Arenes Mizoroki-Heck reaction

Still, there are base-free Mizoroki-Heck reactions, which are known to occur with arene diazonium salts. In this particular case, the absence of base is advantageous, as spontaneous decomposition of diazonium salts is known to be accelerated by nucleophiles and bases. High precatalyst loadings are required, as, for example, in the arylation of disubstited acrylates 10 (9 11, Scheme 2.2) [10] a base-free reaction might only be sustained for a few turnovers. 

The first waste-free vinylation of arenes under C—H activation is as old as the Mizoroki-Heck reaction itself already in 1967, Moritani and Fujiwara [6] revealed a stoichiometric reaction of styrene-palladium(II) chloride dimers with benzene in the presence of acetic acid to give stilbenes in a modest 24% yield. During this process, the palladium(II) precursor is reduced to palladium(O), so that the key to closing the catalytic cycle was to add an efficient reoxidation step to regenerate an active palladium(II) species. One year later, the same group presented a first approach, substoichiometric in palladium. 

This concept was proven to be viable using the example of 4-nitrophenyl esters in the presence of a palladium(II) chloride/lithium chloride/isoquinoline catalyst system, the 4-nitrophenyl esters 3c of various aromatic, heteroaromatic and vinylic carboxylic acids were converted to the corresponding vinyl arenes 5k along with 4-nitrophenol (Figure 4.17). The latter was demonstrated to react with benzoic acid at the same temperature as required for the vinylation step (160 °C) to regenerate the corresponding ester [28], thus demonstrating that at least a two-step waste-minimized Mizoroki-Heck reaction is feasible. 

Furthermore, Kiindig et al. [26] investigated intramolecular Mizoroki-Heck reactions at planar chiral arene tricarbonyl chromium complexes 29a—c, giving indanes substituted in the benzylic position in good yield (80% for = Me, 78% for = OH and 85% for R = OMe) (29a—c 30a—c. Scheme 5.5). 

A combination of a Mizoroki-Heck reaction and a C—N coupling on solid phase was reported by Yamazaki et al. [105] in the synthesis of indole carboxylate 197 employing immobilized A-acetyldehydroalanine (194) and a bifunctionalized arene 195. In these transformations, 196 is the intermediate. The best results were obtained with o-dibromoarenes such as 195b and 195d using the Pd2(dba)3/P-r-Bu3/Cy2NMe catalytic system developed by Littke and Fu [106]. The protocol was also extended to the synthesis of isoquinolines [107] (Scheme 8.50). 

Kamikawa, K., Harada, K. and Uemura, M. (2005) Catalytic asymmetric induction of planar chirality palladium catalyzed intramolecular Mizoroki-Heck reaction of prochiral (arene)chromium complexes. Tetrahedron Asymmetry, 16, 1419-23. 

A key step of the total synthesis of lily-of-the-valley fragrance )8-LiUal (3-(4-terr-butylphenyl)-2-methylpropanal, 17) is a Mizoroki-Heck reaction of arene iodide 15 with allyl alcohol 16 leading to the carbonyl product (Scheme 15.5) [51]. 

Scheme 7.50 Intramolecular oxidative Mizoroki-Heck reaction of electron-rich arenes.

As general synthetic methods for alkenyl halides have been developed [64], the inverse Mizoroki- Heck reactions between (hetero)arene C- H bonds and alkenyl halides may be recognized to be one of the practical approaches toward aUceny-larenes and alkenyl heteroarenes. 

Pd catalysts also promote the decarbonylative Mizoroki-Heck reactions of even poorly reactive p-nitrophenyl aryl carboxylates with olefins to give the vinyl arenes in good to excellent yields, along with CO and the corresponding phenols [40]. Mizoroki-Heck-type arylation of styrene and acrylate esters by use of aroyl chlorides can also be performed in the presence of PdCljlPhCN) / (PhCHjlBUjNCl as the catalytic system without adding base [41]. 

Silver(I) carbonate was the best choice for oxidant, outperforming AgOAc. Pivalic acid was utilized as an additive. Different arenes could be employed, providing separable mixtures of arylated and diarylated products. The resulting products were converted to phenanthroline derivatives and tested in transition metal-free direct arylation and Mizoroki-Heck reactions. 

Rh-Catalyzed Reactions Zhao and coworkers have shown that the reaction of ortho-substituted arene carboxylic acids with electron-deficient olefins in the presence of ahydrorhodium(I) complex as the catalyst gave the Mizoroki-Heck products (8) and the conjugate addition products (9) with high selectivity (Scheme 22.18a) [13, 26]. The selectivity depends on the content of water in the reaction mixture higher water content favored the hydrolysis of the enolato intermediate 10, while lower water content favored P-H elimination. This reaction works only for ortho-suhstituted arene carboxylic acids and with electron-deficient olefins (Scheme 22.18h). 

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