Alkenyl halides oxidative addition

Among many substrates used for Pd(0)-catalyzed reactions, organic halides are most widely used. In Grignard reactions, Mg(0) metal reacts with organic halides of sp carbons (alkyl halides) more easily than halides of sp carbons (aryl and alkenyl halides). On the other hand, Pd(0) complexes react more easily with halides attached to sp carbons, namely aryl and alkenyl halides. In addition, several pseudohalides are used as well. They undergo facile oxidative addition to Pd(0) to form Pd complexes which have cr-Pd-carbon bonds. Scheme 3.1 summarizes the oxidative addition of phenyl halides and pseudohalides to form phenylpalladium halides. Aryl iodides and bromides have been used widely. 

The reactions of the second class are carried out by the reaction of oxidized forms[l] of alkenes and aromatic compounds (typically their halides) with Pd(0) complexes, and the reactions proceed catalytically. The oxidative addition of alkenyl and aryl halides to Pd(0) generates Pd(II)—C a-hondi (27 and 28), which undergo several further transformations. 

Several types of Pd-catalyzed or -promoted reactions of conjugated dienes via TT-allylpalladium complexes are known. The Pd(II)-promoted oxidative difunctionalization reactions of conjugated dienes with various nucleophiles is treated in Chapter 3, Section 4, and Pd(0)-catalyzed addition reactions of conjugated dienes to aryl and alkenyl halides in this chapter. Section 1.1.1. Other Pd(0)-catalyzed reactions of conjugated dienes are treated in this section. 

The electrophilic character of the palladium atom in the complexes formed by oxidative addition of aryl halides and alkenyl halides to palladium(o) complexes can be exploited in useful ways. 

The general mechanism of coupling reactions of aryl-alkenyl halides with organometallic reagents and nucleophiles is shown in Fig. 9.4. It contains (a) oxidative addition of aryl-alkenyl halides to zero-valent transition metal catalysts such as Pd(0), (b) transmetallation of organometallic reagents to transition metal complexes, and (c) reductive elimination of coupled product with the regeneration of the zero-valent transition metal catalyst. 

Transition metal complexes that are easy to handle and store are usually used for the reaction. The catalytically active species such as Pd(0) and Ni(0) can be generated in situ to enter the reaction cycle. The oxidative addition of aryl-alkenyl halides can occur to these species to generate Pd(II) or Ni(II) complexes. The relative reactivity for aryl-alkenyl halides is RI > ROTf > RBr > RC1 (R = aryl-alkenyl group). Electron-deficient substrates undergo oxidative addition more readily than those electron-rich ones because this step involves the oxidation of the metal and reduction of the organic aryl-alkenyl halides. Usually... 

The general catalytic cycle for the coupling of aryl-alkenyl halides with alkenes is shown in Fig. 9.6. The first step in this catalytic cycle is the oxidative addition of aryl-alkenyl halides to Pd(0). The activity of the aryl-alkenyl halides still follows the order RI > ROTf > RBr > RC1. The olefin coordinates to the Pd(II) species. The coordinated olefin inserts into Pd—R bond in a syn fashion, p-Hydrogen elimination can occur only after an internal rotation around the former double bond, as it requires at least one /I-hydrogen to be oriented syn perpendicular with respect to the halopalladium residue. The subsequent syn elimination yields an alkene and a hydridopalladium halide. This process is, however, reversible, and therefore, the thermodynamically more stable (E)-alkene is generally obtained. Reductive elimination of HX from the hydridopalladium halide in the presence of a base regenerates the catalytically active Pd(0), which can reenter the catalytic cycle. The oxidative addition has frequently assumed to be the rate-determining step. 

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

The coupling of terminal alkynes with aryl or alkenyl halides catalysed by palladium and a copper co-catalyst in a basic medium is known as the Sonogashira reaction. A Cu(I)-acetylide complex is formed in situ and transmetallates to the Pd(II) complex obtained after oxidative addition of the halide. Through a reductive elimination pathway the reaction delivers substituted alkynes as products. 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

Another general process involves the reaction of Pd(0) species with halides or sulfonates by oxidative addition, generating reactive intermediates having the organic group attached to Pd(II) by a ct bond. The oxidative addition reaction is very useful for aryl and alkenyl halides, but the products from saturated alkyl halides often decompose by (3-elimination. The a-bonded species formed by oxidative addition can react with alkenes and other unsaturated compounds to form new carbon-carbon bonds. The... 

Another important type of reactivity of palladium, namely oxidative addition to Pd(0), is the foundation for several methods of forming carbon-carbon bonds. Aryl126 and alkenyl127 halides react with alkenes in the presence of catalytic amounts of palladium to give net substitution of the halide by the alkenyl group. The reaction, known as the Heck reaction,128 is quite general and has been observed for simple alkenes, aryl-substituted alkenes, and substituted alkenes such as acrylate esters, vinyl ethers, and A-vinylamides.129... 

These reactions proceed with retention of double-bond configuration in both the boron derivative and the alkenyl halide. The oxidative addition by the alkenyl halide, transfer... 

The mechanism presumably involves initial oxidative addition of the alkenyl halide to the Cu(I) species and ensuing cyclization analogy for this type of process is provided by the Cu(I)-mediated reaction of phthalimide anions with alkenyl and aryl halides.40 The -isomer of 15 reacts in a different fashion to give an isothiazolidinone derivative, albeit in low yield. 

The catalytic cycle consists of the following basic reactions. In the first step (A) of the cycle, Pd species 29 undergoes oxidative addition of an alkenyl or aryl halide 30. The result is a a-alkonyl or a-aryl palladium complex 31. In the second step, alkene 32 coordinates with Pd(II) compound 31 This is followed by syn insertion (B) of the double bond into the alkenyl or aryl palladium bond... 

The Heck reaction involves the coupling of an organopalladium species formed by oxidative addition to an alkene followed by /S-hydride elimination. The product is an alkene in which a vinyl hydrogen on the original alkene is replaced by die organic group on palladium. Thus aryl and alkenyl halides can be coupled to alkenes. 

The Heck reaction was discovered in the early 1970s and is extremely useful for rapidly assembling carbon skeletons. This reaction is unique to palladium A great deal of information is known about the reaction. For example, the success of the reaction depends on each of the three steps involved. Electron-donating groups decrease the reactivity of alkenyl halides and triflates toward Pd(0), whereas electron-withdrawing group increase the rate of oxidative addition. In cases where Pd(II) salts are used, it is assumed that they are converted to Pd(0) by some redox process. 

Stille coupling was also developed in tlie early 1980s and is similar to Suzuki coupling in its sequence. It is used to couple aryl or vinyl halides or triflates with organotin compounds via oxidative addition, transmetallation, and reductive elimination. The oxidative addition reaction has tlie same requirements and preferences as discussed earlier for tlie Heck and Suzuki reactions. The reductive elimination results in formation of tlie new carbon-carbon bond. The main difference is that tlie transmetallation reaction uses an organotin compound and occurs readily without the need for an oxygen base. Aryl, alkenyl, and alkyl stannanes are readily available. Usually only one of tlie groups on tin enters into... 

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