Heck cross coupling

Palladium-catalyzed Heck reactions are important in synthetic organic chemistry (253,254). Under conventional reaction conditions, a palladium black deposit was formed from the deterioration of the homogeneous palladium complex catalyst after the reaction. Recovery and recycle of the palladium catalyst are usually not realistic. 

In contrast, ionic liquids have been reported to be suitable solvents for Heck reactions because the products can be readily separated from the ionic liquids containing the homogeneous palladium catalysts. An early test with a palladium complex in ionic liquids showed remarkably improved recyclability of the catalyst (255), but palladium black still formed after several runs with recycled catalyst. 

When another palladium complex, diiodobis(l, 3-dimethylimidazolium-2-ylidene)palladium(II), was used as a catalyst (257), it resulted in a large improvement in catalyst stability in the same ionic liquid. The Heck reaction performed better in the ionic liquid than in organic solvents such as dimethylfuran (DMF). In the reaction of bromobenzene with styrene, the yield of stilbene was increased from 20% in DMF to 99% in [NBu4][Br]. The ionic liquid showed excellent solubility for all the reacting molecules. 

In experiments with a supported palladium catalyst, Pd/C, satisfactory yields were obtained without the use of phosphine ligands for the Heck reactions of aryl iodide with acrylonitrile, styrene, and methyl methacrylate in the ionic liquid [BMIM]PF6 (259). The addition of triethylamine improved the yields. The Pd/C remained in the ionic liquid only. The ionic liquid containing Pd/C can be reused as 

Okubo et al. (260) reported that Pd(II)/Si02 was a more effective catalyst than Pd/C when two equivalents of triethylamine base were added to the same ionic liquid one equivalent was not sufficient. The reaction was carried out without phosphine ligands. The unreduced Pd(II)/Si02 catalyst with two equivalents of base in [BMIM]PF6 was more active than the supported palladium catalysts in DMF. Furthermore, the stability of [BMIM]PF6 also improved with the addition of triethylamine. 

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Through the years, the development of transition metal-catalyzed methodologies, notably involving cyclotrimerization and Sonogashira or Heck cross coupling, has paved the way for rapid and efficient access to aryl glycoclusters with desired and controlled valency. 

Scheme 12. Pd(0)-catalyzed Sonogashira and Heck cross-coupling reactions leading to glycoclusters.100...

Meier MAR, FUali M, Gohy J-F, Schubert US (2006) Star-shaped block copolymer stabilized palladium nanoparticles for effident catalytic Heck cross-coupling reactions. J Mater Chem 16 3001-3006... 

Ruhland, B. Bombrun, A. Gallop, M. A. Solid-Phase Synthesis of 4-Ary-lazetidin-2-ones via Suzuki and Heck Cross-Coupling Reactions, J. Org. Chem. 1997, 62, 7820-7826. 

Applications of Suzuki and Heck cross-coupling reactions were adopted by Gallop and coworkers [131] to prepare diverse biaryl- and styryl-substituted (3-lactams on solid support. The catalyst system, [PdCl2(dppf)]-TEA, was found to be efficient to promote C-C bond formation around a (3-lactam template (Schemes 26 and 27). 

Wang, J.-X., Liu, Z., Hu, Y., Wei, B., Bai, L. Microwave-promoted palladium-catalyzed Heck cross-coupling reaction in water. J. Chem. 

After proof of concept with various reactions including, Suzuki-Miyaura cross coupling [20], Heck Cross coupling [20], Diels Alder reaction [20], Baylis Hillman reaction [20] and Grieco s 3-MCR [20, 121], the principle was applied to the synthesis of an antithrombotic in a sole solution of [bmim][PF6] [32] (Fig. 36). 

Scheme 2 Alkenylation via conventional Heck cross-coupling...

The Heck cross coupling reaction has been described with a phosphine-free PVK anchored palla-dium(II) complex as catalyst under aerobic conditions [57]. The Heck cross coupling reaction is shown in Figure 1.9. 

Various catalyst types were tested with a wide variety of substrates. For example, p-iodonitrobenzene and styrene react according to the Heck cross coupling to p-nitrostilbene with a yield of 99%. This situation is similar for many other reactions of styrene and methylacrylate with other reactants containing iodine and bromine. On the other hand, chlorobenzene reacts with styrene only in trace amounts. 

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