Hydropalladation

Another useful class of palladium-catalyzed cycloisomerizations is based on the general mechanistic pathway shown in Scheme 13. In this chemistry, a hydridopalladium acetate complex is regarded as the catalytically active species.27b-29 According to this pathway, coordination of a generic enyne such as 59 to the palladium metal center facilitates a hydropalladation reaction to give intermediate 60. With a pendant alkene, 60 can then participate in a ring-form-... 

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. 

Hydrosilylation of o-allylstyrene (82) with trichlorosilane in the presence of 0.3mol% of a palladium catalyst bearing triphenylphosphine has been found to produce a mixture of indane (83) and the open-chain products (84) and (85) (Scheme 11). The reaction of styrene with trichlorosilane gave a quantitative yield of 1-phenyl-l-(trichlorosilyl)ethane whereas allylbenzene did not give silylation products under the same reaction conditions. These results show that the hydropalladation process is operative in the hydrosilylation of styrene derivatives with trichlorosilane catalysed by palladium-phosphine complexes." ... 

The reaction between aqueous K2PdCl4 and CMe2(OH)CsCCsCCMe2(OH) (L) has been reported to give the palladium(I) complex PdCl(L), which exchanges L for X with salts MX (M = alkali metal, X = SCN, Br, I) and adds py to give PdCl(L)(py). However, it must be said that the dark brown to black solids so formed are not fully characterized by contemporary standards. It was assumed that hydropalladation of one C C triple bond has occurred. ... 

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. 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

In a formally similar reaction an alkene and an alkyne moiety were coupled in the presence of a palladium catalyst in formic acid. The reaction cascade in this case starts by the hydropalladation of the triple bond, which is followed by a Heck-type carbon-carbon bond formation. Running the... 

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.

The above-mentioned cyclization starts with the insertion of alkynes to the Pd—H bond to generate alkenylpalladium species (hydropalladation). Polycyclization of... 

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... 

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). 

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

Hydrocarbonation of enyne proceeds via hydropalladation of enyne with 16, which affords the exo methylene Jt-allylpalladium complex. Reductive elimination would lead to formation of 5. 

In the hydrocarbonation of alkynes (Scheme4), the hydropalladation-elimination of HPdOAc 19, generated from Pd(0) and acetic acid, to internal alkynes 6 produces allenes 21 and the active catalyst (HPdOAc) (catalytic cycle I). The second hydropalla-... 

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). 

Pd-catalyzed C-H transformation at nitriles to methylenecydopropanes 8 affords the terminal 9 and internal alkenes 10, either exclusively or as a mixture of both (Scheme 2, Eq. 4) [9]. The selectivity of product formation depends on the mode of hydropalladation of the carbon-carbon double bond of the methylene-cyclopropane and ring opening. Ring opening normally occurs at the distal bond. Also, the mode of ring opening of methylenecydopropane depends on the chain length of the substituent at the exomethylene carbon. In the addition of malononi-trile lb to 8b, both monoalkylation and dialkylation products are obtained as a 1 1 mixture (Eq. 10). 

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