Hydropalladation intermediates

Methylenecyclopropanes were particular substrates object of several studies by Yamamoto [91]. The interest in the addition of alcohols was due to the formation of allyl ethers with high regioselectivity, through the distal bond cyclopropane cleavage of the hydropalladate intermediate as shown in Scheme 44. Combination of Pd... 

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 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.

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). 

A useful synthesis of ( )-j -ethoxycarbonylvinylsilanes by palladium-catalyzed regio- and stereospecific hydroesterification (EtOH -I- CO) (or carboethoxylation) of trimethylsilylacetylenes has been reported recently [210]. Alkoxycarbonyl or carbonyl functionalization of vinylsilanes are useful synthetic intermediates [211, 212]. The use of PdCl2(dppf) as a catalyst (with SnCl2 2 H2O as cocatalyst) is found to be superior and gives excellent yields. A key step in the reaction is thought to involve hydropalladation to give 60 or 61. The preference for 60 to 61 is understood... 

Due to the higher reactivity of the allene moiety toward hydropalladation in 1,6-allenynes, the reaction may proceed via a hydropalladation of the allene moiety of 146 affording a vinylic palladium intermediate 147. Subsequent intramolecular carbopalladation of the C-C triple bond moiety would lead to the 1,3-dienyl palladium formate 148. Releasing of CO2 and reductive elimination afford the final product 149 and Pd(0). Pd(0) would react with HCO2H to afford HC02PdH, which is the catalytically active species (Scheme 61) [36]. 

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. 

Reaction mode A (Scheme 16) has recently also been realized for the Pd-catalyzed hy-drofurylation of alkylidenecyclopropanes 63 in which a hydropalladation is the initial step (Scheme 17). Mechanistic investigations of this reaction using a labeled 2-alkyl-5-deuteriofuran demonstrated this transformation to really proceed via intermediates 66 and 67 rather than by a direct insertion of a furylpalladium species into the distal bond of the methylenecyclopropane 63. The deuterium content at the methyne position of 65 was, however, only 44%. 

In the Pd-catalyzed hydrocarbonation of methylenecyclopropanes 68 with pronucleophiles of type 69 (Scheme 18), the direction of the initial hydropalladation depends craciaUy on the electron density distribution in the double bond of 68. Thus, a competition of the reactions along both pathways A and B can be observed. When R = alkyl or substituted alkyl, the reaction proceeds mainly via intermediates I and II furnishing the hydrocarbonation products 70 in good to very good yields. This type of reaction was performed both as an inter- as well as an intramolecular version. The reaction proceeded... 

Intramolecular carbopalladations usually are fast processes, which are terminated by de-hydropalladation unless the carbopalladation leads to an alkenyl- or neopentylpalladium intermediate, in which cases cascade carbopalladation sequences can be set off with other externally or internally available rr-systems. 

In this protocol, palladium hydride addition to the triple bond (i.e., hydropalladation) is invoked as the key step to explain the formation of the six-membered ring lactones, which would require isomerization about the olefin in order to occur. Addition of the palladium hydride across the triple bond leads to the ( )-olefin shown in Scheme 29, which can isomerize to the (Z)-olefin via an intermediate cationic vinylpalladium species. The cyclization then can easily proceed via the (Z)-olefinic alcohol. 

Brewis and Hughes reported in 1966 what appears to be the first example of a Type I Ac-Pd process shown in Scheme 9. Although unclear, the initial organopalladium intermediate was thought to have been formed via hydropalladation. This reaction had... 

Insertions of alkynes into palladium-hydride complexes have been reported to take place as part of catalytic cycles, resulting in circumstantial yet credible evidence for the occurrence of alkenylpalladium complexes. The first example of palladium-catalyzed hydroarylation of alkynes with organoboronic acids B(OH)2R has been given. The mechanistic interpretation based on labeling studies involves hydropalladation of the alkyne to give an intermediate alkenylpalladium(ii) species that reacts with the organoboronic acid (Scheme 11). Similar direct coupling reactions... 

Later on, the reactivity was extended to electron-rich alkoxyallenyl tert-cyclobutanols [62, 63], With this substrate class, hydropalladation of the allene generates the required a -aUylpalladium intermediate 114 to trigger the 1,2-shift (Scheme 24). Again, ring expanded cyclopentanones 115 were obtained in high yields, enantioselectivity, and diastereoselectivity with L13. A critical point of the initial hydropalladation is careful pH control. 

A similar reaction of A(-alkoxycarbohgl-8-azabicyclo-[5.1.0]oct-3-ene with a stoicbiometric amount of Pd(PhCN)2Cl2 was also observed (eq 146). However, if the reaction was conducted in the absence of any reagent, it afforded the ring-opening-azapalladation-repeated -H eUmination-hydropalladation-/3-Cl elimination product (eq 147). In the presence of CO and MeOH, the product formed via carbonylation of the azapalladation intermediate would be produced (eq 148). In the presence of NaBH4, reduction was observed (eq 149). ... 

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