Palladium-catalysed cross-coupling reactions

The application of organozinc iodides prepared in THF is illustrated in Protocols 4 and 5, which describe the palladium catalysed cross-coupling of a serine-derived organozinc iodide with a vinyl iodide, and the palladium catalysed carbonylative cross-coupling of another serine-derived organozinc iodide with a functionalized aromatic iodide. In the reaction with the vinyl iodide, it is important to transfer the solution of the organozinc iodide from the residual zinc, since this can react unproductively with the electrophile. In the case of the carbonylative coupling with the functionalized aromatic iodide, such a transfer is unnecessary, since the zinc does not react with the electrophile under the reaction conditions. These two protocols also illustrate how to conduct such reactions on different scales. 

The Aspidosperma alkaloids are a group of more than 100 monomeric and dimeric monoterpene indole alkaloids with aspidospermidine (228) representing a key member of the class and sometimes considered to be the parent [68]. Numerous total syntheses of this pentacyclic compound have been reported. Our own contributions in the area were prompted by the discovery of a new method for preparing indoles via a palladium-catalysed Ullmann cross-coupling reaction that proceeds especially efficiently at close to room temperature [69] and which we felt could serve as the centrepiece in developing a new synthesis of compound 228 and, in the longer term, syntheses of dimeric members of the indole alkaloid class such as the clinically significant alkaloids vinblastine and vincristine. 

The Grignard reagents are far more applicable counterparts in the nickel- and palladium-catalysed Kharasch cross-coupling reactions with aryl halides (1, Br, Cl), as well as aryl triflatcs, to give biaryls in moderate to excellent yields [19]. In early... 

Mathews, C.J., Smith, P.J., and Welton, T. (2000) Palladium catalysed Suzuki cross-coupling reactions in ambient temperature ionic liquids. Chem. Commun., 1249 1250. 

Marsh, K.N., Boxall, J.A. lichtenthaler, R. (2004). Room Temperature Ionic Liquids and Their Mixtures, a Review, Fluid Phase EquUtb., pp. 219, 93-98 Mathews, C.J., Smith, P.J. Welton, T. (2000). Palladium Catalysed Suzuki Cross-Coupling Reactions in Ambient Temperature Ionic Liquids, Chem. Commun., 14, pp. 1249-1250 McNulty, J., Capretta, A., Wilson, J., Dyck, J., Adjabeng, G. Robertson, A. (2002). Suzuki Cross-Coupling Reactions of Aryl Halides in Phosphonium Salt Ionic Liquid imder Mild Conditions, Chem, Commun., 17, pp. 1986-1987 McLachlan, F., Mathews, C.J., Smith, P.J. Welton, T. (2003). Palladium-Catalyzed Suzuki Cross-Coupling Reactions in Ambient Temperature Ionic Liquids Evidence for the Importance of Palladium Imidazolylidene Complexes, Organometallics, 22, pp. 5350-5357... 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

With palladium catalysts aromatic chlorides are rather unreactive, however, nickel is able to catalyze the reactions of these substrates, too. The water-soluble catalyst was generated in situ from the easily available [NiCl2(DPPE)] and an excess of TPPTS by reduction with Zn in mixtures of 1,4-dioxane and water. Although it had to be used in relatively large quantities (10 mol %), the resulting compound catalysed the cross-coupling... 

Palladium catalysts have been found which are effective in the Suzuki coupling reaction of arylboronic acids with aryl chlorides carrying electron-withdrawing groups.73 Biaryls may also be synthesized by cross-coupling of arylboronic acids with arenediazonium salts.74,75 There has been a report of the polymer-bound palladium-catalysed Suzuki coupling of aryl triflates with organoboron compounds.76 Arylbor-onates may themselves be synthesized by the palladium-catalysed reactions of... 

However, for other palladium catalysed reactions of organozinc iodides with electrophiles, THF is a good choice of solvent. The incompatibility of THF and acid chlorides at ambient temperature can also be overcome, in some cases, by the use of a carbonylative cross-coupling in which an iodobenzene derivative is used as the precursor.17... 

Aryltrimethoxysilanes, for use in cross couplings, can be prepared by a palladium-catalysed reaction of aryl iodides with trimethoxysilane, but this silane is extremely toxic ... 

In domino transition-metal-catalysed processes, cross-coupling reactions can also be nsed as the starting transformation. Most often, Suzuki, Stille and Sonogashira reactions are employed in this context. They can be combined with a Mizoroki-Heck reaction and other palladium-catalysed transformations. 

Banwell MG, Lupton DW. Exploiting the palladium[0]-catalysed Ullmann cross-coupling reaction in natural products chemistry apphcation to a total synthesis of the alkaloid ( )-aspidospermidine. Org. Biomol Chem. 2005 3(2) 213 15. 

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