Palladium catalysis aryl halide reactions

This reaction is similar to 13-1 and, like that one, generally requires activated substrates. With unactivated substrates, side reactions predominate, though aryl methyl ethers have been prepared from unactivated chlorides by treatment with MeO in HMPA. This reaction gives better yields than 13-1 and is used more often. A good solvent is liquid ammonia. The compound NaOMe reacted with o- and p-fluoronitrobenzenes 10 times faster in NH3 at — 70°C than in MeOH. Phase-transfer catalysis has also been used. The reaction of 4-iodotoluene and 3,4-dimethylphenol, in the presence of a copper catalyst and cesium carbonate, gave the diaryl ether (Ar—O—Ar ). Alcohols were coupled with aryl halides in the presence of palladium catalysts to give the Ar—O—R ether. Nickel catalysts have also been used. ... 

Under all the conditions studied, addition of bare Si02-SH to Heck or Suzuki coupling reactions using a variety of bases, aryl halides and solvents resulted in complete cessation of the catalytic activity (35). These results suggest that catalysis with this precatalyst is also associated with labile palladium species that... 

Several reports have been made of a successful catalyzed addition/ substitution reaction resulting in direct attachment of phosphorus to aromatic rings. The preparation of mixed triarylphosphines has been accomplished by the reaction of tin- or silicon-substituted diphe-nylphosphines with aryl halides catalyzed by palladium reagents.74 A similar transformation has also been reported using nickel catalysis.75 The addition/substitution of diphenylphosphine to triflate functionalized phenolic linkages has been of use for the preparation of substances as analogues of tyrosine-related amino acid derivatives, accomplished with catalysis by palladium acetate (Equation 4.29).76... 

Recently, this reaction has been extensively studied since it is currently the only method to couple aryl Grignard reagents with secondary alkyl halides Indeed, secondary aUtyl halides do not react under palladium or nickel catalysis . On the other hand, let us recall that the coupling of secondary alkyl Grignard reagents with aryl halides leads to poor results (see above). 

It is reported that the palladium-catalysed intramolecular aromatization of 1,1 -dichloro-9/T-fluoren-9-yIidene (15) may lead to the formation of fullerene fragments.89 The amiulation reaction, under palladium catalysis, between iodoanflines and ketones may yield indole derivatives.90 There have also been studies of the palladium-catalysed carbonylation of o-iodophenols with allenes which may lead to l-benzopyran-4-one derivatives,91 of the intramolecular coupling of phenols with aryl halides,92 and of the intramolecular Heck aiylation of cyclic enamides.93... 

A new type of triaryl phosphine-functionalized imidazolium salt containing cations such as (6) has been prepared. Palladium complexes of (6) generated in situ have been used successfully in Heck-type reactions of aryl halides with acrylates and of 4-bromotoluene with styrene derivatives.34 The first Heck-type reaction of aryl halides with allenes has been reported. 1,3-Double arylations were observed with 3-substituted-l,2-allenyl sulfones, while 1-monoarylation was favoured with 3,3-disubstituted-l,2-allenyl sulfones.35 It has been shown that the a-arylation of methane-sulfonamides (7) may be achieved using palladium catalysis reaction proceeds through the sulfonamide enolates.36 It is also reported that palladium cross-coupling of alkynes with /V - (3 - i odophe n y I an i I i ncs) may lead to the formation of substituted carbazoles.37... 

In the last few years numerous reports have been published in the field of microwave-promoted aryl halide cyanation, utilizing nickel [71], palladium [72,73] and copper [74,75] catalysis. Even water [75] and ionic liquids [76] have proven useful as solvents in these processes. Srivastava and Collibee have exemplified a swift and dynamic procedure using polymer-supported triphenyl phosphine to enable easy subsequent removal through filtration [72]. As shown in Scheme 19, both bromides and iodides could be activated using palladium catalysis in DMF. Even without optimization of the individual reaction times, the overall process time involving simple filtration and extraction for compound isolation appears to be short. 

As described in Section III.1.4.1.1, the catalytic direct arylation reactions of aromatic compounds occurs effectively via C-H bond cleavage when the substrates are appropriately functionalized. On the other hand, various five-membered heteroaromatic compounds involving one or two heteroatoms, even without a functional group, are known to undergo arylation, usually at their 2- and/or 5-posi-tion(s), on treatment with aryl halides under the action of palladium catalysis. The coupling has recently been developed significantly [1, 2]. Representative examples with some mechanistic discussion are summarized in this section. 

The coupling of terminal alkynes with aryl or vinyl halides under palladium catalysis is known as the Sonogashira reaction. This catalytic process requires the use of a palladium(0) complex, is performed in the presence of base, and generally uses copper iodide as a co-catalyst. One partner, the aryl or vinyl halide, is the same as in the Stille and Suzuki couplings but the other has hydrogen instead of tin or boron as the metal to be exchanged for palladium. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

The palladium-catalyzed reaction of aryl halides with cyanides to give cyanobenzenes takes place under relatively mild conditions compared to the conventional method using a stoichiometric amount of CuCN [74]. Thus, palladium catalysis has been often employed. Recently, a number of effective methods for the cyanation have been reported. The reaction of aryl iodides with NaCN under two-phase conditions [75] and those of aryl triflates [76, 77] and aryl chlorides [78] with Zn(CN)2 occur with good efficiency, while these are considered to proceed via mechanism B. 

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. 

There are a number of commonly used reactions of this type and many are named after the chemists who discovered them. They differ, among other things, in the exact nature of the metallic component. One of the first to be developed extensively was the Stille coupling, which specifically involves the coupling of an arylstannane with an aryl halide or triflate under the action of palladium catalysis (Scheme 10.19). 

---