Alkene derivatives aminopalladation

The Hegedus indole synthesis involves one of the earlier (formal) examples of olefin hydroamination. An ortho-vinyl or ortho-nllyl aniline derivative 1 is treated with palladium(II) to deliver an intermediate resulting from alkene aminopalladation. Subsequent reduction and/or isomerization steps then provide the indoline or indole unit 2, respectively. 

Two recent reports have described Pd"-catalyzed carboamination reactions involving two alkenes that afford pyrrolidine products. Building on early work by Oshima that employed stoichiometric amounts of palladium [44], Stahl has developed an inter-molecular Pd-catalyzed coupling of N-allylsulfonamide derivatives with enol ethers or styrene derivatives that affords substituted pyrrolidines in high yields with moderate diastereoselectivity [45]. For example, treatment of 44 with styrene in the presence of Pd" and Cu" co-catalysts, with methyl acrylate added for catalyst stability, provided 45 in 97% yield with 1.9 1 dr (Eq. (1.21)). This reaction proceeds through intermolecular aminopalladation of styrene to afford 46. Intramolecular carbopalla-dation then provides intermediate 47, and subsequent P-hydride elimination yields product 45. 

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. 

One of the most common methods employed for the generation of allylpalladium complexes involves oxidative addition of allylic electrophiles to Pd . This transformation has been explored by several groups, and has been the topic of recent reviews [69]. A representative example of this process was demonstrated in a recent total synthesis of (+ )-Biotin [70]. The key step in the synthesis was an intramolecular amination of 89, which provided bicydic urea derivative 90 in 77% yield (Eq. (1.40)). In contrast to the Pd"-catalyzed reactions of allylic acetates bearing pendant amines described above (Eq. (1.10)), which proceed via alkene aminopalladation, Pd -catalyzed reactions of these substrates occur via initial oxidative addition of the allylic acetate to provide an intermediate Jt-allylpalladium complex (e.g., 91). This intermediate is then captured by the pendant nudeophile (e.g., 91 to 90) in a formal reductive elimination process to generate the product and regenerate the Pd catalyst. Both the oxidative addition and the reductive elimination steps occur with inversion... 

This same two-step diamination process was employed in the palladiuminternal alkenes (Scheme 4.11) [35]. Here, 2,2 -diamino stilbene derivatives were converted into the corresponding diamines with complete diaster-eoselectivity (Eq. (4.25)). This stereochemical outcome was rationalized by the assumption of an initial amide-palladium interaction, which is unproductive regarding a possible syn-aminopalladation as it would generate an azetidine intermediate. Instead, trans-aminopalladation takes place, followed by rapid oxidation to an q -coordinated benzylic palladium(IV) with preservation of the relative stereochemistry. Anti-C-N-bond formation then displaces palladium(II) to close the catalytic cycle and to displace the C2-symmetric diamine product. 

The oxidative addition reactions to alkenes promoted or catalyzed by PdCl2(CH3CN)2 have been classified based on the nature of the attacking species. Oxygen nucleophiles such as water, alcohols and carboxylic acids undergo oxypalladation, while ammonia, amines and their derivatives are typical nucleophiles for aminopalladation. Carbopalladation with active methylene compounds is also discussed The palladium-catalyzed intramolecular hetero- and carbopalladation of olefins is extensively used as the ring-forming step in the synthesis of a variety of heterocyclic and carbocyclic systems, and representative examples are provided. 

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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