precursors with the aryl groups helping to stabilize the carbene intermediate and facilitate the reaction. Notably, phenallyldiazoacetate with different olefins also gave cyclopropane products (Fig. 26). 

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. 

Rhodium-mediated intermolecular C— H insertion is thought to proceed via oxidative addition of an intermediate rhodium carbene into the alkane C—H bond. Evidence that the rhodium and its ligands are directly associated with the product-determining transition state has been put forward by Callot, who ob-... 

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