Arylation of nucleophiles

The mechanism of the nickel (0) catalyzed arylation of nucleophiles corresponds to this catalytic cycle according mostly to the results of Kochi (ref. 70) (Fig. 4). 

The use of diaryliodonium salts for direct arylations of nucleophilic species is a well-established practice. Examples of C-heteroatom bond formation by this approach, including uncatalyzed arylations of dialkyl phosphite, thiocarboxy-late, arylthiosulfonate, dialkyl phosphorothiolate, arylselenolate, and aryltel-lurolate salts with symmetrical diaryliodonium halides, are shown in (Scheme 40) [110-115]. 

Although not widely used as a route to organic tellurium compounds, the arylation of nucleophilic tellurium species has been considered for this purpose. In Scheme 32, some illustrative examples of such methods are... 

The arylation of nucleophiles by reaction with diaryliodonium salts can be greatly facilitated by copper catalysis. This effect was observed by Beringer et al in the thermal decomposition of diaryliodonium halides as well as by Caserio et al in the hydrolysis of diaryliodonium salts. 2 jhe thermal decomposition of diphenyliodonium chloride shows a reduced activation energy upon copper catalysis Ea = 19 kcal/mole in Methylene glycol in the presence of CuCl instead of 31 kcal/mole in the absence of catalyst.From the synthetic point of view, the copper-catalysed arylation with diaryliodonium salts has been particularly useful in the case of a number of reactions involving heteroatomic nucleophiles, in particular for 5-, 5e-, O- and N-arylation reactions. 

The mechanism of the amines or alcohols arylation catalyzed by nickel(II) complexes has not been elucidated until now (refs. 7, 17), even though the arylation of nucleophiles catalyzed by nickel(0) complexes is better understood. In this last case it is generally admitted that the reaction proceeds by an oxidative addition step, followed by a nucleophilic substitution, and then a reductive elimination of the arylation product (Scheme 4). According to the work of Kochi (ref. 18), the oxidative addition of the haloarene on a nickel(O) complex takes place through a monoelectronic transfer from the metal to the aryl halide with simultaneous formation of a nickel(I) intermediate, the actual catalyst of the reaction (ref. 6). 

Accordingly the arylation of nucleophiles catalysed by the nickel(II) complex bipy2NiBr2 can be considered as a good synthetic tool and at least as an interesting alternative to the usual copper catalysis. 

Arylation. Traditionally, arylation of nucleophiles is carried out in the presence of copper catalysts, the use of FeCls as an alternative, with its scope has now been delineated. In the synthesis of diaryl ethers, l,3-di-t-butyl-l,3-propanedione serves an additive (ligand for the Fe ion) and CS2CO3 as base. A,A -Dimethylethylenediamine appears to be an excellent ligand in the reaction with A-nucleophiles (A-heterocycles, amides" ) in a nonpolar solvent (toluene) where a milder base (K3PO4) suffices, arylation of alkanethiols calls for t-BuONa. ... 

Diaryliodonium salts have found synthetic application as arylating reagents in reactions with various organic substrates under polar, catalytic, or photochemical conditions. Typical examples of arylations of nucleophiles under polar, non-catalytic conditions are shown in Scheme 3.271 and include the reactions of diaryliodonium salts with thiosulfonate anions 675 [861], fluoride anion [862,863], malonates 676 [864] and silyl enol ethers 677 [865]. 

It has been pointed out (p. 265) that nucleophilic attack upon a quaternary salt may have various consequences the nucleophile may replace substituents from the pyridine nucleus, it may attack and open the ring and it may displace the pyridine ring from the quaternizing group. Numerous examples of the first two kinds of reaction (pp. 200-51, 265), and of the third the important case of the formation of 4-substituted pyridines from 4-pyridyl-pyridinium chloride (pp. 210, 239,251) have been quoted. This last kind is a particular case of arylation of nucleophiles by arylpyridinium salts, and the general case of this reaction and analogous alkylations will now be considered. These are presumably Sjn2 reactions (but see p. 269). 

A number of mechanisms have been proposed for the arylation of nucleophiles by diaryliodine(III) reagents including radical coupling processes, nucleophilic aromatic substitution (SArAr) and ligand coupling on iodine(III). It is now thought... 

With the exception of the nuclear amination of 4-methylthiazole by sodium amide (341, 346) the main reactions of nucleophiles with thiazole and its simple alkyl or aryl derivatives involve the abstraction of a ring or substituent proton by a strongly basic nucleophile followed by the addition of an electrophile to the intermediate. Nucleophilic substitution of halogens is discussed in Chapter V. 

Kinetic studies of these reactions reveal that they follow a second order rate law Rate = [Aryl halide] [Nucleophile]... 

The reaction between an alkoxide ion and an aryl halide can be used to prepare alkyl aryl ethers only when the aryl halide is one that reacts rapidly by the addition-elim mation mechanism of nucleophilic aromatic substitution (Section 23 6)... 

The thermal, and more importantly, the photolytic decomposition of aryl azides in the presence of nucleophiles, generally amines or alcohols, is the commonest method for preparing 3H-azepines. In fact, jV-phenyl-3//-azepin-2-amine (32, R = Ph), the first example of a 3//-azepine, was prepared by thermal decomposition of phenyl azide in aniline.32... 

In a classic study in 1940, Crossley and coworkers demonstrated that the rates of nucleophilic substitution of the diazonio group of the arenediazonium ion in acidic aqueous solution were independent of the nucleophile concentration, and that these rates were identical with the rate of hydrolysis. Since that time it has therefore been accepted without question that these reactions proceed by a DN + AN mechanism, i.e., that they consist of a rate-determining irreversible dissociation of the diazonium ion into an aryl cation and nitrogen followed by rapid reactions of the cation with water or other nucleophiles present in solution (Scheme 8-6). 

ARYLATION OF HARD HETEROATOMIC NUCLEOPHILES USING BROMOARENES SUBSTRATES AND Cu, Ni, Pd-CATALYSTS... 

The arylation of different hard heteroatomic nucleophiles with arylbromides has been investigated using Pd, Ni or Cu-catalysts. 

The fundamental and pratical importance of arylation, particularly the arylation of heteroatomic nucleophiles, was several times emphasized in the last few years (refs. 1, 2) (eqn. 1). 

As shown in this table, the metal catalysts used in the literature are mostly complexes of Ni or Cu and less often Co or Pd. For soft nucleophiles, on the left of the table, the efficiency of the nickel catalysts was already reported. Here, are presented the investigations concerning the arylation of hard nucleophiles such as amines, alcohols or hydroxide anion, using Ni, Pd and Cu catalysts. 

Therefore, for the arylation of oxygenated nucleophiles, particularly of the alcohols, the investigations were focused on the nickel catalysts (Fig. 8). 

In connexion with the arylation of hard nucleophiles, it was interesting to reinvestigate the hydrolysis of arylhalides in presence of copper catalysts, which is in fact the arylation of hydroxide anion and represents an important industrial challenge (eqn. 2). 

---