Carbenoid complexes insertion reactions

Interestingly, [Ee(F20-TPP)C(Ph)CO2Et] and [Fe(p2o-TPP)CPh2] can react with cyclohexene, THF, and cumene, leading to C-H insertion products (Table 3) [22]. The carbenoid insertion reactions were found to occur at allylic C-H bond of cyclohexene, benzylic C-H bond of cumene, and ot C-H bond of THF. This is the first example of isolated iron carbene complex to undergo intermolecular carbenoid insertion to saturated C-H bonds. 

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. 

Although C—H insertion reactions rarely occur in intermolecular reactions with diazoacetates, these are common side reactions with diazomalonates3132 (equation 10) and diazo ketones (with a-allyl vinyl ethers).33 Several mechanistic pathways are available to generate the products of an apparent direct C—H insertion reaction and these include dipolar intermediates, ir-allyl complexes and ring opening of cyclopropanes.1 Oxidative problems due to the presence of oxygen are common with copper catalysts, but these are rarely encountered with rhodium catalysts except in systems where the carbenoid is ineffectively captured.34... 

One of the attractions of dirhodium paddelwheel complexes is their ability to catalyse a wide variety of organic transformations such as C-H insertions, cyclopropanations and ylide formation. A review on the application of high symmetry chiral Rh2(II,II) paddlewheel compounds highlights their application as catalysts for asymmetric metal carbenoid and nitrenoid reactions, and as Lewis acids.59 Their impressive performance as catalysts in C-H functionalisation reactions has been exploited in the synthesis of complex natural products and pharmaceutical agents. A recent review on catalytic C-H functionalisation by metal carbenoid and nitrenoid insertion demonstrates the important role of dirhodium species in this field.60... 

The results above clearly demonstrate that donor/acceptor carbenoids (specifically those derived from aryldiazoacetates) are capable of better reactivity than their acceptor or acceptor/acceptor counterparts with certain catalysts. Cyclohexane, however, is not appropriate for examining the selectivity of intermolecular carbenoid C-H insertion reactions. In order to achieve selective transformations on more complex substrates, it would be crucial to determine what level of differentiation could be obtained between different types of C-H bonds. Thus Davies and coworkers studied the relative rate of insertion of methyl phenyldiazoacetate into a number of simple substrates through competition studies (Fig. 6) [81]. 

Although these carbenoids are usually discussed in relation to insertion reactions, some of them undergo polymerization and other reactions which are similar to those of the ylid. Thus, in ylid chemistry the (CH3) 3N+ group may be considered, as a pseudo-halogen. Although it has not been shown that the ylid reacts by an insertion reaction, it is possible that the conditions under which insertion can occur have not been realized. If the ylid is considered as a carbenoid, its polymerization reactions may proceed via a lithium halide complex. Alternatively, the complex may rearrange to the bromomethyllithium which may be the reactive intermediate. 

Rh-catalyzed asymmetric C—H bond functionalization via a carbene insertion reaction was extensively documented in the early days, especially the intramolecular reactions. Thanks to enormous efforts from the groups of Davies and Doyle, asymmetric intramolecular C—H bond insertion by Rh carbenoids has become a reliable methodology and has been employed frequently in the total synthesis of complex natural products. " " ... 

One important advantage of the intermolecular carbene insertion reactions is that simple starting materials can be employed and accordingly there is no need for the construction of complex substrates in advance. However, the intermolecular process requires a delicate balance between electronic and steric effects for metal carbenoids. On the other hand, there are several obstacles to be overcome, including chemo-, regio-, and enantioselectivity. Fortunately, great efforts have been devoted in the past decade and a series of carbene precursors and chiral Rh catalysts have been developed, so satisfactory yields and ee can be obtained in some catalytic systems. Generally, suitable carbene precursors, such as donor/acceptor diazo compounds, could reduce the chance of side product formation due to carbene dimerization. 

The asymmetric allylic C—H bond insertion reaction of 1,4-cyclohexadiene was further improved by Denton and Davies in 2009. Using different donor/ acceptor carbenoids derived from a-aryl-a-diazoketones 25 and a chiral dirhodium complex Rh2(S-PTAD)4 instead of methyl phenyldiazoacetate la and Rh2(S-DOSP)4 in previous work (Scheme 1.6, eqn (1)), the corresponding C—H bond insertion products 26 could be obtained in up to 90% yield and 89% ee in refluxing DMB (Scheme 1.7a). Later, the catalytic efficiency was significantly enhanced by conducting the reaction under solvent-free con-ditions. Since donor/acceptor carbenoids are more stable and less prone to catalyst decay and carbene dimerization, they are suitable for reactions... 

Apart from the extensively documented dirhodium catalysts, several ehiral Ir complexes have lately also been shown to be catalytically efficient in the asymmetric C—H bond insertion reactions of metal carbenoids and they offer eom-plementary reaetivity profiles. In general, 1,4-cyclohexadienes and THF are two commonly used model substrates. Several groups, including Katsuki, " Che, and Musaev, Davies, and Blakey, have realized the intermoleeular C—H bond insertion reaetion of 1,4-cyclohexadienes and THF by diverse ehiral Ir complexes (Figure 1.5). 

In the second type of process the metal acts as a carbenoid and inserts into the C—H bond, a process generally termed oxidative addition in organometallic chemistry (equation 1 b). This reaction is believed to go via the same sort of alkane complex as in the Shilov system, but, instead of losing a proton, it goes instead to an alkylmetal hydride. This may be stable, in which case it is observed as the final product, or it may react further. 

Liang Y, Zhou H, Yu Z-X (2009) Why is copper (I) complex more competent than dirhodium(ii) complex in catalytic asymmetric O-H insertion reactions A computational study of the metal carbenoid O-H insertion into water. J Am Chem Soc 131 17783-17785... 

Tryptophan offers an indole side chain that can be used for ligation chemistry. A water-compatible rhodium carbene can be added to the indole ring (19) [105,139]. The reactive species is generated in situ by a conjugated diazo compound by a rhodium catalyst like rhodium(II) acetate [63,139,149]. The reaction takes place in the two- and three-position of indole. Thus, a mixture of N-alkylated and C-alkylated product is obtained. It is necessary to add hydroxylamine hydrochloride as an additive to bind to the distal rhodium carbenoid complex. The usage of this salt lowers the pH value below 3.5 and therefore limits the scope of this methodology. As a side reaction, the carbene inserts into the O-H bond of water (Table 6). 

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. 

Synthesis of (+)-Indatraline and (+)-Cetiedil While the intermolecular C—H insertion reactions induced by dirhodium (II) complexes were considered for a long time as not synthetically useful, Davies et al. demonstrated that rhodium carbenoids derived from diazo compounds... 

Cyclic a-diazocarbonyl compounds (59) and enynones (61) have been used as Rh-and Zn-carbenoid precursors, respectively. Cyclic derivatives (59) have been found to favour intermolecular Rh-catalysed cyclopropanation reactions, relative to the formation of conjugated alkene (60) by intramolecular -hydride elimination as is usually observed in the case of a-alkyl-a-diazocarbonyl compounds this high level of chemoselectivity is reported for the first time. Rh-carbenoids derived from (59) have also promoted cyclo-propenation reactions as well as diverse X-H insertion reactions (i.e., X = C, N, O, S). In parallel, highly functionalized cyclopropylfiirans (62) have been successfiilly prepared from an alkene and an enynone (61) by a cyclization/cyclopropanation sequence conducted in the presence of catalytic amounts of ZnCl2, which is cheap and of low toxicity computations support the probable participation of intermediate Fisher-type Zn(II) carbene complexes (63). 

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