Bond insertion, rhodium carboxylates

In a direct competition between 1,2- and 1,5-insertion into methylene C —H bonds, the relative proportion of products depends on the rhodium carboxylate employed. Rhodium(II) pivalate is the most efficient catalyst so far found for the cyclization of methyl 2-diazo-10-undecenoate. In contrast, rhodiumfll) trifluoroacetate gives a 52 48 ratio of cyclic 5/acyclic 6 products. 

Hubert in 1976 reported that rhodium acetate efficiently catalyzes diazo insertion into an alkene, to give the cyclopropane. In 1979, Southgate and Ponsford reported that rhodium acetate also catalyzes diazo insertion into a C—H bond. Prompted by these studies, Wenkert then demonstrated that cyclization of (58) to (59) proceeded much more efficiently with the rhodium carboxylates than it had with copper salt catalysis (equation 23). ... 

Carbenoid insertions. The species generated from decomposition of diazo compounds in the presence of rhodium carboxylates are capable of inserting into various X-H bonds. Thus, N-C bond formation has been exploited for the preparation of precursors of indoles, oxazoles, and peptides. ... 

Rhodium carboxylates. 13, 266-269 15, 278-280 16, 289-292 17, 298-302 a-Alkoxy esters. Rhodium carbenoids derived from a-diazo esters undergo O-H bond insertion in the reaction with alcohols or phenols. Low to moderate asymmetric induction from chiral esters is observed. ... 

Iwasawa et al. [21] also reported chelation-assisted reactions in an article entitled Rhodium(I)-Catalyzed Direct Carboxylation of Arenes with CO2 via Chelation-Assisted C-H Bond Activation, in which the cyclometalation reactions proceed easily and form cyclometalation intermediates. The metal atoms are active centers in their intermediates. Hence, the active metal atom reacts easily with inert carbon dioxide to give carboxylic acid derivatives. Examples include the cyclometalation of 2-phenylpyridine as a substrate in the presence of a rhodium intermediate. Carbon dioxide can be inserted into the rhodium-phenyl carbon bond, and a methyl ester is formed with TMSCH2N2 from a rhodium carboxylate, as shown in Eq. (6.5). The reaction mechanism is proposed as shown in Scheme 6.2 [21]. 

Carbonyl carbenes insert into various X—H bonds (X = O, N, C) in the presence of rhodium carboxylates. An application of the insertion of carbalkoxy carbene into the OH group of alcohols is illustrated by a synthesis of chorismic acid [104]. 

Rhodium carboxylates have been found to be effective catalysts for intramolecular C—H insertion reactions of a-diazoketones and esters. In flexible systems, five-membered rings are formed in preference to six-membered ones. Insertion into a methine carbon-hydrogen bond is preferred to insertion at a... 

Similar to the intramolecular insertion into an unactivated C—H bond, the intermolecular version of this reaction meets with greatly improved yields when rhodium carbenes are involved. For the insertion of an alkoxycarbonylcarbene fragment into C—H bonds of acyclic alkanes and cycloalkanes, rhodium(II) perfluorocarb-oxylates 286), rhodium(II) pivalate or some other carboxylates 287,288 and rhodium-(III) porphyrins 287 > proved to be well suited (Tables 19 and 20). In the era of copper catalysts, this reaction type ranked as a quite uncommon process 14), mainly because the yields were low, even in the absence of other functional groups in the substrate which would be more susceptible to carbenoid attack. For example, CuS04(CuCl)-catalyzed decomposition of ethyl diazoacetate in a large excess of cyclohexane was reported to give 24% (15%) of C/H insertion, but 40% (61 %) of the two carbene dimers 289). 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

The catalytic activity of rhodium diacetate compounds in the decomposition of diazo compounds was discovered by Teyssie in 1973 [12] for a reaction of ethyl diazoacetate with water, alcohols, and weak acids to give the carbene inserted alcohol, ether, or ester product. This was soon followed by cyclopropanation. Rhodium(II) acetates form stable dimeric complexes containing four bridging carboxylates and a rhodium-rhodium bond (Figure 17.8). 

Few examples of preparatively useful intermolecular C-H insertions of electrophilic carbene complexes have been reported. Because of the high reactivity of complexes capable of inserting into C-H bonds, the intermolecular reaction is limited to simple substrates (Table 4.9). From the results reported to date it seems that cycloalkanes and electron-rich heteroaromatics are suitable substrates for intermolecular alkylation by carbene complexes [1165]. The examples in Table 4.9 show that intermolecular C-H insertion enables highly convergent syntheses. Elaborate structures can be constructed in a single step from readily available starting materials. Enantioselective, intermolecular C-H insertions with simple cycloalkenes can be realized with up to 93% ee by use of enantiomerically pure rhodium(II) carboxylates [1093]. 

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. 

Since the observation that Rh(II) carboxylates are superior catalysts for the generation of transient electrophilic metal carbenoids from a-diazocar-bonyls compounds, intramolecular carbenoid insertion reactions have assumed strategic importance for C-C bond construction in organic synthesis [1]. Rhodium(ll) compounds catalyze the remote functionalization of carbon-hydrogen bonds to form carbon-carbon bonds with good yield and selectivity. These reactions have been particularly useful in the intramolecular sense to produce preferentially five-membered rings. 

A study of Rh2Ln4-catalyzed decomposition of 2-diazo-A-phenylmalo-namic acid ethyl ester 128 (R = C02Et) showed, that with perfluorocarbox-amides as catalyst ligands, the aromatic C—H insertion giving rise to oxindoles 129 occurs in preference to aliphatic C—H insertion, addition to C=C and C=C bonds, O—H insertion, and ylide formation, all of which are observed simply by switching to a carboxylate-based rhodium catalyst (94JOC2447). 

This mechanistic hypothesis led to two predictions. The first was that, since the product-determining step would seem to be oxidative addition of an electron deficient Rh center into the C—H bond, a C—H bond near an electron-withdrawing group should be less reactive than an isolated C—H bond. This prediction was borne out remarkably well by the work of Stork and Nakatani. They demonstrated that cyclization of (86) proceeds to give exclusively (87 equation 30). Thus, a C—H bond even 3 to the electron-withdrawing carboxyl group is much less reactive toward rhodium-mediated C—H insertion than is an isolated aliphatic C—H bond. 

Similar to the intramolecular insertion into an unactivated C—H bond, the intermolecular version of this reaction meets with greatly improved yields when rhodium carbenes are involved. For the insertion of an alkoxycarbonylcarbene fragment into C—H bonds of acyclic alkanes and cycloalkanes, rhodium(II) perfluorocarb-oxylates rhodium(II) pivalate or some other carboxylates and rhodium-... 

Although the first catalysts were copper-based, the insertion of metal-associated carbenes into carbon-hydrogen bonds has undergone a renaissance with the advent of rhodium(II) carboxylate catalysts [56]. Metal-catalyzed enan-tioselective C-H insertions of carbenes have not been studied in great detail. Most of the efficient enantioselective versions of this reaction involve chiral rhodium complexes and until recently, the use of chiral catalysts derived from metals other than copper and rhodium for the asymmetric C-H insertion of metal-associated carbenes are still unexplored. 

Rhodium complexes generated from A-functionalized (S)-proline 3.60 [933, 934, 935] or from methyl 2-pyrrolidone-5-carboxylates 3.61 [936, 937, 938] catalyze the cyclopropanation of alkenes by diazoesters or -ketones. Diastereoisomeric mixtures of Z- and E-cydopropylesters or -ketones are usually formed, but only the Z-esters exhibit an interesting enantioselectivity. However, if intramolecular cyclopropanation of allyl diazoacetates is performed with ligand 3.61, a single isomer is formed with an excellent enantiomeric excess [936,937], The same catalyst also provides satisfactory results in the cyclopropanation of alkynes by menthyl diazoacetate [937, 939] or in the intramolecular insertion of diazoesters into C-H bonds [940]. 

Cyclopropanation with alkyl dlazoacetates. Rhodium(Il) acetate is an efficient catalyst for the insertion of carboethoxycarbene into activated C-H-bonds (5, 571-572), but it is less effective than rhodium(II) n-butanoate or pivalate for catalysis of cyclopropanation of alkenes with alkyl diazoacetates, possibly because the latter carboxylates are more soluble in organic solvents. However, rhodium(ll) trifluoroacetate is readily soluble, but it is a poor catalyst for cyclopropanation. The alkyl group of the diazoacetate strongly influences the yields, which are highest with n-butyl diazoacetate. 

The interpretation of the formation of the Ci3-lactone requires a sequence of mechanistical pathways which are unknown so far in rhodium-catalysis. Two proposals for the mechanism were given in Equation 12. The mechanism of path B is similar to that shown for palladium catalysis. A rhodium Cg-carboxylate complex is formed which under further incorporation of butadiene could yield the lactone. In the mechanism of path A three molecules of butadiene react with the starting rhodium compound forming a C- 2 Chain, which is bound to the rhodium by two n -ally1 systems and one olefinic double bond. Carbon dioxide inserts into one of the rhodium allyl bonds thus forming a C- 3-carboxyl ate complex, which yields the new C-13-lactone. 

Demonceau, A., Noels, A.F., Hubert, A.J., and Theyssi6, P. (1984) Transition-metal-catalysed reactions of diazoesters. Insertion into C-H bonds of paraffins catalysed by bulky rhodium (II) carboxylates enhanced attack on primary C-H bonds. Bull. Soc. Chim. Belg., 93, 945-948. 

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