Palladium electrophilic

The effect of the nature of the electrophile on the stereoselectivity of reactions with substrates containing a terminal alkene and an allylic substituent is dramatically illustrated by some recent results with palladium electrophiles.124 Cyclizations of 3-methyl- or 3-phenyl-5-hydroxyalkenes with palladium catalysts proceed with high selectivity (>9 1) for the 2,3-trans isomer (equation 41).50-124 It is suggested that the steric interactions of the palladium-alkene complex affects the stereochemistry of these cyclizations. In some related cyclizations to form tetrahydropyran products (equation 42 and Table 10), reaction with iodine in the presence of sodium bicarbonate gives a different major diastereomer from cyclization with mercury(II) trifluoroacetate or palladium chloride.123... 

Pd(II) compounds coordinate to alkenes to form rr-complexes. Roughly, a decrease in the electron density of alkenes by coordination to electrophilic Pd(II) permits attack by various nucleophiles on the coordinated alkenes. In contrast, electrophilic attack is commonly observed with uncomplexed alkenes. The attack of nucleophiles with concomitant formation of a carbon-palladium r-bond 1 is called the palladation of alkenes. This reaction is similar to the mercuration reaction. However, unlike the mercuration products, which are stable and isolable, the product 1 of the palladation is usually unstable and undergoes rapid decomposition. The palladation reaction is followed by two reactions. The elimination of H—Pd—Cl from 1 to form vinyl compounds 2 is one reaction path, resulting in nucleophilic substitution of the olefinic proton. When the displacement of the Pd in 1 with another nucleophile takes place, the nucleophilic addition of alkenes occurs to give 3. Depending on the reactants and conditions, either nucleophilic substitution of alkenes or nucleophilic addition to alkenes takes place. 

Together with reactions named after Heck and Suzuki, the Stille reac-tion belongs to a class of modern, palladium-catalyzed carbon-carbon bond forming reactions. The palladium-catalyzed reaction of an organotin compound 2 with a carbon electrophile 1 is called Stille coupling. 

Oxidative addition—Reaction of the carbon electrophile with palladium-(0) complex 5 to give a palladium-(II) complex 6. 

The palladium component may be added to the reaction mixture as Pd(0)- as well as Pd(II)- compound in the latter case the Pd(II)- first has to be reduced to Pd(0)- by excess stannane. Since the first publication on this coupling method by Stille in 1978, this reaction has gained increased importance in synthetic organic chemistry. This is due to the fact that many different types of substrates can be used in this reaction. The following table lists possible carbon electrophiles and stannanes that can be coupled in any combination. 

The electrophilic character of the palladium atom in the complexes formed by oxidative addition of aryl halides and alkenyl halides to palladium(o) complexes can be exploited in useful ways. 

The late Professor J. K. Stille pioneered the development of a very effective and versatile palladium-mediated C-C bond forming method - the palladium-catalyzed cross-coupling of organic electrophiles with organostannanes.48 This process continues to enjoy much success in organic synthesis because it proceeds in high yields under mild reaction conditions and because it tolerates a... 

In the direct coupling reaction (Scheme 30), it is presumed that a coordinatively unsaturated 14-electron palladium(o) complex such as bis(triphenylphosphine)palladium(o) serves as the catalytically active species. An oxidative addition of the organic electrophile, RX, to the palladium catalyst generates a 16-electron palladium(n) complex A, which then participates in a transmetalation with the organotin reagent (see A—>B). After facile trans- cis isomerization (see B— C), a reductive elimination releases the primary organic product D and regenerates the catalytically active palladium ) complex. 

An approach to isobacteriochlorins1 ln-e makes use of Pd(II) or metal-free bilatrienes 1 as starting materials. Cyclization of the corresponding bilatriene derivatives is induced by base in the presence of palladium(II) or zinc(II) which exercise a template effect. Zinc can be readily removed from the cyclized macrotetracycles by acid whereas palladium forms very stable complexes which cannot be demetalated. Prior to the cyclization reaction, an enamine is formed by elimination of hydrogen cyanide from the 1-position. The nucleophilic enamine then attacks the electrophilic 19-position with loss of the leaving group present at the terminal pyrrole ring. 

The procedure in Section C is representative of the synthesis of non-natural a-amino acids featuring the palladium cross coupling reaction of a (1-alaninc organozinc derivative with aromatic electrophiles. This methodology has been successfully extended with modifications to both the electrophile and the catalyst as shown in the Table. 

Chianese AR, Lee SJ, Gagne MR (2007) Electrophilic activation of aUcenes by platinum(II) so much more than a slow version of palladium(II). Angew Chem Int Ed 46 4042-4059... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Palladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 NicolaouKC, KingNP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natural Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

The Suzuki-Miyaura reaction, first reported by Suzuki and co-workers in 1979 [87], is the metal-mediated (often palladium) coupling of organic electrophiles such as alkenyl... 

Hydroboration of alkenes or alkynes followed by cross-coupling with organic electrophiles provides a straightforward method for the carbon-carbon bond formation (Scheme 1-19). The hydroboration of thioalkynes with catecholborane in the presence of a nickel or palladium catalyst yields P-(aLkylthio)-l-alkenylboronates (72a)... 

They demonstrated that electron-deficient R groups and electron-rich R substituents at S accelerated the reductive elimination. They proposed 123 (Lj = DPPE, R = Ph, R = Ar) as a transition state, where R acts as an electrophile and thiolate as a nucleophile. The Hammet plot for the reductive elimination showed that the resonance effect of the substituent in R determines the inductive effect of the R group, and the effect in SR showed an acceptable linear relationship with the standard o-values. The relative rate for sulfide elimination as a function of the hybrid valence configuration of the carbon center bonded to palladium followed the trend sp > sp spl... 

The synthetic utility of the mercuration reaction derives from subsequent transformations of the arylmercury compounds. As indicated in Section 7.3.3, these compounds are only weakly nucleophilic, but the carbon-mercury bond is reactive to various electrophiles. They are particularly useful for synthesis of nitroso compounds. The nitroso group can be introduced by reaction with nitrosyl chloride73 or nitrosonium tetrafluoroborate74 as the electrophile. Arylmercury compounds are also useful in certain palladium-catalyzed reactions, as discussed in Section 8.2. 

Chapter 11 focuses on aromatic substitution, including electrophilic aromatic substitution, reactions of diazonium ions, and palladium-catalyzed nucleophilic aromatic substitution. Chapter 12 discusses oxidation reactions and is organized on the basis of functional group transformations. Oxidants are subdivided as transition metals, oxygen and peroxides, and other oxidants. 

Nickel(O) complexes are extremely effective for the dimerization and oligomerization of conjugated dienes [8,9]. Two molecules of 1,3-butadiene readily undergo oxidative cyclization with a Ni(0) metal to form bis-allylnickel species. Palladium(O) complexes also form bis-allylpalladium species of structural similarity (Scheme 2). The bis-allylpalladium complexes show amphiphilic reactivity and serve as an allyl cation equivalent in the presence of appropriate nucleophiles, and also serve as an allyl anion equivalent in the presence of appropriate electrophiles. Characteristically, the bis-allylnickel species is known to date only as a nucleophile toward carbonyl compounds (Eq. 1) [10,11],... 

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