Activation of the C-X bond

The use of chiral Brpnsted acid catalysis as a mode of asymmetric activation burgeoned dramatically in the early part of the twenty first century [35]. The role of hydrogen in this process is, in essence, similar to that of Lewis acid catalysts - i.e. activation of the C=X bond (X=0, NR, CR ) by decreasing the LUMO energy and ultimately leading to promotion of nucleophilic addition to the C=X bond (Fig. 1.5). 

In this chapter, the applications of douhle-functionalized arenes in the synthesis of five-memhered heterocycles will he discussed. The eontents are divided according to the different types of substrates applied. The subchapters are organized based on the types of nucleophiles o/t/jo-substituted to aryl halides. For the heterocycle synthesis based on C-X bond activation, in general, transition metal catalyst promoted activation of the C-X bond initiated the reaction sequence and was followed by intramolecular or intermolecular cyclization. 

Currently, one of the most sought after procedures in organometallic chemistry is a homogeneous catalytic cycle that involves the activation of a C-H bond in an alkane. We have just examined the oxidative addition of C-X bonds, and in Section 12.3 we will show how this activation of the C-X bond leads to further chemistry. Regardless of how useful this may be, one still needs a C-X bond to start. It would be very useful to directly activate a C-H bond in an alkane, without needing to first create a C-X bond. However, the oxidative addition of a standard C-H bond is a rare reaction. A handful of systems have been developed, and we discuss two. No homogeneous catalytic cycles have yet to be developed, so the examples are simply stoichiometric reactions. 

Another important characteristic of radical abstraction reactions is the force constants of the ruptured and the generated bonds. The dependence of the activation energy for the reactions of the type R + R X > RX + R1, where X = H, Cl, Br, or I, on the coefficients Ai and Af was demonstrated experimentally [17]. It was found that parameter re = const in these reactions, while the square root of the activation energy for a thermally neutral reaction is directly proportional to the force constant of the ruptured bond. The smaller the force constant of the C—X bond, the lower the Ee0, and the relationship Feo12 to A(1 I a) 1 is linear (see Figure 6.4). The same result was also obtained for the reactions of hydrogen atoms with RC1, RBr, and RI [17]. 

During the past two decades, within the series of our studies, we have developed a silylative coupling reaction of olefins with vinylsubstituted siHcon compounds which takes place in the presence of transition-metal complexes (e.g. mthenium and rhodium) that initially contain or generate M—H and M—Si bonds (for reviews, see Refs [5] and [6]). The reaction involves activation of the =C—H bond of olefins and cleavage of the =C—Si bond of vinylsilane. The reaction, which is catalyzed by complexes of the type [ M( x-OSiMe3)(cod) 2] (where M = Rh, Ir) occurs according to Equation 14.12 [71, 72). 

Analogously, solvent effects on alkene formation in Sn 1 and Ei reactions can be predicted [16, 44]. Owing to the fact that the first step in both reactions, the heterolysis of the C—X bond, is exactly the same, we have to consider the activated complexes which lead to either the alkene or substitution product. 

The original idea of cationic grafting produced by initiation from a polymer containing cocatalytic moieties was proposed by Plesch in 1958 Basically, the principle of this branching reaction relies on activation of a C—X bond of the polymer by a Lewis acid in a process thought to proceed by halide ion abstraction ... 

Clearly, the first step in the carbonylation of allylic and benzylic derivatives to 3,4-unsaturated carboxylie acid derivatives and arylacetic acid derivatives, respectively, requires activation of a C-X bond at an sp -hybiidized carbon atom. Such activation could proceed either via nueleophilic attack with anionic, 18-electron metal complexes, whieh has been described, e. g., with cobalt [2]... 

A more detailed analysis of the radical mechanisms has been presented . Generally, all three processes show first-order kinetics but Ej reactions do not exhibit an induction period and are unaffected by radical inhibitors such as nitric oxide, propene, cyclohexene or toluene. For the non-chain mechanism, the activation energy should be equivalent to the homolytic bond dissociation energy of the C-X bond and within experimental error this requirement is satisfied for the thermolysis of allyl bromide For the chain mechanism, a lower activation energy is postulated, hence its more frequent occurrence, as the observed rate coefficient is now a function of the rate coefficients for the individual steps. Most alkyl halides react by a mixture of chain and E, mechanisms, but the former can be suppressed by increasing the addition of an inhibitor until a constant rate is observed. Under these conditions a mass of reliable reproducible data has been compiled for Ej processes. Necessary conditions for this unimolecular mechanism are (a) first-order kinetics at high pressures, (b) Lindemann fall-off at low pressures, (c) the absence of induction periods and the lack of effect of inhibitors and d) the absence of stimulation of the reaction in the presence of atoms or radicals. 

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