Palladium catalysis addition-elimination reactions

Direct nucleophilic displacement of halide and sulfonate groups from aromatic rings is difficult, although the reaction can be useful in specific cases. These reactions can occur by either addition-elimination (Section 11.2.2) or elimination-addition (Section 11.2.3). Recently, there has been rapid development of metal ion catalysis, and old methods involving copper salts have been greatly improved. Palladium catalysts for nucleophilic substitutions have been developed and have led to better procedures. These reactions are discussed in Section 11.3. 

Another potentially powerfnl sequence arises by combining one or two intramolecular Heck-type couplings with an intra- or intermolecular Diels-Alder addition (for early examples of inter-intermolecular one-pot domino Heck-Diels-Alder reactions see Refs. [49] and [50]). An all-intramolecular version of such a sequence has been shown to proceed reasonably smoothly for terminally alkoxycarbonyl-substituted 2-bromotrideca-l,ll-dien-6-ynes under palladium catalysis at 130 °C. At 80 °C, the sequential reaction stops after the two consecutive Heck-type cyclizations and subsequent /3-hydride elimination to give a 1,3,6-triene apparently only the ( )-isomer undergoes the intramolecular Diels-Alder reaction, as the (Z)-l,3,6-triene is observed accompanying the tetracyclic system obtained at 130 °C (Scheme 36). 

Several studies have used palladium catalysis in the arylation of benzoxazoles. A palladium catalyst with a phosphine ligand allows their reaction with aryl mesylates without the requirement for acid or copper additives. In the reaction with arene-sulfonyl chloride, palladium is used in combination with copper. A plausible mechanism involves initial cupration of the benzoxazole followed by copper—palladium exchange and oxidative addition of the sulfonyl chloride to palladium to give (84). This intermediate may lose sulfur dioxide to give an aryl palladium species, which, on reductive elimination, yields 2-arylbenzoxazole. The arylation of benzoxazoles and benzthiazoles with aryl boronic acids is also catalysed by a combination of palladium... 

Palladium catalysis has become an important tool in synthesis due in large part to its ability to mediate a number of different fundamental transformations with low reaction barriers. These include oxidative addition and reductive elimination reactions, insertion and de-insertion (often (3-hydride elimination), nucleophilic ligand attack, or cycloaddition (Scheme 6.1). 

The possibilities for the formation of carbon-carbon bonds involving arenes have been dramatically increased in recent years by the use of transition metal catalysis. Copper-mediated reactions to couple aryl halides in Ulknann-type reactions [12, 13] have been known for many years, and copper still remains an important catalyst [14, 15]. However, the use of metals such as palladium [16,17] to effect substitution has led to such an explosion of research that in 2011 transition metal-catalyzed processes comprised more than half of the reactions classified as aromatic substitutions in Organic Reaction Mechanisms [18]. The reactions often involve a sequence outlined in Scheme 6.6 where Ln represents ligand(s) for the palladium. Oxidative addition of the aryl halide to the paiiadium catalyst is followed by transmetalation with an aryl or alkyl derivative and by reductive elimination to give the coupled product and legeuCTate the catalyst. Part 6 of this book elaborates these and related processes. 

As mentioned at the very start of the chapter, +2 is the most common oxidation state for Group 10 metals due to the d electron configuration. For palladium, Pd(II) species have played a pivotal role in elementary reactions in palladium-catalysis, for example, oxidative addition/reductive elimination, and thus have received extensive research interest historically. In the following section, the advancements of dipalladium(II) compounds with Pd(II) - Pd(II) bonds in the last decade will be summarized. 

These reactions complement recently developed palladium(0)amination reactions [146,147,148] and related procedures using a copper(I) [149] - or ni-ckel(O) [151] - catalysis. As indicated above, the mild reaction conditions are compatible with a range of functional groups. Functionalized arylmagnesium chlorides such as 309 prepared by an I/Mg-exchange readily undergo addition reactions to aryl oxazolines. The addition-elimination of 309 to the -methoxy aryloxa-zoline followed by an ortHo-lithiation and substitution with ethylene oxide leads to a polyfunctionalized aromatic intermediate 310 for alkaloid synthesis (Scheme 4.68) [165]. 

Amine activatitMi pathway has been well studied in catalysis by lanthanides, early transition metals, and alkali metals. In metal amide chemistry of late transition metals, there are mainly two pathways to synthesize metal amide complexes applicable under hydroamination conditions [54], One is oxidative addition of amines to produce a metal amide species bearing hydride (Scheme 8a). The other gives a metal amide species by deprotonation of an amine metal intermediate derived from the coordination of amines to metal center, and it often occurs as ammonium salt elimination by the second amine molecule (Scheme 8b). Although the latter type of amido metal species is rather limited in hydroamination by late transition metals, it is often proposed in the mechanism of palladium-catalyzed oxidative amination reaction, which terminates the catalytic cycle by p-hydride elimination [26]. Hydroamination through aminometallation with metal amide species demands at least two coordination sites on metal, one for amine coordination and another for C-C multiple bond coordination. Accordingly, there is a marked difference between the hydroamination via C-C multiple bond activation, which demands one coordination site on metal, and via amine activation. 

Terminal alkynes react with propargylic carbonates at room temperature to afford the alka-l, 2-dien-4-yne 14 (allenylalkyne) in good yield with catalysis by Pd(0) and Cul[5], The reaction can be explained by the transmetallation of the (7-allenylpailadium methoxide 4 with copper acetylides to form the allenyKalk-ynyl)palladium 13, which undergoes reductive elimination to form the allenyl alkyne 14. In addition to propargylic carbonates, propargylic chlorides and acetates (in the presence of ZnCb) also react with terminal alkynes to afford allenylalkynes[6], Allenylalkynes are prepared by the reaction of the alkynyl-oxiranes 15 with zinc acetylides[7]. 

HCHO and PH3 proceeds in the presence of K2PtCl4 at room temperature and affords the crystalline product in an essentially quantitative yield in 2.5 h [4]. Palladium compounds are also active in the catalysis [5]. In these reactions the active species is believed to be zero valent. Two mechanistic possibilities have been proposed as illustrated in Scheme 2. The first elemental process involved in the catalytic cycle is oxidative addition of a P-H bond, which is well precedented [6]. In one of the mechanistic possibilities the processes that follow the oxidative addition are the insertion of the C=0 bond into H-M species and P-C reductive elimination, the latter of which is also precedented [7]. In the other, the coordinating phosphide ligand makes a nucleophilic attack [8] at the formaldehyde carbon forming zwitterionic species. 

The synthesis of unsymmetrical biaryls 8 from two monoaryl species involves the coupling of a metallated aromatic molecule 6 with an aryl halide or triflate 4 under the action of palladium(O) catalysis. The reaction involves a catalytic cycle in which palladium(O) inserts into the C-halogen bond via an oxidative addition to generate an arylpalladium(II) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(II) complex 7. The biaryl product is formed by reductive elimination. In the process, Pd(0) is regenerated and this can then react with a second molecule of aryl halide. Pd(0) is therefore a catalyst for the reaction. 

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