Alkylation reactions allylic, palladium catalyzed

The great importance of nonproteinogenic amino acids including a-substituted derivatives led to numerous investigations of modified amino acid enolates as nucleophiles in both classical alkylation or Mannich reactions and palladium-catalyzed allylic alkylations. 

Chiral phosphinous amides have been found to act as catalysts in enantio-selective allylic alkylation. Horoi has reported that the palladium-catalyzed reaction of ( )-l,3-diphenyl-2-propenyl acetate with the sodium enolate of dimethyl malonate in the presence of [PdCl(7i-allyl)]2 and the chiral ligands 45 gave 46 in 51-94% yields and up to 97% ee (Scheme 38). It is notorious that when the reaction is carried out with the chiral phosphinous amide (S)-45a, the product is also of (S) configuration, whereas by using (R)-45b the enantiomeric (R) product is obtained [165]. 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Allylic carbonates are better electrophiles than allylic acetates for the palladium-catalyzed allylic alkylation.77 Reaction of Eq. 5.54 shows the selective allylic alkylation of a-nitro ester with allylic carbonates without affecting allylic acetates.78... 

Allyl acetates are more commonly used as electrophiles for the palladium-catalyzed allylic alkylation than allylic nitro compounds.20 However, the reaction of allylic nitro compounds has found wider applications. Allylic nitro compounds are readily available by nitration of alkenes. The regio- and stereoselective introduction of electrophiles and nucleophiles into alkenes is possible as outlined in Eq. 7.19. In fact, this strategy is applied to the synthesis of terpenoids.21... 

Aliphatic aldoximes and ketoximes undergo palladium-catalyzed O- and N-alkylation by butadiene in reactions that presumably occur via jr-allyl... 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

Enantio- and diastereoselective syntheses of a variety of heterocycles were accomplished by combining the ruthenium-catalyzed Alder-ene reaction with a palladium-catalyzed asymmetric allylic alkylation (AAA) (Scheme 7). For the AAA, y>-nitrophenol was found to function as a suitable leaving group and yet was stable to the Alder-ene conditions. Extensive solvent studies were performed to determine the best conditions for the one-pot procedure. 

Thus, the sole remaining stereocenter after epoxide opening controls the formation of three other stereocenters. It should be noted that the synthesis of enantiomerically pure substrates via palladium-catalyzed allylic alkylation [80] is possible and offers an access to the products in enantiomerically pure form. This possibility and the diastereoconvergent course of our reaction are extremely attractive for the synthesis of complex molecules. 

A single reaction has been described in which a palladium-catalyzed reaction was employed to form an alkyne [45], Thus, attempted alkylation of carbonate 145 with dimethyl malonate in the presence of Pd(PPh3)4 gave a mixture of enyne 87 and the alkylation product 86 in a 15 1 ratio (Scheme 14.37). Methoxide caused an elimination in (jT-allyl)palladium intermediate 146, which is apparently faster under these conditions than a reaction with the nucleophile (cf. Eq. 14.9). The synthetic importance of this process seems to be limited. 

The regioselectivity in palladium-catalyzed alkylations has been attributed to the dynamic behavior of trihapto pentadienyl metal complexes60. For example, competing electronic and steric effects influence product formation in dienyl epoxides, but in palladium-catalyzed reactions steric factors were often found to be more important. Thus, alkylation of dienyl epoxide 76 with bulky nucleophiles such as bis(benzenesulfonyl)me-thane in the presence of (Ph3P)4Pd occurred exclusively at the terminal carbon of the dienyl system producing allyl alcohol 77 (equation 39). However, the steric factors could be overcome by electronic effects when one of the terminal vinylic protons was replaced with an electron-withdrawing group. Thus, alkylation of dienyl epoxide 78 affords homoal-lylic alcohol 79 as the major product (equation 40). 

The first iridium catalysts for allylic substitution were published in 1997. Takeuchi showed that the combination of [fr(COD)Cl]2 and triphenylphosphite catalyzes the addition of malonate nucleophiles to the substituted terminus of t -allyliridium intermediates that are generated from allylic acetates. This selectivity for attack at the more substituted terminus gives rise to the branched allylic alkylation products (Fig. 4), rather than the linear products that had been formed by palladium-catalyzed allylic substitution reactions at that time [7]. The initial scope of iridium-catalyzed allylic substitution was also restricted to stabilized enolate nucleophiles, but it was quickly expanded to a wide range of other nucleophiles. 

For further details of this reaction, the reader is referred to Chapter 9. The catalytic allylation with nucleophiles via the formation of Ti-allyl metal intermediates has produced synthetically useful compounds, with the palladium-catalyzed reactions being known as Tsuji-Trost reactions [31]. The reactivity of Ti-allyl-iridium complexes has been widely studied [32] for example, in 1997, Takeuchi idenhfied a [lrCl(cod)]2 catalyst which, when combined with P(OPh)3, promoted the allylic alkylation of allylic esters 74 with sodium diethyl malonate 75 to give branched... 

By 1984, the palladium-catalyzed aUyhc alkylation reaction had been extensively studied as a method for carbon-carbon bond formation, whereas the synthetic utility of other metal catalysts was largely unexplored [1, 2]. Hence, prior to this period rhodium s abihty to catalyze this transformation was cited in only a single reference, which described it as being poor by comparison with the analogous palladium-catalyzed version [6]. Nonetheless, Yamamoto and Tsuji independently described the first rhodium-catalyzed decarboxylation of allylic phenyl carbonates and the intramolecular decarboxylative aUylation of aUyl y9-keto carboxylates respectively [7, 8]. These findings undoubtedly laid the groundwork for Tsuji s seminal work on the regiospecific rho-... 

A-Alkylhydroxylamines react with substituted allyl acetates (e.g. 15, equation 11) in palladium catalyzed addition-elimination reactions giving the corresponding A-alkyl, A-allylhydroxylamines 16. The reaction proceeds with high regioselectivity but complete racemization. A similar reaction with 0-acyl hydroxamic acids has been carried out using allylic a-alkoxycarbonyloxyphosphonates. ... 

Another example of a dendritic effect observed for a core-funtionalized dendritic catalyst was described by Oosterom et al. (19) for allylic alkylation reactions (Section II). The palladium complexes of 5 catalyzed the alkylation of 3-phenylallyl acetate with sodium diethyl methylmalonate. It was observed that the reaction rate decreased and the fraction of branched product increased with increasing generation number. 

In sharp contrast to a fully developed asymmetric palladium-catalyzed allylic substitution as described in the previous sections of this chapter, similar reactions using transition metal complexes other than palladium have not yet been fully investigated and their application to organic synthesis is quite limited at the present. In this section, examples of Cu-, Ni-, Pt-, Rh-, Ir-, Ru-, Mo-, and W-catalyzed allylic alkylation are summarized including recent developments in this field. 

As described in many reviews, Trost and his co-workers have carried out a pioneering work on the molybdenum-and tungsten-catalyzed allylic alkylation of allylic esters regioselectivity of the reaction is often complementary to the palladium-catalyzed allylic alkylation. The first asymmetric version was disclosed by Pfaltz and Lloyd-Jones in 1995 (Equation (63)). They used a catalytic amount of a novel tungsten complex, prepared from [W(CO)3(MeCN)3] or [W(cycloheptatriene) (COIs] and optically active (diphenylphosphino)phenyloxazolines 57, for the allylic alkylation of 3-aryl-2-propenyl phosphate with dimethyl sodiomalonate to isolate the corresponding branched alkylated compounds as a major isomer with an excellent enantioselectivity (96% ee). Unexpectedly, 3-aryl-2-propenyl carbonates are shown to be unreactive. It is worth noting that an isostructural molybdenum complex does not promote the catalytic alkylation under the same reaction conditions. In contrast, Lloyd-Jones and Lehmann reported the stereocontrolled... 

Hallberg and his co-workers reported in 1999 the first microwave-promoted asymmetric palladium-catalyzed allylic alkylation of acyclic and cyclic allylic esters with dimethyl malonate, using some chiral ligands 57 and 118 (Equations (65) and (55))3 s,l6Sa,i6Sb both cases, microwave irradiation reduces reaction time without any loss of enantio-selectivity. The same group successfully applied this reaction system to the molybdenum-catalyzed allylic alkylation (Equation ((,7)) 60.160 -l60. 

The New Challenger—the Potential of Glycerol in Green Chemistry Enhancing the efficiency of a synthetic reaction. Palladium-catalyzed allylic alkylation... 

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