Hydropalladation mechanism

Figure 1.11 provides an example of H NMR monitoring in the Pd-catalyzed cy-doisomerization of dimethyl diallyl malonate, 39 [28]. The kinetic profile reveals a pronounced induction period after which the exocydic alkene 40a is formed predominantly as the kinetic product. A hydropalladation mechanism was proposed on the basis of NMR experiments, and the transient spedes 41, formed by allylpalla-dation of the coordinated diene, could be detected and identified with the help of and labeling. The hydride Pd catalyst, 42, would be generated from 41 by water-promoted P-hydride elimination. The observed induction period is assodated with the formation of the Pd-hydride 42. 

A mechanistic rationale for the Pd-catalyzed addition of a C-H bond at nitriles to allenes is outlined in Scheme 3. The oxidative insertion of Pd(0) into the C-H bond of nitrile 1 produces the Pd(II) hydride species 16 (or alternatively a tautomeric structure E E2C=C=N PdH Ln may be more suitable, where E = H, alkyl, aryl and/or EWG). Carbopalladation of the allene 2 would afford the alkenylpalladium complex 17 (carbopalladation mechanism), which would undergo reductive coupling to give the addition product 3 and regenerates Pd(0) species. As an alternative mechanism, it may be considered that the hydropalladation of allenes with the Pd(II) intermediate 16 gives the jr-allylpalladium complex 18 which undergoes reductive coupling to afford the adduct 3 and a Pd(0) species (hydropalladation mechanism). 

The Pd-catalyzed hydrocarbonations of methyleneaziridines 14 do not proceed through the formation of a Jt-allylpalladium intermediates, instead via a chelation effect. The hydropalladation of methyleneaziridines with the Pd(II) hydride species 16, followed by reductive elimination gives the non-ring-opened products 15. It is noteworthy to mention that the palladium-catalyzed intermolecular or intramolecular addition of nitriles to carbon-carbon multiple bonds can be explained by the hydropalladation mechanism, except for the intramolecular addition to the C=C triple bond of alkynes (vide infra). 

In this section, Pd(0)-catalyzed reactions of allenes with nucleophiles are treated, which are clearly different mechanistically from the reactions explained in the above. Attack of nucleophiles may occur at C-1, C-2, and C-3 carbons of the allenes 63. Among them, attack at C-3 to give 64 is predominant. Most importantly, reactions of allenes with pronucleophiles start by the oxidative addition of pronucleophiles to Pd(0) to generate H-Pd-Nu 65. The formation of 64 by hydro-carbonation can be explained in two ways in the case where Nu-H is the carbon pronucleophile. As one possibility, hydropalladation of one of the two double bonds occurs to afford the terminal palladium intermediate 66, which is stabilized by the formation of 7r-allyl complex 67, and reductive elimination provides the C-3 adduct 68. Another possibility is carbopalladation to generate 69, and subsequent reductive elimination provides 68. Of these two possibilities, the hydropalladation mechanism is preferable. 

The Pd°-catalyzed transformation of enediynes represents a highly efficient and effective approach for the synthesis of polycyclic compounds, with different ring sizes being obtained by a variation of the tether [129]. In this respect, reaction of 6/1-270 led to the tricyclic product 6/1-271 as a single diastereomer. The initial step is a chemoselective hydropalladation of the propargylic ester moiety in 6/1-270 to give an alkenyl-Pd-species, according to the mechanism depicted in Scheme 6.71. A hexatriene is formed as a byproduct. 

The formation of a six-membered ring is also feasible but is more limited, and the reaction is found to be more sensitive to the reaction conditions (Scheme 51). The difficulty for forming cyclohexanes is ascribed to the poorer ability of 1,7-enynes to function as bidentate ligands. This problem can be partially circumvented by introducing an alkene moiety (206 vs. 207) or a substituent that can coordinate to the metal, such as a free carboxylic acid, although in this case, the actual mechanism involves hydropalladation as the first step (see Section 10.07.4.1.3.(i).). 

The mechanism of this reaction was considered on the basis of hydropalladation (Scheme 14). To minimize steric repulsions, the palladium hydride complex approaches the C=CH2 moiety of the allene in the anti-Markovnikov mode from the opposite side of the substituent. This addition gives a 7t—allyl palladium complex with the (Z)-configuration,18 which is converted to the (Z)-product by C-P bond formation, with regeneration of the Pd(0) catalyst. 

Scheme 12.11 Modification of mechanism IV to allow for the generation of either 11 or 12 with a type B catalyst, depending on the propensity of intermediate 15 for dissociation or hydropalladation to give 16.

Pd(PPh3)4-catalysed isomerization of methylenecyclopropanes in acetic acid proceeds smoothly at 1-substituted or 1,1-disubstituted dienes (Scheme 90). A plausible mechanism is hydropalladation and /3-carbon-Pd elimination followed by /3-hydride elimination, established from a deuterium labelling experiment.133... 

Scheme 3. C-H transformation to allenes hydropalladation or carbopalladation mechanism.

As p-hydride elimination is reversible, hydropalladation with the opposite regiochemistry provides a mechanism for forming regioisomers of the alkene. This allows the most stable alkene that is accessible by the hydropalladation-dehydropalladation sequence to dominate. The only restriction is that all of these processes are syn. The migration can be prevented by the addition of bases like silver carbonate, which effectively removes the hydrogen halide from the palladium complex as soon as it is formed. This synthesis of a complex trans dihydrofuran involves the Heck reaction followed by alkene isomerization and then a Heck reaction without migration to preserve the stereochemistry. 

Trost and co-workers have made great strides in developing the palladium-catalyzed cycloisomerization of enynes into a powerful ring-forming method [39]. In most cases, the intimate details of these reactions are unknown. They are considered here, since a Heck cyclization is a potential step of one possible mechanistic sequence [40]. Two plausible mechanisms for palladium-catalyzed cycloisomerization of enynes are depicted in Scheme 6-17. In the Heck pathway (101 102 103104), hydropalladation of the alkyne is... 

Research on the mechanism of the Pd(II)-catalyzed ene reaction points to a hydropalladation cycle shown in Scheme 12.27, which first involves compl-exation of Pd to both n ligands of the substrate to yield 82 (step a). Migratory 1,2-insertion of the alkyne into the Pd-H bond provides 83 (step b), and then 1,2-insertion of the rf-coordinated double bond occurs to yield 84 (step c). Finally, step d is -elimination, which yields two possible regioisomers (85 and 86). 

As an extension of hydrosilylation of alkenes, cyclization-hydrosilylation of 1,6-dienes occurs by the reaction with HSiRs [23]. The cationic complex 37, generated in situ from (phen)Pd(Me)Cl and NaBAr4, is an active catalyst, catalyzing the reaction of dimethyl diallylmalonate (36) with HSiCl3 to give the disubstituted cyclopentane 38 with 98% trans selectivity in 92% yield [24]. A mechanism different from that of usual hydrosilylation, which postulates formation of H-Pd-SiR3 and hydropalladation of alkene, was proposed by Widenhoefer... 

Hydropalladation and carbopalladation can proceed very readily with a variety of alkenes and alkynes, and they share some common critical features. Thus, they generally involve sttict syn addition of H— Pd and C— Pd bonds, respectively. These features are in agreement with a concerted mechanism involving interaction of an empty orbital of Pd with a TT-bond of alkenes or alkynes and that of H— Pd or C—Pd <7-bond with a 7r -orbital, as shown in Scheme 8. It should be noted that the overall synergistic bonding schane for hydropalladation or carbopalladation is very closely related to the Dewar-Chatt-Dun-canson (DCD) model " for Tr-complexation. In the schemes for hydropalladation and carbopalladation, the nonbonding Pd d orbital of the DCD model is substituted with a H— Pd and C—Pd <7-orbital, respectively. In all of these concerted processes, the presence or ready availability of a Pd empty orbital is critically important. 

Stereochemistry. There are ample experimental indications that both hydropalladation (pattern 5) and carbopalladation (pattern 8) as well as their microscopic reversals (patterns 15 and 18) are, at least in the great majority of cases, strict syn addition processes, as predicted by the concerted mechanism shown in Scheme 8. In the hydropalladation and carobpalladation reactions of alkynes, the stereochemical course of the reactions is readily seen and unmistakable. However, clear-cut and explicit demonstration of the... 

Various metal-metal bonded compounds containing relatively electronegative metals, such as Si, Ge, Sn, B, Al, and Zn, can undergo Pd-catalyzed metallometallation, which mostly involves yn-addition to alkynes. One plausible mechanistic scheme involves (i) oxidative addition of metal-metal bonded compounds to Pd, (ii) metallopalladation (pattern 6) leading to yn-addition of metal-Pd bonds, and (iii) reductive elimination (Scheme 12). As such, the overall mechanism resembles that of Pd-catalyzed hydrogenation or hydrosilation, and the critical metallopalladation step must be mechanistically closely related to those of hydropalladation and carbopalladation. These reactions are discussed in detail in Sect. Vn.5. 

Addition of CO to C=C and C=C bonds provides an alternative approach to lactones distinct from that of C—X and C—M carbonylation [6, 24]. In particular, hydrocarbonylation involves the formation of new C—H and C—C bonds (Scheme 2.12). Pd-catalyzed transformations of this type proceed through either hydropalladative or carbopalladative pathways [6]. In the carbopalladative mechanism, a Pd alkoxide undergoes carbonylation, yielding an acylpalladium species. Subsequent insertion into the C=C or C=C bond generates the desired lactone. Hydropalladation, on the other hand, is favored under reducing or acidic conditions and occurs via Pd hydride addition to the unsaturation, followed by CO insertion, and reductive elimination. 

The ability of Pd to participate in both hydrometallation and dehydrometallation snggests that Pd and its complexes can serve as catalysts for isomerization of alkenes and alkynes via a series of hydropalladation-dehydropalladation, that is 1,2-H shift. On the other hand, Pd-induced aUylic rearrangement provides a mechanism whereby alkenes can iso-merize via 1,3-shift. In either of these processes, the crucial reqnirement is the presence or ready availability of an empty coordination site. As amply demonstrated throughout this Handbook, Pd is imminently capable of serving as the catalyst center for isomerization of alkenes and alkynes. 

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