Palladium-catalyzed allylic alkylation

Additions of carbon nucleophiles to vinylepoxides are well documented and can be accomplished by several different techniques. Palladium-catalyzed allylic alkylation of these substrates with soft carbon nucleophiles (pKa 10-20) proceeds under neutral conditions and with excellent regioselectivities [103, 104]. The sul-fone 51, for example, was cyclized through the use of catalytic amounts of Pd(PPh3)4 and bis(diphenylphosphino)ethane (dppe) under high-dilution conditions to give macrocycle 52, an intermediate in a total synthesis of the antitumor agent roseophilin, in excellent yield (Scheme 9.26) [115, 116]. 

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... 

Wong and co-workers have prepared various quaternary cx-nitro-cx-methyl carboxylic acid esters by the palladium-catalyzed allylic alkylation of a-nitropropionate ester (Eq. 5.59). The products can be kinetically resolved by using cx-chymotrypsin and are converted into optical active a-methyl cx-amino acids. Such amino acids are important due to the unique biological activity of these nonproteinogenic a-amino acids.82... 

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... 

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,... 

Equation 11.37 Asymmetric palladium-catalyzed allylic alkylation (BSA = N,0-bis(trimethylsilyl)acetamide). 

D. A. Evans, K R. Campos, J. S. Tedrow, F. E. Michael, M R. Gagne, Chiral Mixed Phosphorus/Surfur Ligands for Palladium-Catalyzed Allylic Alkylations and Amina-tions, J. Org Chem 1999, 64,2994-2995. 

Used in Asymmetric Palladium-Catalyzed Allylic Alkylations 320... 

Structural Identification of a Palladium Complex with a Chiral Sulfoxide Ligand Used in Asymmetric Palladium-Catalyzed Allylic Alkylations... 

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. 

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. 

Asymmetric Palladium-catalyzed Allylic Alkylation of Allylic Alcohols... 

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. 

Togni and his co-workers prepared dendrimers containing chiral ferrocenyldiphosphines and investigated the palladium-catalyzed allylic alkylation using these phosphines as chiral ligands to obtain the corresponding allylic alkylated compounds with a high enantioselectivity (up to 91% On the other hand, Malmstrom and his... 

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

As an extension of these studies on the use of sulfoximines in asymmetric reductions, BlNOL-derived phosphino sulfoximines of the 105 type were tested in both rhodium-catalyzed hydrogenations (yielding optically active diesters 104 or amino acid derivatives Scheme 2.1.1.35) and palladium-catalyzed allylic alkylations (not shown) in collaboration with Reetz and Gais [81, 82]. Here, enantioselectivities of up to >99 and 66% ee, respectively, were achieved. 

Palladium-Catalyzed Allylic Alkylation of Sulfur and Oxygen Nucleophiles -Asymmetric Synthesis, Kinetic Resolution and Dynamic Kinetic Resolution... 

Deerenberg, S., Schrekker, H.S., van Strijdonck, G.P.F., Kamer, P.C.J., van Leeuwen, P.W.N.M., Fraanje, J, and Goubitz, K. (2000) New chiral phosphine-phosphite hgands in the enantioselective palladium-catalyzed allylic alkylation. 

Range of Nucleophiles Employed in Palladium-catalyzed Allylic Alkylation 590... 

H. H. Baer and Z. S. Hanna, The preparation of amino sugars and branched-chain sugars by palladium-catalyzed allylic substitution of alkyl hex-2-enopyranosides, Can. J. Chem., 59 (1981) 889-906. 

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