Aminopalladation reaction mechanisms

Hegedus proposed that the mechanism of this transformation proceeds through a Wacker-type reaction mechanism that is promoted by Pd(II). As shown below, coordination of the olefin to Pd(II) results in precipitate 121, which upon treatment with Et,N undergoes intramolecular trany-aminopalladation to afford intermediate 122. As expected, the nitrogen atom attack occurs in a 5-exo-trig fashion to afford 123. [l-Hydride elimination of 123 gives rise to exocyclic olefin 124, which rearranges to indole 120. The final step of this mechanism leads to the formation of catalytically inactive Pd(0). However, addition of oxidants such as benzoquinone allows for catalytic turnover. 

The Pd(ll)-catalyzed exchange of allylic groups as illustrated in Eq. (107) (Atkins et al., 1970) could be regarded as a nucleophilic attack on an incipient allyl carbonium ion, but the reaction mechanism probably involves a simple aminopalladation, followed by dehydroxypalladation (Henry, 1973). 

Shi et al. reported a unique indole synthesis from simple anilines without the aid of any directing group on the nitrogen [34]. Thus, aniline itself (85) couples with dimethyl acetylenedicarboxylate (2b) in the presence of Pd(OAc)2 under O2 to produce indole 86 (Scheme 25.41). A reaction mechanism involving initial hydroam-ination/palladation or aminopalladation of 2b and subsequent cyclopalladation has been proposed. 

A Pd(II)-catalyzed sequential cyclization-coupling reaction of allenyl N-tosylcar-bamates and acrolein has been developed (Scheme 16.97) [103]. The proposed mechanism involves intramolecular aminopalladation of an allene, followed by insertion of acrolein and carbon-Pd bond protonolysis. 

Yang has reported a related tandem cydization for the synthesis of pyrroloindoline derivatives that also proceeds though a mechanism involving alkene aminopalladation followed by carbopalladation of a second alkene [46]. As shown below, the 2-allylaniline derivative 48 was converted to 49 in 95% yield through treatment with a catalyst composed of Pd(OAc)2 and pyridine (Eq. (1.22)). Use of (-)-sparteine as a ligand in this reaction provided 49 with up to 91% ee. 

The mechanism of this reaction involves anfi-aminopalladation of the alkene to afford 163, which undergoes CO insertion to form 164. Capture of the acylpalladium intermediate 164 with methanol (formed in situ from trimethyl orthoacetate) gives the heterocyclic product. 

The stereochemistry of aminopalladation, as is involved in the initial step of the aza-Wacker reaction, is still a subject of ongoing research. A particularly extensive mechanistic study by Stahl and Liu uncovered the stereochemical aspects of intramolecular aminopalladation under Wacker-type conditions. Here, the selectively deuterated compound 46 was used to probe the overall mechanism through product evaluation. It turned out that, for almost all common catalyst combinations, the reaction led to two deuterated alkenes, which were identified as product 47 and its regioisomer. As the final step of 3-hydride elimination must be a syn-selective... 

In 2002, Liu and Lu disclosed a pd(II)-catalyzed cascade cyclization-coupUng reaction of allenyl N-tosylcarbamates 339 and acrolein, furnishing aldehyde-functionalized 2-oxazolidinones 340 in one step with high regioselectivity [116] (Scheme 6.89). A mechanism involving aminopalladation of alllene, followed by insertion of alkene and C—Pd bond protonolysis instead of p-hydride elimination, is proposed by the authors. 

Carboamination reactions have been classified into two types depending on the mode of reaction in the first case, the reaction proceeds via the formation of 1) an outersphere aminopalladation complex like the PdX2-aIkene complex via oxidative addition, which in the next step reacts with the amine and an external electrophile to afford the cyclized product. In a type II mechanism, the reaction takes place through the formation of 2) an innersphere complex where the Pd(0) catalyst forms the complex with an electrophile, e.g., aryl haUde via oxidative addition. Then, it reacts with the amine to form the Pd(Ar) amide complex, which eventually gets converted into the product via the alkene insertion and C—C bond-forming reductive elimination. Here, it is noteworthy that, in a type I reaction, the addition across the olefinic bond took place in rarri-fashion, whereas the 5y -addition mode was observed in case of the type It mechanism (Scheme 40.1). ... 

Reactions via Pd(II)-Alkene Complex In 1980, Hegedus et al. reported on the synthesis of indole derivatives via a Pd-catalyzed intramolecular amination of alkenes in the presence of carbon monoxide (Scheme 40.2). This reaction follows the outersphere aminopalladation mechanism. This report can be considered the first example of today s carboamination reaction although the authors did... 

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