Activation of C-X bonds

In the case of a palladium-catalyzed carbonylative activation of C-X bonds, a general reaction mechanism is shown in Scheme 1.8. Normally this type of reaction starts from Pd(0) and is followed by the oxidative additional step and the coordination and insertion of CO to form the acylpalladium complex as the key... 

In the following ten chapters we wiU look at the details of the transitional metal-catalyzed carbonylative activation of C-X bonds. Depending on the nucleophiles used, their reactions mechanisms are different and have their own term as well. For example, alkoxycarbonylation refers to using alcohols as nucleophiles, aminocarbonylation means using amines as nucleophiles, and so on. Each type of reaction will be discussed separately and end with a personal prediction. 

Activation of C=X Bonds. Lewis acid activation of carbonyl compounds by ZnBr promotes the addition of allylsilanes and silyl ketene acetals. Addition to imines has also been reported. In general, other Lewis acids have been found to be more useful, though in some instances ZnBr has proven to be advantageous (eq 12). ... 

Activation of C-X Bonds. Even more important than carbonyl activation, ZnBr promotes substitution reactions with suitably active organic halides with a variety of nucleophiles. Alkylation of silyl enol ethers and silyl ketene acetals using benzyl and allyl halides proceeds smoothly (eq 13). Especially useful electrophiles are a-thio halides which afford products that may be desulfurized or oxidatively eliminated to result in a,p-unsaturated ketones, esters, and lactones (eq 14). Other electrophiles that have been used with these alkenic nucleophiles include Chloromethyl Methyl Ether, HC(OMe)3, and Acetyl Chloride... 

Activation of C=X Bonds. The mild Lewis acid character of ZnCl2 is frequently exploited to promote the addition of various nucleophiles to carbon-heteroatom double bonds. The well-established Knoevenagel condensation and related reactions have been effectively catalyzed by ZnC (eq 26). " The addition of enol ethers and ketene acetals to aldehydes and ketones has been noted (eq 27), though ZnCl2 has been used less widely in these aldol-type condensations than other Lewis acids, including TiCU,... 

Activation of C-X Bonds. The activation of C-X single bonds toward nucleophilic substitution is also mediated by the Lewis acidic character of ZnCl2. Benzylic (eq 33), allylic (eq 34), propargylic, and tertiary halides (eq 35) undergo substitution with mild carbon and heteroatom nucleophiles. 

The activation of C—H bonds and C—C bonds has attracted much attention in both academic and industrial laboratories because of their potential economic and ecological advantages. In the field of asymmetric synthesis, enantioselective catalytic C—X bond formation via the activation of C—H bonds and/or C—C bonds should have a great impact on asymmetric synthesis in both theory and practice. In theory, it is interesting to see how these very unreactive bonds can react preferentially in the presence of more reactive bonds with asymmetric control. In a practical sense, such C—H and C—C bonds are equivalent to the C M bonds in organometaUic reactions and would turn the corresponding stoichiometric amounts of metal into catalytic amounts. Conceptually, there are two fundamental ways to... 

The transition metal activates the C-X bond in the oxidative addition step and normally the substrates have sp or sp carbons at or immediately adjacent to an electrophilic centre. The reactivity of aliphatic C-X bond towards the oxidative addition with a transition metal is somewhat low. However, in 1992, Suzuki and co-workers discovered that Pd(PPh3)4 can catalyze couplings of alkyl iodides with alkyl boranes at 60°C in moderate yields (50-71%). These conditions tolerated a wide variety of functional groups such as esters, ketals and cyanides. 

The first step of the catalytic cycle constitutes the oxidative addition of the organic halide to the Pd catalyst, yielding a c/5-palladium(Il) species, which subsequently isomerizes to the more stable trans form [8]. Theoretical studies so far have focused on the molecular mechanism of C-X bond activation and the influ-... 

Oxidative addition of C-X bonds to Pd is an exothermic reaction, at least in the cases studied so far. From a theoretical point of view, it is important to note that relativistic effects are essential for the accurate theoretical prediction of the reaction enthalpy of oxidative addition, while the influence on the activation barriers appears to be much smaller [11]. These effects can nowadays be included in a standard way using commonly available program packages. 

Backbonding in coordinated halo-olefins activates the =C—X bond due to contribution of X-orbitals to the antibonding MO s 202,285)... 

The authors established directly the time scale for activation of C-H bonds in solutions at room temperature by monitoring the C-H bond activation reaction in the nanosecond regime with infrared detection. In the first stage of the process, loss of one carbon monoxide ligand (reaction VI-7 —- VI-8 in Scheme VI.6) substantially reduces back-bonding from the rhodium ion and increases the electron density at the metal center. Formed after the solvation stage, complex VI-9 traverses a 4.2 kcai nriol barrier (A = 5.0 x lo s ) and forms the -pCTp complex VI-10 which is more reactive toward C-H oxidative addition. 

In this chapter we have discussed the carbonylative transformations of C-X bonds using amines, alcohols and water as nucleophiles. From a reaction mechanism point of view, they all go through a nucleophilic attack on the acylmetal species by nucleophiles. No reductive elimination step was involved, and the active catalyst was regenerated under the assistant of base. 

Willis has similarly noted that indoles can be prepared via the cascade coupling of the aryl-halide and vinyl-triflate bonds in styrene 21 with primary amines (Scheme 6.41). Despite the fact that two different types of C—X bonds must be activated, this process proceeds with a single palladium catalyst (Pd2dba3/Xantphos), and a range of primary amines, carbamates and amides. More recently, even vinyl chlorides were found to participate in this coupling reaction [53]. 

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