Cross-coupling reactions applications

Kalek M, Stawinski J. Synthetic studies on the P—C bond formation via a palladium-catalyzed cross-coupling reaction. Application to the synthesis of P-arylated nucleic acids. Collect. Symp. Ser. 2008 10 214-218. 

The preparation of perfluoroalkylzinc compounds has been achieved earlier 111 ethereal solvents [26] However, solvent effects play a significant role in the course of this reaction When a mixture of acetic anhydride and methylene chloride is used, coupled and cross-coupled products can be formed [27, 28] (equations 19 and 20) However, the cross-coupling reaction often gives mixtures, a fact that seriously restricts the synthetic applicability of this reaction [27, 28, 29]... 

In summary, palladium-mediated reactions, especially cross-coupling reactions have found many applications in quinoline synthesis. It is noteworthy that due to the a and S activation for the C(2) and C(4) positions, even 2-chloro- and 4-chloro-quinolines are viable substrates for palladium-catalyzed reactions under standard conditions. With the advent of the palladium chemistry and more commercially available organometallic substrates, more palladium-mediated quinoline syntheses are to be added to the repertoire of quinoline chemistry. 

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. 

For overviews of applications of the Heck reaction in natural products synthesis, see (a) Link, J. T. Overman, L. E. In Metal-Catalyzed Cross-Coupling Reactions, Diederich, F., Stang, P. J., Eds. Wiley-VCH New York, 1998 Chapter 6. (b) Brase, S. de Meijere, A. In Metal-Catalyzed Cross-Coupling Reactions Diederich, F., Stang, P. J., Eds. Wiley New York, 1998 Chapter 3.6. (c) Nicolaou, K. C. Sorensen, E. J. Classics in Total Synthesis VCH New York, 1996 Chapter 31. These authors refer to the Heck reaction as "one of the true "power tools" of contemporary organic synthesis" (p. 566). 

AT-acetyltryptamines could be obtained via microwave-assisted transition-metal-catalyzed reactions on resin bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide. While acceptable reaction conditions for the application of microwave irradiation have been identified for Stille heteroaryla-tion reactions, the related Suzuki protocol on the same substrate gave poor results, since at a constant power of 60 W, no full conversion (50-60%) of resin-bound 3-[2-(acetylamino)ethyl]-2-iodo-lH-indole-5-carboxamide could be obtained even when two consecutive cross-coupling reaction cycles (involving complete removal of reagents and by-products by washing off the resin) were used (Scheme 36). Also under conventional heating at 110 °C, and otherwise identical conditions, the Suzuki reactions proved to be difficult since two cross-coupling reaction cycles of 24 h had to be used to achieve full conversion. 

In summary, these results demonstrate that air-stable POPd, POPdl and POPd2 complexes can be directly employed to mediate the rate-limiting oxidative addition of unactivated aryl chlorides in the presence of bases, and that such processes can be incorporated into efficient catalytic cycles for a variety of cross-coupling reactions. Noteworthy are the efficiency for unactivated aryl chlorides simplicity of use, low cost, air- and moisture-stability, and ready accessibility of these complexes. Additional applications of these air-stable palladium complexes for catalysis are currently under investigation. 

This section gives a brief summary of the application of recyclable Pd(0) NP-IL catalyst systems in carbon-carbon cross-coupling reactions (Table 1.3, Scheme 1.3). More in-depth details and mechanistic aspects can be found in reviews of Pd(0) N P-catalyzed coupling reactions in ILs [129, 139, 140]. 

Simple Pd salts and complexes which contain neither phosphines nor any other deliberately added ligands are well known to provide catalytic activity in cross-coupling reactions. Such catalytic systems (often referred to as ligand-free catalysts ) often require the use of water as a component of the reaction medium.17 In the majority of cases such systems are applicable to electrophiles easily undergoing the oxidative addition (aryl iodides and activated bromides), although there are examples of effective reactions with unactivated substrates (electron-rich aiyl bromides, and some aryl chlorides).18,470... 

The synthesis and chemistry of pyrazoles, imidazoles, and 1,2,3-triazoles were actively pursued in 2006. A review on the cross-coupling reactions on azoles with two and more heteroatoms for pyrazoles and imidazoles has been published <06EJO3283>. Publications relating to 1,2,4-triazole and tetrazole chemistry were not particularly well represented this year. The solid-phase and combinatorial chemistry of these ring systems have not been investigated compared to past years. No attempt has been made to incorporate all the exciting chemistry or biological applications that have been published this year. 

This modification proved generally applicable and the Suzuki reaction is arguably the most versatile of modern cross-coupling reactions. The reaction has, for example, attracted the interest of groups involved in high-throughput chemistry, because a large variety of boronic acids are commercially available. 

Major advancements in the chemistry of pyrazoles, imidazoles, triazoles, tetrazoles, and related fused heterocyclic derivatives continued in 2000. Solid-phase combinatorial chemistry of pyrazoles and benzimidazoles has been particularly active. Synthetic routes to all areas continue to be pursued vigorously with improvements and applications. Notably, metal-promoted and cross-coupling reactions of all classes seemed to be a dominant theme in 2000. Applications of pyrazole-, imidazole-, and 1,2,3-benzotriazole-containing reagents to a wide array of synthetic applications remained active. 

Kotha S, Lahiri S, Kashinath D (2002) Recent applications of the Suzuki-Miyaura cross-coupling reaction in organic synthesis. Tetrahedron 58 9633-9695... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

Besides the above electrophiles, the acetylene—titanium complexes react regioselectively with other acetylenes providing the corresponding titanacyclopentadienes. An example of a homo-coupling reaction is shown in Eq. 9.11 [30], which also displays some synthetic applications [30,31]. Especially noteworthy is the highly regioselective cross-coupling reaction of unsymmetrical internal and terminal acetylenes, which is illustrated in Eq. 9.12... 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

Raboisson et al. <2002JOC8063> elaborated a new general approach to pyrazolo[l,5- ][l,3,5]triazine-based C-nucleosides 140 by application of palladium-mediated cross-coupling reaction. The reaction of 139 was carried out by using bis(dibenzylideneacetone)Pd(0), triphenylarsine, and triethylamine to give the product 140 in high yield (75%). 

Application in organic synthesis of pentacoordinated triorganodifluorosilicate anions, such as [Bu4N][Ph3SiF2] 825, have been extended to palladium(0)-catalyzed cross coupling reactions (solvents DMF, TFIF, dioxane) with arene halides (Scheme 111).825 This method is tolerant to various palladium(O) catalysts and provides excellent yields of mainly heterocoupled products and only small amounts of homocoupled byproducts. 

The cross-coupling reactions of allenes with components containing sp-carbon atoms are useful synthetic transformations since they provide yne-allenes and enyne-allenes, respectively. Due to the synthetic potential of these classes of carbon-rich unsaturated compounds, the scope and limitations were systematically investigated [1, 16-18]. The first synthetic application was reported in 1981, describing the preparation of alkynyl-substituted allenes by coupling of alkynylzinc chlorides with allenyl halides (Scheme 14.8) [11]. 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

This approach is applicable to cross-coupling reactions of allenoic acids and acrolein, which lead to the synthesis of lactones (Scheme 16.98) [104]. The reaction proceeds via oxypalladation of an allenoic acid to give rise to a vinylpalladium species. 

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