Halides, aryl base effect

The Heck reaction is a C-C coupling reaction where an unsaturated hydrocarbon or arene halide/triflate/sulfonate reacts with an alkene in presence of a base and Pd(0) catalyst so as to form a substituted alkene. Kaufmann et al. showed that the Heck reaction carried out in presence of ILs such as tetra-alkyl ammonium and phosphonium salts without the phosphine ligands, resulted in high yields of product. They attributed the activity to the stabilizing effect of ammonium and phosphonium salts on Pd(0) species. Carmichael et al. used ionic liquids containing either A,A -dialkylimidazolium and A-alkylpyridinium cations with anions such as halide, hexafluorophosphate or tetrafiuoroborate to carry out reactions of aryl halide and benzoic anhydride with ethyl and butyl acrylates in presence of Pd catalyst. An example of iodobenzene reacting with ethyl acrylate to give trans-et vy cinnamate is shown in Scheme 14. 

The reactivities of aryl halides, such as the halobenzenes, are exceedingly low toward nucleophilic reagents that normally effect displacements with alkyl halides and activated aryl halides. Substitutions do occur under forcing conditions of either high temperatures or very strong bases. For example, chlorobenzene reacts with sodium hydroxide solution at temperatures around 340° and this reaction was once an important commercial process for the production of benzenol (phenol) ... 

Aryl chlorides are more reluctant to participate in amination than most other aryl halides/pseudohalides. To tackle this problem, Caddick et al. examined the effect of palladium-N-heterocyclic carbenes as catalysts in rapid microwave-promoted reactions [87]. Para-tolyl and -anisyl chloride were reacted with aromatic and aliphatic amines in mostly good yields within 6 minutes of heating at 160 °C. Reactions using anisyl, tolyl or phenyl chlorides and aliphatic amines have also been reported by Maes et al. using a phosphine ligand and a strong base, which creates the desired products after 10 minutes of heating at 110-200 °C [88]. 

Sterically hindered alkylmonophosphines provided improved catalyst systems (Table 5) [163]. In this case, reactions occurred within 8 h at 100 °C for both activated and deactivated aryl bromides and with electron-poor or electron-neutral aryl chlorides. Reactions of ortho-substituted aryl halides were unusual, providing a mixture of 1- and 3-substituted indoles, but these aryl halides were suitable substrates when the 3-position of the indole was also substituted. The origin of this C- vs. N-arylation is unknown. The Tosoh group has also used this catalyst system for the arylation of the parent pyrrole, indole, and carbazole. They observed that Rb2C03 was a particularly effective base [187]. 

Various combinations of catalysts, bases, and solvents allow the biaryl coupling of arylboronic acids with aryl halides and triflates if there are no side-reactions such as the hydrolytic B-C bond cleavage or the participation of phosphine-bound aryls [4] (Scheme 29). The representative conditions are summarized in the scheme and the effects of catalysts and bases on yields and side reactions are discussed in sections 3.1 and 3.2. 

Based on mechanistic reasoning, the use of carbon monoxide or molybdenum hexacarbonyl as suitable CO sources necessitates of application of aryl halides. In addition, the effective concentration of CO in the reaction medium plays a crucial... 

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