Diazonium salts, Heck reactions

As noted in the paragraph dealing with diazonium salts in the Heck reaction, diazonium salts are versatile starting materials for cross-coupling reactions. Recently, Schmidt and co-workers used the Suzuki coupling in the presence of diazonium salts (Experimental Procedure below). 

Aiyl diazonium salts can be used coupled with alkenes in a Heck-like reaction (14-20). Other reactive aryl species also couple with aryldiazonium salts in the... 

Diazonium salts react with various nucleophiles in water (Eq. 11.62).106 In acidic aqueous solution, p-pheny I e ncbis di azo ni um ion reacts with alcohols more rapidly than it does with water.107 In the presence of nucelophiles such as halides, the substitution products are obtained. Furthermore, diazonium salts of aromatic compounds are excellent substrates for palladium-catalyzed coupling reactions such as the Heck-type reactions in water. 

Diazonium salts are another useful source of free radicals, and the formation of the reactive species can be achieved by reductive electrolysis or direct treatment with diazonium tetrafluoroborate salts [39]. By this route, several aryl derivatives could be introduced onto the nanotube sidewalls [40]. Aryl groups bearing halogen or alkyne functionalities are particularly interesting as they can be further reacted in Pd-catalyzed coupling reactions (Suzuki, Heck) or in click chemistry reactions to create products with great potential in materials science [41]. 

Heck reactions of arenediazonium salts can be conveniently carried out with [Pd(OAc)2] in ethanol. This method was extended to the one-pot sequential diazotation and allylation of aniUnes (Scheme 6.7). The latter were converted to the corresponding diazonium salts at 0 °C with NaNOa + 42 % HBF4. Ethyl acrylate and [Pd(OAc)2] were added and the reaction mixture was heated on a water bath for 1 h. The corresponding cinnamate esters were obtained in 65-80 % yield [22],... 

Arenediazonium salts reacted with tetramethyltin under very mild conditions in acetonitrile yielding the corresponding toluenes [63] and this reaction could be carried out in aqueous media, as well [64] (Scheme 6.29). Similar to the Heck reactions discussed in 6.1.1, a one-pot procedure could be devised starting from anilines, with no need for the isolation of the intermediate diazonium salts. The pH of the solutions should always be kept below 7 in order to avoid side reactions of the diazonium salts, however, unlike with the Heck reactions, HCl or H2SO4 can also be used. Since organotin compounds are easily hydrolysed in acidic solutions, a careful choice of the actual pH is required to ensure fast and clean reactions. Diaryliodonium salts are hydrolytically stable and also react smoothly with various organotin compounds (Scheme 6.29) [65]. 

Triazenes have been prepared by the treatment of resin-bound aromatic diazonium salts with secondary amines (Figure 3.27). Regeneration of the amine can be effected by mild acidolysis (Entry 1, Table 3.23). Triazenes have been shown to be stable towards bases such as TBAF, potassium hydroxide, or potassium tert-butoxide [454], and under the conditions of the Heck reaction [455]. Primary amines cannot be linked to supports as triazenes because treatment of triazenes such as R-HN-N=N-Ar-Pol with acid leads to the release of aliphatic diazonium salts into solution [373]. Triazenes derived from primary amines can, however, be used for the preparation of amides and ureas (see Section 3.3.4),... 

Support-bound triazenes, which can be prepared from resin-bound secondary aliphatic amines and aromatic diazonium salts [455], undergo cleavage upon treatment with acids, leading to regeneration of the aromatic diazonium salts. In cross-linked polystyrene, these decompose to yield nitrogen and, preferentially, radical-derived products. If the acidolysis of polystyrene-bound triazenes is conducted in the presence of hydrogen-atom donors (e.g. THF), unsubstituted arenes can be obtained (Entries 8 and 9, Table 3.47). In the presence of alkenes or alkynes and Pd(OAc)2, the initially formed diazonium salts undergo Heck reaction to yield vinylated or alkynylated arenes (Entry 10, Table 3.47). Similarly, unsubstituted arenes can be obtained by oxida-... 

Diazonium salts are important intermediates for the preparation of halides, and azo compounds. Diazonium salts can react as pseudohalide-type electrophiles, and can therefore be used in specific protocols for the Heck Reaction or Suzuki Coupling. 

Cleavage with an ensuing Heck reaction was developed by using the T1 triazene linker [51] (Scheme 6.1.20). On cleavage with trifluoroacetic acid a diazonium ion is first formed this can couple to an added alkene under the action of palladium catalysis. The coupling proceeds well with simple terminal alkenes, styrenes, and di- and even trisubstituted alkenes. The advantage of this process is clearly the possibility of using volatile alkenes (and alkynes) without contamination by any salt or other less volatile by-product, particularly with the use of palladium on charcoal as the catalyst. 

Because aryl diazonium salts are reasonably stable, other nucleophiles may be introduced to capture the aryl cation when the diazonium salt is heated. Among these, iodide ion is important as it allows the preparation of aryl iodides in good yield. These compounds are not so easy to make by electrophilic substitution (Chapter 22) as aryl chlorides or bromides because iodine is not reactive enough to attack benzene rings. Aryl iodides are useful in the more modern palladium chemistry of the Heck reaction, which you will meet in Chapter 48. 

The proposed mechanism for a standard Heck reaction is depicted in Scheme 6.5. Generally, a haloalkene or haloarene undergoes oxidative addition to an in situ generated, coordinatively unsaturated 14-electron palladium(O) complex, but other substrates such as tosylates, triflates or diazonium salts can also be applied. Subsequent, sy -insertion into the C=C double bond of a complexed olefin yields a t7-(j -alkenyl) or (j- aryl)alkylpalladium complex. If no hydrogen atom in a pseudo cis-position relative to the palladium is present, an internal rotation step is required prior to syw-elimination of the olefin to afford the traws-olefin product and a palladium(II) hydride complex. The latter is restored to the initial Pd(0) species by base-induced reductive elimination.137"401... 

Dimerisation, rather than the expected Heck coupling, took place in the reaction between styrene and arenediazonium salts in C4C im][PF6J to afford 1,3-diphenyl-1-butene.[25] Only catalytic amounts of the diazonium salt were required to trigger the reaction and their role in the reaction remain so far unclear. 

More recently, cationic intermediates have been observed in the Heck reactions of arene diazonium salts catalyzed by triolefinic macrocycle Pd(0) complexes [17,59], o-iodophenols and enoates to form new lactones [60], and o-iodophenols with olefins (the oxa-Heck reaction) [61 ]. In the first case ions were formed by oxidation of the analyte at the capillary, or by association of [NH4] or Na". In the two other cases ionization occurred through the more typical loss of a halide ligand. The oxa-Heck reaction provides a good example of how these experiments are typically performed and the type of information that can be obtained. The oxyarylations of olefins were performed in acetone, catalyzed by palladium, and required the presence of sodium carbonate as base. Samples from the reaction mixtures were diluted with acetonitrile and analyzed by ESI(+)-MS. Loss of iodide after oxidative addition of o-iodophenol to palladium afforded positively-charged intermediates. Species consistent with oxidative addition, such as [Pd(PPh3)2(C6H50)], and the formation of palladacycles of the type seen in Scheme 8 were observed. Based on this, a mechanism for the reaction was proposed (Scheme 8). 

Other leaving groups are effective in the oxidative addition with Pd , and can lead to efficient Heck reactions. An attractive possibihty is an aniline as starting material, with in situ generation of a diazonium salt. While the oxidation of the amino group can occur with Pd° alone at elevated temperatures, dehberate addition of t-butyl nitrite leads to... 

The Heck arylation of 2-substituted 3,4-dihydro-2//-pyrans with diazonium salts exhibits /ra 5-diastereoselectivity and leads to the 2-aryl-5,6-dihydro-27/-pyrans (Scheme 7) <03CC1656>. Tris(dihydropyranyl)indium undergoes Pd-mediated cross coupling reactions with aryl halides to give mainly 6-aryl-3,4-dihydro-2//-pyrans (Scheme 8) <030L2405>. 

The diazonium group can be replaced by a number of groups. " Some of these are nucleophilic substitutions, with S l mechanisms (p. 432), but others are free-radical reactions and are treated in Chapter 14. The solvent in all these reactions is usually water. With other solvents it has been shown that the Sj-jl mechanism is favored by solvents of low nucleophilicity, while those of high nucleophilicity favor free-radical mechanisms. The N2 group can be replaced by CP, Br, and CN, by a nucleophilic mechanism (see OS IV, 182), but the Sandmeyer reaction is much more useful (14-20). Transition metal catalyzed reactions are known involving aryl-diazonium salts, and diazonium variants of the Heck reaction (13-10) and Suzuki coupling (13-12) were discussed previously. As mentioned on p. 866 it must be... 

Although aryl and vinyl halides have found vast applications in Heck coupling, aromatic diazonium salts, particularly the isolable tetrafluoroborates, proved successful in the work of Kikukawa et al. [23 a, b] and a one-pot reaction with the C-C-coupling step [23 c-e]. Extensions of this tandem diazotation Heck reaction technique were reported by Beller et al. (eq. (5)) [23 f], including heterogeneous Pd/carbon catalysts [23 g]. 

Heck reactions are compatible with water (see Chapter 3.2.4) [35], which increases the speed of reaction in the presence of quaternary ammonium salts [36 a]. It is not surprising, then, that aqueous solvents (e. g. CH3CN/H2O) and water-soluble catalysts such as Pd(TPPTS)3 where TPPTS = P(C6H4-m-S03Na)3 [35, 67] can be employed successfully (eq. (10)). However, only aryl and vinyl iodides and aromatic diazonium salts (generated in situ from arylamines in aqueous media) are, up to the present, accessible to this method [36 b-h]. 

The Matsuda-Heck reaction of an aryl diazonium salt 82 with 1,1,1-trifluoropropene... 

In 1991 at the Central Research Laboratories of Hoechst AG we became interested in the palladium-catalyzed olefination (Heck reaction) of aryl halides and aryl diazonium compounds which is arguably one of the most powerfiil methods for the synthesis of substituted olefins. In collaboration with Herrmann and co-workers we have shown that active catalyst mixtures obtained by using in situ mixtures of Pd(II) salts and commercially available tri-o-tolylphosphine consist under the conditions of the Heck reaction primarily of cyclometaUated paUadacycles l... 

The Pd )-catalyzed reaction of aryl diazonium salts with mono-substituted alkenes [1] was found to be an interesting alternative to the well-known Pd - catalyzed arylhalide alkene coupling (Heck type reaction) or the copper mediated reaction of aryl diazonium salts with alkenes (Meerwein arylation) [2], The reaction can be run without isolation of the diazonium salt in presence of only 0.5 to 1 mol% of the Palladium catalyst in a one pot procedure, in high yield and under nuld conditions. The resulting styrene is reduced in a subsequent hydrogenation step with an in situ generated heterogeneous Pd-catalyst. The combination of three reaction steps without isolation of intermediates and the virtually complete recovery of the Pd-metal at the end of the reaction sequence makes this process [4] extremely efficient. 

Heck reaction. For this extremely valuable method of coupling unsaturated fragments, there are many variants with respect to substrate structures, additives, and reaction conditions. For instance, a solid-phase synthesis of styrenecarboxylic acids has been reported. The employment of diazonium salts in the Heck reaction is successful the presence of water does not seem to affect the efficiency (and in fact it was reported that water facilitates reactions of some other types of substrates). It is also possible to conduct the coupling in tandem with diazotization," which is carried out with BuONO-HOAc in CH2CI2 at room temperature. 

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