Ligand effects Heck reactions

Schmidt, A.R, Al-Halaiqa, A. and Smirnov, V.V. (2006) Effect of macrokinetic factors on the ligand-free Heck reaction with non-activated bromoarenes. J. Mol. Cat. A Chem., 250, 131-7. 

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. 

Another particularly attractive substrate class for industrial Heck reactions are the arenediazonium salts, because of to their ready availability from anilines. Matsuda et al. found that for these highly reactive compounds, ligand-free Pd(dba)2 suffices as catalyst [32], Even palladium catalysts on solid supports are highly effective [33], The diazotization of an aniline 25 and its olefination can be performed separately, or in one pot (Scheme 12). 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

The enantioselective Heck reaction has matured into a powerful method for asymmetric C-C bond formation and has proven its value in several total syntheses. One can expect that it will find many more applications in the future, even in industry. There is still an extensive space for chemists to design new suitable substrates and to search for new effective chiral ligands [23]. 

Bulky ligands as above have also proved to be effective in other palladium-catalyzed reactions of aryl halides, e.g., amination [16-19], Suzuki-Miyaura reaction [20-22], Mizoroki-Heck reaction [23, 24], Migita-Kosugi-Stille reaction [25], and aryloxylation and alkoxylation [26-28] as well as the reaction with various carbon nucleophiles as described below. The ligands are considered to enhance both the initial oxidative addition of aryl halides and the reductive elimination of products [29, 30]. The effectiveness of the commercially available simple ligand, P(f-Bu)3, was first described for the amination by Nishiyama et al. [16]. 

The remarkable affinity of the silver ion for hahdes can be conveniently applied to accelerate the chiral palladium-catalyzed Heck reaction and other reactions. Enantioselectivity of these reactions is generally increased by addition of silver salts, and hence silver(I) compounds in combination with chiral ligands hold much promise as chiral Lewis acid catalysts for asymmetric synthesis. Employing the BINAP-silver(I) complex (8) as a chiral catalyst, the enantioselective aldol addition of tributyltin enolates (9) to aldehydes (10) has been developed." This catalyst is also effective in the promotion of enantioselective allylation, Mannich, ene, and hetero Diels-Alder reactions. 

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