Electrophilic Palladium Complexes

Organic Synthesis Using Transition Metals, Second Edition. Roderick Bates. 2012 John Wiley Sons, Ltd. Published 2012 by John Wiley Sons, Ltd. 

Operates appears to depend on the concentration of the different ligands available to palladium the latter is likely to operate under the conditions employed in the industrial process. P-Hydride elimination then gives an if-enol complex 6.4. Reinsertion generates an isomeric -complex 6.5, which undergoes a second p-hydride elimination to give acetaldehyde. The reductive elimination of HCl has, at this point, reduced the palladium to zero, so the process is not catalytic. Copper salts are included copper(II) oxidizes Pd(0) to Pd(II), but is reduced to copper(I). The reaction is mn in the presence of air. Oxygen from air re-oxidizes the copper(I) to copper(II) in the second catalytic cycle. 

The chemistry of the Wacker reaction is not limited to ethylene, but may be extended to a wide range of alkenes, and is useful throughout organic synthesis. For the synthesis of complex molecules, the Wacker 

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Fujiwara s research group have developed an array of catalytic arene functionalizations employing electrophilic palladium complexes (Equation (65)).66... 

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. 

Addition of diphenyl disulfide (PhS)2 to terminal alkynes is catalyzed by palladium complexes to give l,2-bis(phe-nylthio)alkenes (Table 3)168-172 The reaction is stereoselective, affording the (Z)-adducts as the major isomer. A rhodium(i) catalyst system works well for less reactive aliphatic disulfides.173 Bis(triisopropylsilyl) disulfide adds to alkynes to give (Z)-l,2-bis(silylsulfanyl)alkenes, which allows further transformations of the silyl group to occur with various electrophiles.174,175 Diphenyl diselenide also undergoes the 1,2-addition to terminal alkynes in the presence of palladium catalysts.176... 

Thiazole is a jt-electron-excessive heterocycle. The electronegativity of the N-atom at the 3-position makes C(2) partially electropositive and therefore susceptible to nucleophilic attack. In contrast, electrophilic substitution of thiazoles preferentially takes place at the electron-rich C(5) position. More relevant to palladium chemistry, 2-halothiazoles and 2-halobenzothiazoles are prone to undergo oxidative addition to Pd(0) and the resulting o-heteroaryl palladium complexes participate in various coupling reactions. Even 2-chlorothiazole and 2-chlorobenzothiazole are viable substrates for Pd-catalyzed reactions. 

Palladium complexes have been used for the electroreductive cycliza-tion of Ai-alkenyl-2-bromoanilines to the corresponding indoline derivatives (Scheme 69) [101]. The postulated carban-ion intermediate undergoes a reaction with the electrophiles (H+, CO2). 

Bidentate ferrocene ligands containing a chiral oxazoline substituent possess both planar chiral and center chiral elements and have attracted much interest as asymmetric catalysts.However, until recently, preparation of such compounds had been limited to resolution. In 1995, four groups simultaneously communicated their results on the asymmetric synthesis of these structures using an oxazoline-directed diastereoselective lithiation (Scheme 8.141). " When a chiral oxazolinylferrocene 439 was metalated with butyllithium and the resulting aryllithium species trapped with an electrophile, diastereomer 442 was favored over 443. The structure of the major diastereomer 442 was confirmed, either by conversion to a compound of known stereochemistry or by X-ray crystallography of the product itself or of the corresponding palladium complex. ... 

Arylzinc species prepared via the sacrificial anode process and from aryl halides in the presence of a nickel 2,2 -bipyridine, as already reported in Section . .1, were found totally unreactive towards common electrophiles such as aldehydes, carboxylic anhydrides or activated alkyl halides. However, they react with some electrophiles when they are activated by the presence of a catalytic amount of copper salts (10 mol% Cul) together with tetramethylethylene diamine (1MEDA) as described by Knochel and Singer on the ArZnX—CuCN metal exchange47 or when the reaction is catalyzed by palladium complex. 

Another variant of the Heck reaction which is important in heterocyclic chemistry utilizes five membered heterocycles as olefin equivalent (2.2.)7 It is not clear whether the process, coined as heteroaryl Heck reaction follows the Heck mechanism (i. e. carbopalladation of the aromatic ring followed by //-elimination) or goes via a different route (e.g. electrophilic substitution by the palladium complex or oxidative addition into the C-H bond). Irrespective of these mechanistic uncertainties the reaction is of great synthetic value and is frequently used in the preparation of complex policyclic structures. 

Allyl esters, carbonates, and carbamates readily undergo C-O bond cleavage upon reaction with palladium(O) to yield allyl palladium(II) complexes. These complexes are electrophilic and can react with nucleophiles to form products of allylic nucleophilic substitution. Linkers based on this reaction have been designed, which are cleavable by treatment with catalytic amounts of palladium complexes [165,166], For the immobilization of carboxylic acids, support-bound allyl alcohols have proven suitable (Figure 3.12, Table 3.7). 

Anilines with strongly electron-withdrawing groups or diarylamines [38] are only weak nucleophiles, and might require deprotonation to react with electrophiles at acceptable rates (Scheme 6.8). These anilines can also be allylated by allyl palladium complexes [34], Electron-deficient anilines are electrophiles themselves, and can transfer the aryl group to other nucleophiles by aromatic nucleophilic substitution [39]. 

The presence of chelating groups in those complexes is necessary to stabilize the intermediate aryl-palladium complex for isolation but it does not seem necessary to cause palladation. The chelating group does, however, tremendously accelerate the palladation. Aromatic compounds reactive to electrophilic substitution apparently undergo palladation with palladium acetate in acetic acid solution fairly readily at 100 °C or above. Of course, the arylpalladium acetates presumably formed, are not stable under these conditions, and they decompose very rapidly into biaryls and palladium metal 34,35,36) ag do aryl palladium salts prepared by the exchange route 24>. If the direct palladation is carried out in the presence of suitable olefins, arylation can be achieved, so far, however, only in poor yields, arid with concurrent loss of stereospecificity and formation of isomers and other side products 37.38). 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

It is very well known that jr-allyl palladium complex 1, which is a key intermediate for the Tsuji-Trost type allylation, has an electrophilic character and reacts with nucleophiles to afford the corresponding allylation products. We discovered that bis 7r-allyl palladium complex 2 is nucleophilic and reacts with electophiles such as aldehydes [27] and imines [28-32] (Scheme 2, Structure 2). We have also shown that bis 7r-allyl palladium complex 2 can act as an amphiphilic catalytic allylating agent it reacts with both nucleophilic and electrophilic carbons at once to produce double allylation products [33]. These complexes incorporate two allyl moieties that can bind with different hapticity to palladium (Scheme 3). The different complexes may interconvert by ligand coordination. The complexes 2a, 2b and 2c are called as r]3,r]3-bisallypalladium complex (also called bis-jr-allylpalladium complex), r)l,r)3-bis(allyl)palladium complex, -bis(allyl)palladium complex, respectively. Bis zr-allyl palladium complex 2 can easily be generated by reaction of mono-allylpalladium complex 1 and allylmetal species 3 (Scheme 4) [33-36]. Because of the unique catalytic activities of the bis zr-allyl palladium complex 2, a number of interesting cascade reactions appeared in the literature. The subject of the present chapter is to review some recent synthetic and mechanistic aspects of the interesting palladium catalyzed cascade reactions which in-... 

Related displacements with acetylenes9 and electrophilic olefins6 have been reported to give complexes formulated as [Pd [ P (C 6H 6) 3 2 (olefin or acetylene) ]. Also, oxidative additions of alkyl and aryl halides have been shown to occur giving palladium ) complexes, [Pd[P(C6H5)3 2(R)Cl].10... 

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