Palladium-catalyzed reactions Heck reaction

Bisacid 91 was used toward three different targets. For the first, a palladium-catalyzed decarboxylative Heck reaction followed by perylenequinone formation provided bis-styryl derivative 92 (Scheme 7.22) [52]. For the second, the C5,C5 -benzyl ethers were cleaved, and the more acidic carboxylic acids were then selectively benzylated using BnBr and K2CO3 (Scheme 7.22). This re-esterification... 

A novel approach towards the construction of the morphine skeleton is demonstrated by the total synthesis of ( )-desoxycodeine-D. One of the key steps for this synthesis is the palladium-catalyzed intramolecular Heck reaction. Therefore, this synthetic strategy for the construction of the polycyclic ring systems has provided an efficient access to the complete pentacyclic skeleton of morphine <00TL915>. 

It has been proven that palladium catalyzed reductive Heck reactions are versatile and high-yield approach for preparing of new bioactive alkaloid epibatidine (1) analognes fromN-benzoylated 2-aza-bicyclo[2.2.1]hept-5-ene (3) and it has been shown that in case of aryl- groups reaction progresses regioselectively. All Heck type reactions proceed exo-selectively, leading to the same stereochemistry as fonnd in 1. 

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... 

It is worth noting that the diastereoselectivity of these direct arylations turned out to be complementary to palladium-catalyzed Mizoroki-Heck reactions (Scheme 25). 

Both decks of the [2.2]paracyclophane derivatives 160 and 161 could be transformed into 1,4-distyrylbenzene chromophores via the palladium-catalyzed coupling (Heck reaction) with styrene and substituted styrenes adopting the protocol of Jeffery [106]. The fourfold coupling products 162 and 163 were thus obtained with yields up to 70% [107a]. As four new carbon-carbon bonds are formed in this transformation, each single coupling step must proceed with excellent yield. All these reactions lead stereoselectively to products with (E)-configurated double bonds. 

Haneda, S., Ueba, C., Eda, K. and Hayashi, M. (2007) Imidazole and imidazoline derivatives as IV-donor ligands for palladium-catalyzed Mizoroki-Heck reaction. Adv. Synth. Catal., 349, 833-5. 

Mino, T., Shirae, Y, Sasai, Y. et al. (2006) Phosphine-free palladium catalyzed Mizoroki-Heck reaction using hydrazone as a ligand. J. Org. Chem., 71, 6834—9. 

Hashimoto, Y, Horie, Y, Hayashi, M. and Saigo, K. (2000) An efficient phosphorus-containing oxazoline ligand derived from cw-2-amino-3,3-dimethyl-l -indanol application to the palladium-catalyzed asymmetric Heck reaction. Tetrahedron Asymmetry, 11, 2205-10. 

Scheme 7.4 Palladium-catalyzed carbonylative Heck reaction to quinolinones...

Shortly thereafter, a more general palladium-catalyzed carbonylative Heck reaction of aryl halides was able to be developed by our group [34]. For the first time, various aromatic and aliphatic alkenes were used successfully in this system, and good yields of the corresponding a,jS-unsaturated ketones were obtained (41-90 %). Starting from easily available aryl iodides and bromides, interesting building blocks were obtained under mild conditions (Scheme 7.15). With respect to the reaction mechanism, the aryl palladium complex and acyl palladium complex were characterized by X-ray, and the mechanism was studied step by step. The results fit well with DFT calculations. 

Scheme 7.15 Palladium-catalyzed carbonylative Heck reaction of aryl halides...

In 2011, Palladium-Catalyzed Oxidation Heck Reactions, by Su and Jiao [102]. Recent Advances in Sonogashira Reactions, by Chinchilla and Najera [112]. Nanocatalysts for Suzuki Cross-Coupling reactions, by Fihri, Bouhrara, Nekoueishahraki, Basset, and Polshettiwar [113]... 

More recently, a much milder and highly efficient approach has been developed by Komiyama in Japan that applies palladium-catalyzed heteroaryl Heck reaction to access key intermediate 31 from bromoarene 44 and thiazole 45. After intense screening of palladium precatalysts, base, solvent, ligand, co-catalyst Cu(l) salts, and organic acid... 

Sun synthesized 2-substituted indoles via a palladium-catalyzed domino Heck reaction and dealkylation from 59 to 60. The method was optimized by applying varietity of catalysts and solvents, resulting in Pd(OAc)2 and DMSO at 110-130 °C with high yields. ... 

SCHEME 63 Palladium-catalyzed domino Heck reaction/C—H functionalization. 

SCHEME 6.4 Palladium-catalyzed tandem Heck reaction/C-H activation. 

Felpin et al. developed a palladium-catalyzed tandem Heck reaction-reduction-cyclization synthesis of oxindoles (n=0) and dihydroquinolones (n= 1) using different 2-(2-nitrophenyl)aaylates (n=0) or 2-(2-nitrobenzyl)aaylates (n=l) and aryldiazonium salts 36 in good yield [15] (Scheme 6.7). However, a complementary approach was developed by the same group using diazonium salts 40 and substituted acrylates 41 to access a larger substitution pattern on the C3 position (Scheme 6.8). It is noteworthy that a different solvent was required and the charcoal had to be added after the Heck reaction. C3-unsubstituted, arylated, and alkylated dihydroquinolones 42 can be obtained efficiently using this protocol. 

Szlosek-Pinaud et al. developed a very simple and efficient method for the preparation of a wide range of functionalized 3,3-disubstituted-2,3-dihydrobenzofurans 64 via palladium-catalyzed tandem Heck reaction/Suzuki cross-coupling [24] (Scheme 6.15). 

SCHEME 6.69 Palladium-catalyzed chloropalladation/Heck reaction cascade. 

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

The double-Heck-approach can also be employed for the preparation of novel heterocyclic compounds as 6/1-25 and 6/1-26 (Scheme 6/1.4) [24]. Thus, the palladium-catalyzed reaction of 6/1-21 and the cyclic enamide 6/1-22 gave a Oil-mixture of 6/1-23 and 6/1-24, which in a second Heck reaction using the palladacene 6/1-15 led to 6/1-25 and 6/1-26 in an overall yield of 44—49%. The synthesis can also be performed as a domino process using a mixture of Pd(OAc)2 and the palladacene 6/1-15. 

It is well known that minor changes in conditions can have dramatic effects on the products obtained. For example, Heck s group [31] described the palladium-catalyzed reaction of iodobenzene 6/1-42 and 2 equiv. of diphenylacetylene 6/1-43 in... 

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