Heck reaction recent developments

The palladium-catalyzed C-C coupling between aryl halides or vinyl halides and activated alkenes in the presence of a base is referred as the Heck Reaction . Recent developments in the catalysts and reaction conditions have resulted in a much broader range of donors and acceptors being amenable to the Heck Reaction. 

Palladacycles [17] have been established as important class of catalysts, an unusual phosphine-free sulfur containing catalyst was introduced by Zim [18] et al. A phosphinite based palladacycle [19] proved to be very efficient in Suzuki coupling reactions. An N,P-Ligand type was synthesized by Kocovsky [20] et al. Tridentate pincer ligands [21] have been proved use-fill in the Heck reaction. Recent developments regarding Heck (22] and Suzuki [23] reactions have been reviewed by Fu and Littke. A new catalyst especially suitable for Heck couplings has been introduced by Beller [24] et al. 

The Asymmetric Heck Reaction Recent Developments and Applications of New Palladium Diphenylphosphino-pyrrolidine Complexes. 

Arylations with the Heck-Matsuda Reaction - Recent Developments... 

Recent Developments and New Perspectives In The Heck Reaction," Cabri. W. Candiani, T. Accts. Chem. Res., 1995, 28, 2... 

Very recently, Dongol and coworker have developed a one-pot synthesis of isoxa-zolidinones starting from O-homoallyl hydroxylamines and aryl halides. After a Heck reaction of the substrates, a subsequent C-N bond formation took place to furnish the target compounds in up to 79% yield [86]. 

In the Heck reactions discussed above it was essential to use polar aprotic solvents such as acetonitrile or DMF if high regioselectivity was to be achieved. In other Heck couplings the use of water as a solvent has recently gained attention. The advantages of water compared with standard organic solvents are many - it is, for example, cheap and nontoxic - but its usefulness extends only over a number of well-defined applications, partly because of problems with the solubility of the reactants and catalysts. The development of aqueous catalytic systems is, consequently, an important field [21]. 

Knoke and de Meijere [60] recently developed a highly flexible domino Heck-Diels-Alder reaction of a symmetrically substituted cumulene 125, which also involves cross-couplings of an allene at the central position. Both aryl and hetaryl halides react efficiently with l,3-dicyclopropyl-l,2-propadiene (125) and furnish 1,3,5-hexatriene derivatives 126 as intermediates, which are usually trapped by acceptor-substituted olefins in a subsequent cycloaddition, providing adducts 127a/b in moderate to good overall yields (Scheme 14.30). 

Palladium(0)-catalyzed cross-coupling of aryl halides and alkenes (i.e., the Heck reaction) is widely used in organic chemistry. Oxidative Heck reactions can be achieved by forming the Pd -aryl intermediate via direct palladation of an arene C - H bond. Intramolecular reactions of this type were described in Sect. 4.1.2, but considerable effort has also been directed toward the development of intermolecular reactions. Early examples by Fu-jiwara and others used organic peroxides and related oxidants to promote catalytic turnover [182-184]. This section will highlight several recent examples that use BQ or dioxygen as the stoichiometric oxidant. 

Cabri, W. and Candiani, I., Recent developments and new perspectives in the Heck reaction, Acc. Chem. Res.,... 

Recent development of the Heck reaction has also led to greater understanding of its mechanistic details. The general outlines of the mechanism of the Heck reaction have been appreciated since the 1970s and are discussed in numerous reviews [2,3]. More recently, two distinct pathways, termed the neutral and cationic pathways, have been recognized [2c-g,3,7,8,9]. The neutral pathway is followed for unsaturated halide substrates and is outlined in Scheme 8G. 1 for the Heck cyclization of an aryl halide. Thus, oxidative addition of the aryl halide 1.2 to a (bisphosphine)Pd(O) (1.1) catalyst generates intermediate 1.3. Coordination of... 

The term Heck reaction is associated with such a huge variety of transformations that it is impossible to cover them all within the scope of this chapter. We therefore restricted ourselves to giving an outline of the reaction principle and discussing a number of illustrative developments in this exciting field of research. For a more comprehensive overview, we recommend recent review articles [6-8],... 

G. T. Crisp, Variations on a Theme Recent Developments on the Mechanism of the Heck Reaction and Their Implications for Synthesis, Chem. Soc. Rev. 1998, 27, 427 136. 

Seminal contributions to the development of asymmetric cyclic Heck reaction were made in 1989 by Overman [72] and Shibasaki [73]. These and other groups have since developed the reaction as a useful tool for asymmetric synthesis of complex natural products as indicated by representative examples shown in Schemes 20 [74-76] and 21 [77-79]. For further details, the readers are referred to recent reviews [43,57]. 

Other palladium acetylacetonate complexes have also been developed for cross-coupling reactions. Indeed, an acac paUadacycle complex has recently been observed to effectively catalyze both the Suzuki-Miyaura and Heck reactions. Likewise, the A-heterocyclic carbene complex Pd(acac)Cl(ipr) (96) is an excellent catalyst for the formation of C—N and C—C bonds (equation 27) These catalysts were effective for coupling of ketones... 

The intramolecular Heck cyclizations highlighted in this chapter were typically conducted with 5-20 mol% of a palladium catalyst. In few, if any, of these studies were catalyst loadings and cyclization conditions carefully optimized. As a result, we have not included catalyst loadings in the schemes in this chapter. Only recently has serious attention been directed to optimizing catalyst turnover in Heck reactions and to the development of more robust catalyst systems. It seems likely that in the future many Heck cyclizations will be accomplished with catalyst loads of 1 % or lower [76]. 

The development of new catalysts for Heck arylations of unactivated aryl chloride substrates has also been a recent focus of research in this area. In late 1990s, Reetz [75] and Fu [76] successfidly conducted intermolecular Heck reactions using aryl chlorides as substrates, as exemplified by the conversion of p-chloroanisole to adduct 78 [76], A few examples of Heck reactions involving unactivated heteroaryl chlorides have also been described [77],... 

Muller and coworkers have recently developed a coupling-isomerization reaction, initially identified as a side reaction which occurred under standard Sonogashira conditions [79]. As demonstrated below, the coupling reaction is followed by a shuffling of oxidation states via an alkyne-allene isomerization [80]. The product, a,P-unsaturated ketone 146, is reminiscent of a product which would be obtained from a Heck reaction. The utility of this reaction was further demonstrated when diamine 147 was added to the reaction pot. Following a conjugate addition reaction and imine formation, compound 148 resulted from the three-component, one-pot reaction sequence enabled by the coupling-isomerization reaction. 

Scope and limitations of the Heck reaction synthesis of dienes The Heck reaction with electron-rich alkenes A synthesis of strychnine Recent developments in the Heck reaction Sp2-sp2 Cross-Coupling Reactions by Transmetallation Stille coupling... 

Rapid development in the Heck reaction has made it one of the most important of all modem methods. A dramatic example is a recent synthesis of strychnine by M. Nakanishi and M. Mori.23 This synthesis illustrates the intramolecular Heck reaction particularly well, showing examples of regioselectivity in attack on the alkene and in formation of the new alkene. The synthesis starts with a Heck reaction on enantiomerically pure 149. Attack occurs on the nearer end of the alkene to give 150 that cannot eliminate to reform the same alkene as there are no H atoms left and the alkene 151 must be formed. The stereochemistry is controlled by the short tether linking the aryl bromide and the alkene. 

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