Palladium-and Nickel-catalyzed Reactions

Nickel salts are also excellent catalysts, however, the nature of the ligands attached to the nickel metal center is very important and often needs to be carefully chosen to achieve high reaction yields. Interestingly, nickel on charcoal 

Functionalized heterocyclic zinc reagents are very useful building blocks for the preparation of polyfimctional heterocycles, as shown with the pyridylzinc derivative 430 prepared by reductive lithiation followed by a transmetallation with zinc 

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Formally copper catalyzed couplings are analogous to palladium and nickel catalyzed reactions. Carbon-carbon and carbon-heteroatom bonds can be formed in such transformations alike. From the mechanistic point of view there is a significant difference between nickel, palladium and copper catalyzed processes however. While in the former cases the catalyst usually oscillates between the 0 and +2 oxidation states, in copper mediated transformations the common oxidation numbers are +1, +2 and +3. 

E. Negishi, in Organozinc Reagents A Practical Approach, P. Knochel, and P. Jones, Eds., Oxford University Press, Oxford, 1999, 213-243. Palladium- and Nickel-Catalyzed Reactions of Organozinc Compounds. T. Hosokawa and S.-I. Murahashi, in Chemistry for the list Century Monographs Transition Metal Catalyzed Reactions, S.-I. Murahashi and S. G. Davies, Eds., Blackwell Science, Oxford, 1999, Palladium-Catalysed Oxidation of Alkenes. 

Before 1970, the reactions of aryl halides (ArX) with nucleophiles were restricted to electron-deficient aryl halides via S Ar mechanisms. The reactivity of aryl hahdes in S Ar reactions decreases in the order ArF>ArCl>ArBr ArI [1]. The range of reactive nucleophiles was narrow, and reactions of alkenes or alkynes were not known. The discovery in 1968 of oxidative additions of palladium(O) (Fitton [2a]) and then nickel(O) (Kochi [2b]) with aryl hahdes (ArI>ArBr>ArCl) that generate ArM XL (M=Pd, Ni) paved the way to new palladium- and nickel-catalyzed reactions of aryl hahdes with C-nucleophiles, leading to the formation of C—C bonds. Palladium- or nickel-catalyzed cross-couphng reactions are described herein, following the historical order of discovery. 

Other successful examples of catalysts containing NHC ligands are found in palladium- and nickel-catalyzed carbon-carbon bond formations. The catalyst development with these metals has focused in particular on Heck-type reactions, especially the Mizoroki-Heck reaction itself [Eq. (42)] and various cross coupling reactions [Eq. (43)], e.g., the Suzuki-Miyaura reaction ([M] = and the Kumada-Corriu reaction ([M] = MgBr). " Related reactions like the Sonogashira coupling [Eq. (44)]326-329 Buchwald-... 

Ishikawa and coworkers have studied the unique reactivity of strained cyclic disilanes (Equation 9.11) [35]. Transition metals, especially those of Group 10, readily insert into the Si—Si bond of disilacyclobutene 118 and can catalyze the addition of that bond across a variety of unsaturated acceptors. In the case of Ni(0)-catalyzed reactions of 118 with trimethylsilyl alkynes, insertion was found to occur both in a 1,2-and in a 1,1-fashion. The latter of these pathways implies a 1,2-silyl-migration, presumably occurring at the metal center. A nickel vinylidene intermediate was therefore proposed, though efforts to prove its existence were inconclusive. Similar vinylidene intermediates have been proposed by Ishikawa and coworkers to account for migrations observed in related palladium- and platinum-catalyzed reactions [36]. 

In spite of their relatively young age palladium and nickel catalyzed carbon-heteroatom bond forming reactions, also known as the Buchwald-Hartwig reaction, have gained significant importance amongst synthetic... 

Palladium- and nickel-catalyzed cross-coupling reactions... 

Recently, a number of studies have been aimed at expanding the scope of palladium- and nickel-catalyzed polycondensation reactions through new twists on established routes or the advent of entirely new reaction pathways. The Ni(0)-catalyzed homo-coupling polymerization of triflate-substituted benzenes 17, as shown in Scheme 22, was utilized to synthesize a number of PPP derivatives [74-76]. Structural characterization indicated that these polymers are para-linked,... 

Palladium-catalyzed reactions and cross-couplings are vital and widely used methods in the synthesis of organic compounds. Many examples have emerged utilizing pyran-2-ones and coumarins in palladium- and nickel-mediated reactions, and several of these are presented in this section. 

There is a substantial body of literature on the palladium- and nickel-catalyzed formation of aryl sulfides, selenides, and phosphines from aromatic and heteroaromatic halides. Progress on these reactions has continued with several recent contributions [47-50]. A review in 1997 covered the types of transformations that can be conducted and the types of catalysts used [51]. Particularly useful examples are the conversions ofbinaphthol to binaphthylphosphines... 

However, palladium and nickel catalyzed versions promise, at the moment, an even wider range of possibilities. The need to maintain the catalytic cycle by continuous regeneration of the zerovalent metal catalyst limits, nevertheless, the functionalizability of the metallated center in the cyclized intermediate. For the same reason, the readily accessible starting materials may contain various functional groups which are compatible with the reaction conditions and which may be of value for the syntheses of complex heterocycles such as alkaloids. Carbon monoxide insertion reactions of the cyclized a-metal intermediates were shown to afford monocyclic methyl carboxylates and/or annulated cyclopentanones (cyclopentenones) with concomitant stereocontrolled formation of up to four carbon-carbm bonds. 

Palladium- and Nickel-catalyzed C—C Bond Formation Reactions... 

Negishi, E., Takahashi, T., Baba, S., Van Horn, D. E., Okukado, N. Nickel- or palladium-catalyzed cross coupling. 31. Palladium- or nickel-catalyzed reactions of alkenylmetals with unsaturated organic halides as a selective route to arylated alkenes and conjugated dienes scope, limitations, and mechanism. J. Am. Chem. Soc. 1987,109, 2393-2401. 

PALLADIUM- AND NICKEL-CATALYZED CROSS-COUPLING REACTIONS... 

In a closely related palladium- or nickel-catalyzed reaction, diene halides, acetates or carbonates 12 can be cyclized via intramolecular metallo-ene reaction of the allylpalladium intermediates. Various subsequent reactions can follow, such as dehydropalladation59 64-122 or car-boxylation and further carbonylativc cyclization to bicyclic products60 65 67. Dicarborative addition reactions of the latter type and their synthetic use have been extensively reviewed 68-69. 

In recent decades much effort has been devoted to extending the scope of palladium, copper, and nickel-catalyzed reactions proceeding via aryl or vinyl metal intermediates [12]. These coupling reactions have enabled the formation of many kinds of carbon-carbon and carbon-heteroatom connections that were previously very difficult to realize. Metal-mediated transformations have proven especially valuable for introduction of substituents to aromatic core structures. They allow the presence of a wide variety of functional groups and perform equally well in both inter and intramolecular applications. Furthermore, in homogeneous catalysis,... 

Palladium- and nickel-catalyzed coupling reactions are recognized to be among the most powerful carbon-carbon bond-forming reactions available to the synthetic organic chemist (Equation 2.1) [1] ... 

The low reactivity of aryl chlorides is usually attributed to the strength of the C—Cl bond (bond dissociation energies for Ph-X Cl, %kcalmor Br, SlkcalmoT I, 65kcalmoT ), which leads to a reluctance by aryl chlorides to oxidatively add to either Pd(0) or Ni(0), which is a critical initial step in palladium- and nickel-catalyzed coupling reactions (Scheme 2.1) [6, 7]. 

The paUadium-catalyzed reactions occurred with the simple combination of [Pd(allyl) Cl]j and added phosphine, or with Pd(PPh3) and an acid co-catalyst. The scope of these reactions encompassed the additions of arylamines. As shown in Equation 16.81, reaction of various arylamines with cyclohexadiene occurred with high enantioselectivity using Trost s ligand. This ligand is discussed in more detail in Chapter 20. These reactions, and nickel-catalyzed reactions, occur by nucleophilic attack of amines on ir-allyl intermediates generated by protonation of diene complexes or insertion of dienes into palladium hydrides. 

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