Aryl halides Arylic oxidation

Perfluoroalkyl or -aryl halides undergo oxidative addition with metal vapors to form nonsolvated fluonnated organometallic halides and this topic has been die subject of a review [289] Pentafluorophenyl halides react with Rieke nickel, cobalt, and iron to give bispentafluorophenylmetal compounds, which can be isolated in good yields as liquid complexes [290] Rieke nickel can also be used to promote the reaction of pentafluorophenyl halides with acid halides [297] (equation 193)... 

In a Kumada-Corriu reaction, an aryl halide is oxidatively coupled with a homogeneous nickel(ll)-phosphine catalyst [2], This species reacts with a Grignard reagent to give biaryl or alkylaryl compounds. Later, palladium-phosphine complexes were also successfully applied. By this means, stereospecific transformations were achieved. 

The first step, as usual with aryl halides, is oxidative addition of Pd(0) to the C-I bond. This step makes C2 reactive. Coordination of the alkyne to Pd(IE) and insertion makes the C2-C7 bond and gives an alkenylpalladium(II) complex. Finally, coordination of N to Pd(IE), removal of HI by the base, and reductive elimination provides the product and regenerates Pd(0). 

Recent development of the Heck reaction has also led to greater understanding of its mechanistic details. The general outlines of the mechanism of the Heck reaction have been appreciated since the 1970s and are discussed in numerous reviews [2,3]. More recently, two distinct pathways, termed the neutral and cationic pathways, have been recognized [2c-g,3,7,8,9]. The neutral pathway is followed for unsaturated halide substrates and is outlined in Scheme 8G. 1 for the Heck cyclization of an aryl halide. Thus, oxidative addition of the aryl halide 1.2 to a (bisphosphine)Pd(O) (1.1) catalyst generates intermediate 1.3. Coordination of... 

A number of different polar and nonpolar covalent bonds are capable of undergoing the oxidative addition to M( ). The widely known substrates are C—X (X = halogen and pseudohalogen). Most frequently observed is the oxidative addition of organic halides of sp2 carbons, and the rate of addition decreases in the order C—I > C—Br >> C—Cl >>> C—F. Alkenyl halides, aryl halides, pseudohalides, acyl halides and sulfonyl halides undergo oxidative addition (eq. 2.1). 

Innovations in the chemistry of aromatic compounds have occurred by recent development of many novel reactions of aryl halides or pseudohalides catalysed or promoted by transition metal complexes. Pd-catalysed reactions are the most important [2,29], The first reaction step is generation of the arylpalladium halide by oxidative addition of halide to Pd(0). Formation of phenylpalladium complex 1 as an intermediate from various benzene derivatives is summarized in Scheme 3.1. 

Another example of transient formation of a palladacycle is the Pd-mediated ortho-alkylation and ipso-vinylation of aryl iodides depicted in Scheme 8.23. In this multicomponent reaction the ability of norbomene to undergo reversible arylation and palladacycle formation is exploited. This reaction also illustrates that aryl halides undergo oxidative addition to Pd faster than do alkyl halides, and that aryl-alkyl bond-formation by reductive elimination also proceeds faster than alkyl-alkyl bond-formation. The large excess of alkyl iodide used in these reactions prevents the formation of biaryls. Benzocyclobutenes can also be formed in this reaction, in particular when the alkyl group on the aryl iodide is sterically demanding or when a secondary alkyl iodide is used [161]. 

Early preparations of active zinc utilized the potassium or sodium metal reduction of anhydrous zinc salts in refluxing THF or DME (Protocol l).3,8 These highly divided zinc powders displayed high reactivity towards organic halides in oxidative addition. Alkyl iodides and bromides reacted with the zinc powders at room temperature. Even aryl bromides and iodides would react to form the corresponding arylzinc iodides or bromides at refluxing... 

The mechanism of the oxidative addition of aryl bromides to the bis-P(o-tolyl)3 Pd(0) complex 3 was surprising [196]. It has been well established that aryl halides undergo oxidative addition to L2Pd fragments [197 -200] thus, one would expect oxidative addition of the aryl halide to occur directly to 3 and ligand dissociation and dimerization to occur subsequently. Instead, the addition of aryl halide to [Pd[P(o-tolyl)3]2] occurs after phosphine dissociation, as shown by an inverse first-order dependence of the reaction rate on phosphine concentration and the absence of any tris-phosphine complex in solution [196]. 

Closely related are the -acyl complexes of iron (115). These have been prepared by three methods. Loss of N2 from (112) in the presence of an alkyl halide gives oxidative addition see Oxidative Addition) to yield ) -acyl complexes for some phosphine ligands. Sodium amalgam reduction of Fe halide complexes (116), and exposme of the resulting (117) to an alkyl halide, gives similar complexes (equation 24). Finally, placement of iron alkyl (aryl) complexes (118) under a CO atmosphere results in insertion to afford complexes (119) (equation 25). ... 

The reactivity order of aryl halides in oxidative additions is as follows ... 

Acyclic and cyclic ethers are synthesized by the reaction of activated alcohols with alkoxide or aryl oxide anions. Alkyl halides and epoxides can also be utilized as versatile electrophiles for the preparation... 

Zhu, L., Wehmeyer, R. M., Rieke, R. D. The direct formation of functionalized alkyl(aryl)zinc halides by oxidative addition of highly reactive zinc with organic halides and their reactions with acid chlorides, -unsaturated ketones, and allylic, aryl, and vinyl halides. J. Org. Chem. 1991,56, 1445-1453. 

Under normal codeposition conditions, alkyl and aryl halides do not react with Sn or Pb atoms. However, Sn and Pb slurries can be prepared by codeposition of the metal vapors with solvents such as toluene, THF, or diglyme . Refluxing these slurries with organic halides yields oxidative addition products , e.g., an (Sn) -THF slurry with CH3I yields a mixture of CH3Snl3, (CH3)2Snl2, and (CH3)3SnI. The relative composition of... 

Alkenyl, allyl, and aryl halides undergo oxidative addition to Pd° complexes to form alkenyl-, allyl-, and aryl-palladium a-complexes which then react with carbon monoxide, alkenes and alkynes. 

The order of reactivities observed in S Ar displacement reactions often parallels the order of reactivity of aryl halides in oxidative additions to Pd(0). Likewise, the ease with which the oxidative addition occurs for heteroaryl halides can often be predicted on the basis of S Ar reactivity of a given substrate. In addition, a- and y-chloroheteroarenes are sufficiently activated for use in Pd-catalyzed reactions with a variety of different catalysts, whereas Pd-catalyzed reactions of unactivated aryl chlorides (e.g. chlorobenzene) typically require large, electron-rich phosphine or 7V-heterocychc carbene ligands [4]. 

Although In(I) halides do not insert directly into aryl-halide bonds, oxidative arylation does occur with In(I) halides and aryimercuriais in good yields The aryl-mercurial may be an arylmercurial halide or the bis(aryl)mercurial ... 

Aryl sulphonyl chlorides may also be synthesized from the sulphinyl chloride, by oxidation with chlorine, in 80% yield573 (equation 146) or dimethyl sulphoxide574. Sulphinate esters may also be utilized as the precursor to sulphonyl halide via oxidative halogenation. For example, methyl methanesulphinate is converted to methanesulphonyl chloride in excellent yield at 0°C568. 

A very large series of nitrosyl complexes, [Mo (NO)Tp XY] has been described where X and Y are halide, alkoxide, aryl oxide, alkyl or arylamide, alkyl or aryl thiolate groups. These diamagnetic (Mo(NO) + species are regarded as containing 16 valence electrons, with a formal metal oxidation state of II, assuming NO+ binding, and the metal center could... 

The reaction of metal halides with an alkoxide or aryl oxide (most commonly an alkali metal alkoxide), can result in metathetic exchange to give the required complex (equation 6). Such reactions can also result in the formation of heterometallic species (such as NaZr2(OR)4) this can be a problem when homometallic alkoxides are desired, but it is an important route to heterometallic alkoxides and aryloxides. The nature of the product can be influenced by the alkali metal, the alkoxide ligand, and the relative amounts of the... 

Palladium(O) exhibits a degree of nucleophilic character, thus electron-with-drawing substituents increase the reactivity of aryl halides in oxidative additions. This is exemplified in the heterocyclic context the inductive effect of C=N units allows 2-chloropyrimidine (it is slightly less reactive than bromobenzene), and even 3-chloropyridine to react (even the moderate inductive effect at the P-position gives rise to a significantly higher rate of reaction relative to chlorobenzene) although a more reactive catalyst is required for the latter case (cf. section 2.7.2.2). 

Mechanistic studies from Semmelhack s group showed that in the first step aryl halide undergoes oxidative addition to the low valent metal complex with formation of organometallic intermediate in a higher oxidation state [1,2]. For example, bis(l,5-cyclooctadienyl)nickel(0), Ni(COD)2, reacts with aryl halide (I) to give arylnickel(II) halide (VIII), which further reacts with another aryl halide molecule to form diarylnickel(IV) halide (IX). Each oxidative addition step includes substitution of ligands at metallic centre. 1,5-Cyclooctadiene (COD) dissociates from the nickel to form a coordinatively unsaturated metallic-centre, which does react with aryl halide. Biaryl II is formed by reductive elimination step from IX with liberation of nickel(II) halide [1,2], Scheme 1. 

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