Carbometallation pathways

The C-H/olefin coupling of aryloxazolines proceeds with unusual product selectivity. In this case, alkylation products, i.e., formally dehydrogenation products, are obtained as a major product (Eq. 22) [11]. These types of dehydrogenation compounds are believed to be formed via a carbometalation pathway. The first example of this type of alkenylation of arenes with olefins using palladium(II) complexes via C-H bond cleavage was reported in 1967 [32]. Later, several efforts were made to perform this reaction in a catalytic manner [33]. In 2001, Milstein et al. [34] reported the oxidative alkenylation of arenes with olefins using a Ru/02/C0 catalyst system (Eq. 23). Details of the reaction mechanism have not been elucidated. 

The Pd-catalyzed cross-coupling reaction of vinyl(2-pyridyl)silanes 5.48 with organic halides gave substituted vinyl(2-pyridyl)silanes 5.49 in high yields. The mechanism of this reaction involves the carbometallation pathways (Scheme 5.18). 

Simmons-Smith reagent that contradicts path B, and path A has therefore been widely believed to represent the experimental reality. For lithium carbenoids, on the other hand, the alternative carbometalation/cyclisation pathway has received experimental support. Actually, the factors that determine the... 

Despite the formal similarity of the reaction, the mechanism of Cp2ZrCl2-catalyzed ethylalumination [64] with AlEt3 is different from that of either methylalumination with AlMe3 or ethylalumination with Et2AlCl [62]. The involvement of dimetallic species was confirmed by NMR spectroscopy as well as deuterolysis (Scheme 8.31). The proposed mechanism features an interesting zwitterionic bimetallic species, in which the zirconium center is cationic. A highly instructive treatise on the mechanistic pathways of carbometalation is presented in [65],... 

Diyne cyclization/hydrosilylation catalyzed by 4 was proposed to occur via a mechanism analogous to that proposed for nickel-catalyzed diyne cyclization/hydrosilylation (Scheme 4). It was worth noting that experimental evidence pointed to a silane-promoted reductive elimination pathway. In particular, reaction of dimethyl dipropargylmalonate with HSiMc2Et (3 equiv.) catalyzed by 4 led to predominant formation of the disilylated uncyclized compound 5 in 51% yield, whereas slow addition of HSiMe2Et to a mixture of the diyne and 4 led to predominant formation of silylated 1,2-dialkylidene cyclopentane 6 (Scheme 5). This and related observations were consistent with a mechanism involving silane-promoted G-H reductive elimination from alkenylrhodium hydride species Id to form silylated uncyclized products in competition with intramolecular carbometallation of Id to form cyclization/hydrosilylation products (Scheme 4). Silane-promoted reductive elimination could occur either via an oxidative addition/reductive elimination sequence involving an Rh(v) intermediate, or via a cr-bond metathesis pathway. 

The key success of these metal-catalyzed processes lies in the replacement of an unachievable carbozincation by an alternative carbometallation involving the transition metal catalyst, or another pathway such as an alkene-alkene (or alkyne) oxidative coupling promoted by a group IV transition metal complex, followed by transmetallation. An organozinc is ultimately produced and the latter can be functionalized by reaction with electrophiles. 

Considering the mechanistic rationales of the transition metal-catalyzed enyne cycloisomerization, different catalytic pathways have been proposed, depending on the reaction conditions and the choice of metal catalyst [3-5, 45], Complexation of the transition metal to alkene or alkyne moieties can activate one or both of them. Depending on the manner of formation of the intermediates, three major mechanisms have been proposed. The simultaneous coordination of both unsaturated bonds to the transition metal led to the formation of metallacydes, which is the most common pathway in transition metal-catalyzed cycloisomerization reactions. Hydrometalation of the alkyne led to the corresponding vinylmetal species, which reacts in turn with olefins via carbometalation. The last possible pathway involves the formation of a Jt-allyl complex which could further react with the alkyne moiety. The Jt-allyl complex could be formed either with a functional group at the allylic position or via direct C-H activation. Here the three major pathways will be discussed in a generalized form to illustrate the mechanisms (Scheme 8). 

Several reactions in organometaUic chemistry also appear to contravene the rule, but which can be explained in a somewhat similar way. Hydrometallation [5.45, see (Section 5.1.3.4) page 162], carbometallation, metallo-metallation, and olefin metathesis reactions are all stereospecifically suprafacial [2 + 2] additions to an alkene or alkyne, for which the all-suprafacial pathway is forbidden. Hydroboration, for example, begins with electrophilic attack by the boron atom, but it is not fully stepwise, because electron-donating substituents on the alkene do not speed up the reaction as much as they do when alkenes are attacked by electrophiles. Nevertheless, the reaction is stereospecifically syn—there must be some hydride delivery more or less concerted with the electrophilic attack. The empty p orbital on the boron is the electrophilic site and the s orbital of the hydrogen atom is the nucleophilic site. These orbitals are orthogonal, and so the addition 6.126 is not pericyclic. 

However, when the Pd-TBAF system is used in the above reaction, the transmetallation from silicon to palladium can be accelerated by the fluoride ion and the reaction pathway is changed from carbometallation to transmetallation pathway (Scheme 5.19). 

Negishi, E.-i., Kondakov, D. Y., Choueiry, D., Kasai, K., Takahashi, T. Multiple Mechanistic Pathways for Zirconium-Catalyzed Carboalumination of Alkynes. Requirements for Cyclic Carbometalation Processes Involving C-H Activation. J. Am. Chem. Soc. 1996,118, 9577-9588. 

These are some of the many examples for C-H bond functionalization of (hetero)arenes that are proposed to follow CMD pathway. The pivotal role of base on the metal, mainly the acetato and carboxylate ion which acts as bases for abstraction of the C-H proton was highlighted through these examples. Besides the mechanisms that have been mentioned so far which are known to be operating in C-H activation of (hetero)arenes several others have also been proposed such as Heck type carbometalation mechanism and Se3 type mechanism. However, in this chapter we intend to focus on the more widely applicable ones, which have been described above. 

A new carbometallation/oxidation/C-C bond cleavage sequence for cyclopropenes allows the preparation of aldehyde enantiomers bearing a-quaternary stereocentres using different materials in two pathways as shown in Scheme 1." ... 

Zirconocene-catalyzed carbomagnesation of internal allylic ethers proceeds by a different pathway. The carbometallation of allylic ethers with the internal double bond gives formally the S 2 substitution product 15 with the loss of the ether moiety (Scheme 7). A few examples are given in Table 4. Especially interesting, from the synthetic point of view, is ethylmagnesation of cyclic ethers (the last entry in Table 4), because it opens a pathway to the synthesis of functionalized homoallylic alcohols [14]. An asymmetric variant of this reaction gives products with ees>90% [15]. 

The substitution pattern in the enolate is crucial for the ring size of the cyclization product. Upon reaction with carbene complex 58 /3-substituted lithium enolates 59a H) lead to densely substituted cyclopentanols 60 suggesting a [2-i-2-i-l]cycloaddition pathway. /3-Unsubstituted lithium enolates 59b (R =H), however, form 1,3,3,5-tetrasubstituted cyclohexane-l,4-diols 61 that indicates a [2-I-2-I-1-I-1] sequence [41]. The branching point in the mechanism seems to be intermediate B formed upon addition of the allyl magnesium bromide to penta-carbonylchromate intermediate A. Intermediate B formed from /3-substituted enolates 59a is supposed to undergo an intramolecular carbometallation reaction to give cyclopentanol derivative 60. In contrast, intermediate B originating from... 

In addition to energetic factors, the structure of the Ti-complex may play a crucial role on the performance of the catalytic reaction (Scheme 6) [34]. Alkyne insertion into the metal-sulfur bond via five-coordinated 7i-complex led to the formation of intermediate metal complex capable for direct C-S reductive elimination to complete product formation. In contrast, intermediate metal complex formed via alkyne insertion through the four-coordinated Ti-complex suffered from improper geometry configuration, which may block the whole catalytic cycle. An important issue related to reactivity of coordinated alkynes in such catalytic systems is C-Het vs. Het-Het bonds activation [35] and carbometallation vs. heterometallation pathways [36]. 

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