Palladium-catalyzed allylic substitution mechanism

The generally accepted mechanism of palladium-catalyzed allylic substitutions is shown in Scheme 1. An allylic substrate 1, typically an acetate or a carbonate, reacts with the catalyst, which enters the catalytic cycle at the Pd(0) oxidation level. Both Pd(0) and Pd(II) complexes can be used as precatalysts, because Pd(II) is easily reduced in situ to the active Pd(0) form. Presumably, the reaction is initiated by formation of a Ji-complex which eliminates X to produce an (ri -allyl)palladium(II) complex. The product of this oxidative addition can... 

In the absence of nucleophiles, the intermediate allyl complexes are stable and can be isolated. This is an attractive, quite unique feature of palladium-catalyzed allylic substitutions, because in most catalytic processes it is difficult to isolate or even merely detect intermediates of the catalytic cycle. The vast amount of data on the structure and reactivity of (allyl)palladium complexes that is available, has led to valuable insights into the mechanism of allylic substitutions and the origin of enantioselection in reactions with chiral catalysts (see Sect. 7). 

Palladium-catalyzed allylic substitution reactions, known as Tsuji-Trost reactions, are a well-established method for carbon-carbon bond forming processes [48]. The generally accepted mechanism for this reaction involves the oxidative addition of the allylic substrate to Pd(0) to provide a Jt-allylpalladium complex. The subsequent reaction of the electrophilic 7t-allylpalladium complex with the nucleophile affords the substituted product and Pd(0), which is regenerated to start the catalytic cycle (Scheme 7.26). 

Scheme 5.20 Stereochemical course of the palladium-catalyzed allylic substitution. Inner-and outer-sphere mechanisms.

The generally accepted mechanism for Pd-catalyzed allylic substitution involves association of the palladium(0) catalyst to the substrate, and oxidative addition to provide a ir-aUyl complex. The equilibrium between the neutral 7r-allyl complex and the more reactive cationic 7r-allyl complex depends on the nature/concentration of phosphine Ugand. Nucleophilic addition to the ligand involves direct attack on the ligand when stabilized enolates are employed. After dissociation of the product, the palladium is able to continue in the next catalytic cycle (Scheme 2). In general, the reaction proceeds via a Pd(0)/Pd(II) shuttle, although a Pd(II)/Pd(IV) pathway is also possible. 

The mechanism of the Zn chloride-assisted, palladium-catalyzed reaction of allyl acetate (456) with carbonyl compounds (457) has been proposed [434]. The reaction involves electroreduction of a Pd(II) complex to a Pd(0) complex, oxidative addition of the allyl acetate to the Pd(0) complex, and Zn(II)/Pd(II) transmetallation leading to an allylzinc reagent, which would react with (457) to give homoallyl alcohols (458) and (459) (Scheme 157). Substituted -lactones are electrosynthesized by the Reformatsky reaction of ketones and ethyl a-bromobutyrate, using a sacrificial Zn anode in 35 92% yield [542]. The effect of cathode materials involving Zn, C, Pt, Ni, and so on, has been investigated for the electrochemical allylation of acetone [543]. 

Facing all the mechanism-related peculiarities of the thermally induced rearrangement it was consequential to try to shift the reaction toward one end of the mechanistic spectrum. The first steps in that direction were undertaken by Hiroi et ah in 1984 they reported on a palladium-catalyzed variant of the reaction [49]. With enantiomerically enriched sulfinates 61 (Scheme 16) they found a much faster reaction as compared to the uncatalyzed one, allowing a reduction of the reaction temperature down to - 78 °C ( ). The stereospecificity of the rearrangement depended heavily on the substitution pattern (between 28 and 92%) and was traced back to the intermediacy of a configurationally stable ri -jt-allylpalladium species whose configuration was influenced by the S centro chirality. Unfortunately, due to difficulties in the preparation of enantiomerically pure 2-alkenylsulfinates (see above), the ee values of the resulting allylic sulfones were quite low. 

The most important class of allylic substitutions are palladium-catalyzed reactions with so-called soft nucleophiles such as stabilized carbanions or amines, and with few exceptions, the enantioselective transformations discussed in this chapter belong to this category. The mechanism of these reactions has been firmly established and a detailed picture of the catalytic cycle can be drawn [1, 2,3,4,5,6,13,14,15]. The course of allylic substitutions catalyzed by metals other than palladium is less clear and information about the intermediates involved is scarce. 

Scheme 12.2 Mechanisms of the palladium-catalyzed nucleophilic allylic substitutions.

In addition to benzylations, palladium-catalyzed C-H allylation reactions have also been described, but they usually involve the electrophilic substitution of an electron-rich (hetero)arene with a 7t-allyl palladium complex and therefore deviate from the scope of this chapter [41, 42]. In contrast, the palladium/copper-catalyzed allylation of polyfluoroarenes with allyl carbonates (Scheme 19.27) has been reported to occur through a different mechanism [43]. Thus, base-induced cupration of the arene would give rise to intermediate 15 that was previously characterized by X-ray crystallography [44]. Attack of the in sitw-generated JT-allyl... 

Allyl chlorides can be employed in place of alkynes for the palladium-catalyzed [2-I-2-I-2] cycloaddition of arynes, as reported by Yamamoto et al. in 2000 [16]. Substituted allyl chlorides 40 reacted with aryne from 39 accompanying the elimination of HCl in the presence of a paUadium(0) catalyst and CsF to produce phenanthrenes 41 and 42 in good yields, although the regioselectivity was moderate (Scheme 6.13). A mechanism that has been proposed involves a cascade-type addition of -ir-allylpalladium complex onto two benzynes. In the presence of additional alkynes 44, three-component cycloaddition product 45 was obtained in good yields with complete regioselectivity (Scheme 6.14). 

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