Hydridopalladium

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-... 

Scheme 13. Trost s hydridopalladium acetate catalyzed cycloisomerization chemistry.

Scheme 14. Trost s approach to [3.3.3]propellane 67 by hydridopalladium acetate-catalyzed sequential cycloisomerization.

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. 

Morpholine also gives the allyhc amine in high yield. The reaction is thought to involve a known hydridopaUadium-catalyzed isomerization of alkynes to aUenes followed by reaction of the latter with the hydridopalladium complex to give 1-phenyl-substituted q -allylpalladium complexes. These complexes react with amines affording the allylic amines. Primary amines give the diallylic amines. An intramolecular version has been developed for the synthesis of 2-(2-phenyl)-pyrroUdines and -piperidines [319]. 

Many palladium-catalyzed reactions are initiated by the reaction of a palladium(O) complex with an acidic derivative.367 The catalytic cycle is considered to be induced by a hydridopalladium complex. When the acidic derivatives are strong acids (e.g., HBF4, HC1, CF3C02H, HOTs), the hydridopalladium formation may be regarded as the protonation of basic Pd° to afford complexes HPdL3 +368-374 or IIPdL2.S +,375 in which S = solvent (see Equation (1)) ... 

An electron-rich metal can deprotonate the dicarbonyl derivative, affording the hydridopalladium intermediate 23, which can undergo a Tr-allyl 24 formation through diene insertion (which can be assimilated to a hydridopalladation of olefin) (Scheme 7). The attack of the enolate to the -jr-allyl species occurs with good enantioselectivity in the presence of the chiral ligand. The final product 21 is released and the palladium(O) complex 22 is regenerated. 

In analogy to the mechanism of the palladium-catalyzed enyne cyclization, it is postulated that exposure of palladium(O) to acetic acid promotes in situ generation of hydridopalladium acetate LnPd"(H)(OAc). Alkyne hydrometallation affords the vinylpalladium complex A-10, which upon r-carbopalladation of the appendant alkyne provides intermediate B-7. Silane-mediated cleavage of carbon-palladium bond liberates the cyclized product along palladium(O), which reacts with acetic acid to regenerate hydridopalladium acetate to close the cycle (Scheme 33). 

Insertion of the alkyne into the Pd-H bond is the first step in the proposed catalytic cycle (Scheme 8), followed by insertion of the alkene and /3-hydride elimination to yield either the 1,4-diene (Alder-ene) or 1,3-diene product. The results of a deuterium-labeling experiment performed by Trost et al.46 support this mechanism. 1H NMR studies revealed 13% deuterium incorporation in the place of Ha, presumably due to exchange of the acetylenic proton, and 32% deuterium incorporation in the place of Hb (Scheme 9). An alternative Pd(n)-Pd(iv) mechanism involving palladocycle 47 (Scheme 10) has been suggested for Alder-ene processes not involving a hydridopalladium species.47 While the palladium acetate and hydridopalladium acetate systems both lead to comparable products, support for the existence of a unique mechanism for each catalyst is derived from the observation that in some cases the efficacies of the catalysts differ dramatically.46... 

Dienones. Alkynones, which are readily available by addition of lithium acet-ylides to N-methyl-N-methoxyamides (11,202), isomerize to dienones when treated with Pd(OAc)2 in combination with a phosphine, particularly dppb. The actual catalyst is probably a hydridopalladium acetate.1... 

In the same research group the cationic hydridopalladium complex [Pd(H)(H20)(PCy3)2] [BF4] has been shown to catalyze the hydroxycarbony-lation of triple bonds. As a representative example the dehydration occurring to give the dienoic acid is displayed in Scheme 3 [35]. The same cationic complex is able to activate a carbon oxygen bond in a-allenic alcohols to provide dienoic acids but with the COOH group in the branched position (Scheme 3) [36]. 

Scheme 9 Proposed hydridopalladium route for alcoxycarbonylation reaction...

The prototype of this sequence has been discovered by Brewis and Hughes as early as in 1965 in the carbonylation of 1,5-diene (Equation (26)), " though in this case the process is initiated not by oxidative addition of Pd(0) to C-X bond, but by the addition of hydridopalladium complex to double bond. ... 

As expected, the reaction of complexed III proceeds with high stereoselectivity. Oxypalladation followed by elimination of a hydride of palladium should yield HPd(OAc) ((CH3)8CC(OAc)=CH2). Oxidation of the hydridopalladium species to a hydroperoxide is an attractive possibility as the first step in catalyst regeneration. For n-hexenes which have... 

Olefinic compounds will often insert into carbon-transition metal bonds as CO does, and this reaction is an important step in many catalytic syntheses. When this step is combined with an oxidative addition of an organic halide to a palladium(O) complex in the presence of a base, a very useful, catalytic olefinic substitution reaction results (26-29). The oxidative addition produces an organopalladium(II) halide, which then adds 1,2 to the olefinic reactant (insertion reaction). The adduct is unstable if there are hydrogens beta to the palladium group and elimination of a hydridopalladium salt occurs, forming a substituted olefinic product. The hydridopalladium salt then reforms the... 

The elimination of the hydridopalladium group to the allylic position causes the formation of 3-substituted carbonyl compounds when allylic alcohols are reacted with organic halides (39). For example, when iodobenzene is reacted with methallyl alcohol, 2-methyl-3-phenylpropanal was formed in 91% yield along with 4% of 2-methyl-2-phenylpropanal ... 

We do not know if the vinylic alcohol is actually an intermediate or whether a hydride-71 complex of it rearranges directly to the aldehyde as probably happens in the palladium-catalyzed oxidation of ethylene to acetaldehyde. The formation of 4% 2-methyl-2-phenylpropanal is unexpected. This product must arise from a reversed addition of the phenylpalladium group followed by a hydrogen transfer from the hydroxyl-bearing carbon to the palladium, followed by reductive elimination of a hydridopalladium group. An alkyoxypalladium intermediate has been proposed (39). 

Vinylation of dienes in the presence of piperidine or morpholine yields aminodienes as major products. Sometimes trienes are minor products. The reaction is believed to proceed by way of a ir-allylpal-ladium complex formed by addition of the vinylpalladium halide to the least-substituted diene double bond. Nucleophilic attack of the amine upon the ir-allylic complex gives the aminodienes, while hydridopalladium halide elimination yields trienes (Scheme 6).97... 

Additions to functionalized three-carbon olefins have been studied extensively. We have used methyl acrylate as a standard olefin since it always reacts only at the terminal carbon and the a,/3-double bond in the product is always trans. The stereospecificity of its reactions with vinylic halides varies with structure. The simple 1-halo-l-alkenes with methyl acrylate under normal conditions give mixtures of E,Z- and E,E-dienoates. The reaction is more selective with the bromides than with the iodides and the stereoselectivity increases with increasing triphenylphosphine concentration. This occurs because the excess phosphine displaces the hydridopalladium halide group from the diene 7r-complex before readdition to form the ir-allylic species occurs (see Equation 6). The disubstituted vinylic bromides react stereospecifically with methyl acrylate (4). 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

An interesting synthetic route to 2,3-substituted indenones 205 was discovered by the annulation of alkynes with o-iodobenzaldehyde (203) [86], In this reaction, the CH bond of the aldehyde may oxidatively add to Pd(0) to generate the hydridopalladium 204, which produces indenones 205 by reductive elimination. 

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