Heck and Sonogashira Reaction

Palladium(0)-catalyzed coupling reactions - i. e. the Heck and Sonogashira reactions, the carbonylative coupling reactions, the Suzuki and Stille cross-coupling reactions, and allylic substitutions (Fig. 11.1) - have enabled the formation of many kinds of carbon-carbon attachments that were previously very difficult to make. These reactions are usually robust and occur in the presence of a wide variety of functional groups. The reactions are, furthermore, autocatalytic (i.e. the substrate regenerates the required oxidation state of the palladium) and a vast number of different ligands can be used to fine-tune the reactivity and selectivity of the reactions. 

Scheme 4.68 Heck and Sonogashira reactions applied in flow.

The moisture stability of the organostannanes and good functional group tolerance of the reaction make it most extensively used in coupling reactions. However, toxicity and low polarity of tin compounds are certain drawbacks of the use of the Stille reaction. The Suzuki coupling makes use of boronic acids and their derivatives, which is an improvement on the Stille coupling. In contrast to the Suzuki, Kumada, Heck and Sonogashira reactions which are carried out under basic conditions, the Stille reaction can be carried out under neutral conditions. 

In recent years, several natural products containing 2,4-disubstituted oxazoles have been isolated and their synthetic routes were investigated. Several key intermediates required for the synthesis of target compounds were achieved via the Stille, Suzuki, Heck, and Sonogashira reactions. In addition, several 2,5-diaryloxzoles were prepared from 2-halo-... 

Scheme 14 Ligand-free palladium-catalyzed Heck and Sonogashira reactions in the PASS-flow reactor (yields refer to purified products T5AA=tetrabutylammonium acetate NMP=i r-methylpyrrolidinone)...

An advantage of using polyisobutylene is solubility in a variety of nonpolar solvents at ambient temperatures. Also, the terminal double bond of polyisobutylene can be readily transformed into various useful groups for attachment of catalysts or reagents. Thus, polyisobutylene was used as a catalyst support for anchoring a sulfur-cation-sulfur Pd(ll), as shown above. These catalysts were used to perform allylic substitution, Heck, and Sonogashira reactions [26]. Polyisobutylene was also used to support chiral bisoxazoline ligands for copper-catalyzed cyclopropanation reactions [27]. Other uses... 

Ndjera C, Alonso DA (2008) Appheation of cyclopalladated compounds As catalysts for Heck and Sonogashira reactions. In Dupont J, Pfeffer M (eds) Palladacycles. Synthesis, characterization and appheations. Wiley-VCH, Weinheim, p 155... 

In 2008, Application of CyclopaUadated Compounds as Catalysts for Heck and Sonogashira Reactions, by Najera and Alonso [110], Palladacyclic Precatalysts for Suzuki Coupling, Buchwald-Hartwig Amination and Related Reactions Bedford [111]... 

Since aikenes and aikynes can be prepared via Heck and Sonogashira reactions, respectively, tandem processes are also possible for lactone synthesis [71-77]. Appropriately, o-iodobenzoic acids can generate both phthalide and isocoumarin derivatives under Pd catalysis, with a Cul co-catalyst favoring the former and... 

AU sorts oftriazene-linked haloarenes underwent the Heck and Sonogashira reactions without problems, but the Suzuki reactions failed with ortho-halo-substituted triazenes [591] (Scheme 8.83). 

Future avenues of research will focus on heterogeneous catalysis whereby highly active catalysts can be easily recycled and reused. Application has already begun in the established reactions such as Suzuki-Miyaura, Mizoroki-Heck and Sonogashira reactions. Over time it is expected that new C-H activation reactions will succumb to designed nanoparticle catalysis. Researchers in the field of total synthesis are... 

Singh B.K., Kaval N., Tomar S., Van der Eycken E., Parmar VS. Transition metal-catalyzed carbon-carbon bond formation Suzuki, Heck, and Sonogashira reactions using micro-wave and microtechnology. Org. Process Res. Dev. 2008 12 (3) 468 74. 

Stevens, P.D., Li, G.F., Fan, J.D., Yen, M. and Gao, Y. (2005) Recycling of homogeneous Pd catalysts using superparamagnetic nanoparticles as novel soluble supports for Suzuki, Heck, and Sonogashira cross-coupling reactions. Chemical Communications (35), 4435-4437. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Jutand, A. Dual role of nucleophiles in palladium-catalyzed Heck, Stille, and Sonogashira reactions. Pure Appl. Chem. 2004, 76, 565-576. Li, C.-J., Slaven, W. T., John, V. T., Banerjee, S. Palladium catalyzed polymerization of aryl diiodides with acetylene gas in aqueous medium a novel synthesis of areneethynylene polymers and oligomers. Chem. Commun. 1997,1569-1570. 

Erdelyi, M., Gogoll, A. Rapid Microwave Promoted Sonogashira Coupling Reactions on Solid Phase. J. Org. Chem. 2003, 68, 6431-6434. Najera, C., Gil-Molto, J., Karlstroem, S., Falvello, L. R. Di-2-pyridylmethylamine-Based Palladium Complexes as New Catalysts for Heck, Suzuki, and Sonogashira Reactions in Organic and Aqueous Solvents. Org. Lett. 2003, 5,1451-1454. 

During the last 30 years, numerous books, monographs, and reviews have been published on organo-palladium chemistry and palladium-catalyzed reactions such as the Heck, Suzuki, Stille, and Sonogashira reactions [1-52], These represent well-established methods for carbon—carbon bond formation in organic synthesis. 

However, the real breakthrough in this area is due to the development of catalysis by transition metals, with the Heck, Suzuki, Sonogashira reactions and other related coupling process. ... 

Polystyrene-supported soluble palladacycle catalyst as recyclable catalyst for Heck, Suzuki and Sonogashira reactions... 

A new type of soluble polystyrene-supported palladium complex was synthesised (Figure 6.1) as an excellent and recyclable palladacycle catalyst for carbon-carbon bond formation in Heck, Suzuki and Sonogashira reactions to give high yields of the desired products. 

The newly invented polystyrene-supported palladacycle catalyst was prepared in six steps with high yields. The simple precipitation and filtration process to recycle the catalyst after model reactions for Heck, Suzuki, and Sonogashira reactions is noteworthy.[1]... 

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